It’s time to develop alternatives to antibiotics for small infections, according to a new thought paper by scientists at the Georgia Institute of Technology, and to do so quickly.

It has been widely reported that bacteria will evolve to render antibiotics mostly ineffective against them by mid-century, and current strategies to make up for the projected shortfalls haven’t worked.

One possible problem is that drug development strategies have focused on replacing antibiotics in extreme infections, such as sepsis, where every minute without an effective drug increases the risk of death.

But the evolutionary process that brings forth antibiotic resistance doesn’t happen nearly as often in those big infections as it does in the multitude of small ones like sinusitis, tonsillitis, bronchitis, and bladder infections, the Georgia Tech researchers said.

“Antibiotic prescriptions against those smaller ailments account for about 90 percent of antibiotic use, and so are likely to be the major driver of resistance evolution,” said Sam Brown, an associate professor in Georgia Tech’s School of Biological Sciences. Bacteria that survive these many small battles against antibiotics grow in strength and numbers to become formidable armies in big infections, like those that strike after surgery.

“It might make more sense to give antibiotics less often and preserve their effectiveness for when they’re really needed. And develop alternate treatments for the small infections,” Brown said.

Brown, who specializes in the evolution of microbes and in bacterial virulence, and first author Kristofer Wollein Waldetoft, a medical doctor and postdoctoral research assistant in Brown’s lab, published an essay detailing their suggestion for refocusing the development of bacteria-fighting drugs on December 28, 2017, in the journal PLOS Biology.

Duplicitous antibiotics

The evolution of antibiotic resistance can be downright two-faced.

“If you or your kid go to the doctor with an upper respiratory infection, you often get amoxicillin, which is a relatively broad-spectrum antibiotic,” Brown said. “So, it kills not only strep but also a lot of other bacteria, including in places like the digestive tract, and that has quite broad impacts.”

E. coli is widespread in the human gut, and some strains secrete enzymes that thwart antibiotics, while other strains don’t. A broad-spectrum antibiotic can kill off more of the vulnerable, less dangerous bacteria, leaving the more dangerous and robust bacteria to propagate.

“You take an antibiotic to go after that thing in your throat, and you end up with gut bacteria that are super-resistant,” Brown said. “Then later, if you have to have surgery, you have a problem. Or you give that resistant E. coli to an elderly relative.”

Much too often, superbugs have made their way into hospitals in someone’s intestines, where they had evolved high resistance through years of occasional treatment with antibiotics for small infections. Then those bacteria have infected patients with weak immune systems.

Furious infections have ensued, essentially invulnerable to antibiotics, followed by sepsis and death.

Alternatives get an “F”

Drug developers facing dwindling antibiotic effectiveness against evolved bacteria have looked for multiple alternate treatments. The focus has often been to find some new class of drug that works as well as or better than antibiotics, but so far, nothing has, Brown said.

Wollein Waldetoft came across a research paper in the medical journal Lancet Infectious Diseases that examined study after study on such alternate treatments against big, deadly infections.

“It was a kind of scorecard, and it was almost uniformly negative,” Brown said. “These alternate therapies, such as phage or anti-virulence drugs or, bacteriocins -- you name it -- just didn’t rise to the same bar of efficacy that existing antibiotics did.”

“It was a type of doom and gloom paper that said once the antibiotics are gone, we’re in trouble,” Brown said. “Drug companies still are investing in alternate drug research, because it has gotten very, very hard to develop new effective antibiotics. We don’t have a lot of other options.”

But the focus on new treatments for extreme infections has bothered the researchers because the main arena where the vast portion of resistance evolution occurs is in small infections. “We felt like there was a disconnect going on here,” Brown said.

Don’t kill strep, beat it

The researchers proposed a different approach: “Take the easier tasks, like sore throats, off of antibiotics and reserve antibiotics for these really serious conditions.”

Developing non-antibiotic therapies for strep throat, bladder infections, and bronchitis could prove easier, thus encouraging pharmaceutical investment and research.

For example, one particular kind of strep bacteria, group A streptococci, is responsible for the vast majority of bacterial upper respiratory infections. People often carry it without it breaking out.

Strep bacteria secrete compounds that promote inflammation and bacterial spread. If an anti-virulence drug could fight the secretions, the drug could knock back the strep into being present but not sickening.

Brown cautioned that strep infection can lead to rheumatic heart disease, a deadly condition that is very rare in the industrialized world, but it still takes a toll in other parts of the world. “A less powerful drug can be good enough if you don’t have serious strep throat issues in your medical history,” he said.

Sometimes, all it takes is some push-back against virulent bacteria until the body’s immune system can take care of it. Developing a spray-on treatment with bacteriophages, viruses that attack bacteria, might possibly do the trick.

If doctors had enough alternatives to antibiotics for the multitude of small infections they treat, they could help preserve antibiotic effectiveness longer for the far less common but much more deadly infections, for which they’re most needed.

Want to Learn More? Read: FDA Taps Georgia Tech to Help Reduce Cost of Making Antibiotics

Research was funded by the Simons Foundation (grant 396001), the Centers for Disease Control and Prevention (grant OADS-2016-N-17812), the Wenner-Gren Foundation, and the Physiographic Society of Lund. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsors.

In the solution-based process, precursor chemicals adsorb to nanocrystal seeds before being reduced to atoms that fuel growth of the nanocrystals. The kinetics data is based on painstaking systematic studies done to determine growth rates on different nanocrystal facets — surface structures that control how the crystals grow by attracting individual atoms. 

In an article published December 11 in the journal Proceedings of the National Academy of Sciences, a research team from the Georgia Institute of Technology provided a quantitative picture of how surface conditions controlled the growth of palladium nanocrystals. The work, which will later include information on nanocrystals made from other noble metals, is supported by the National Science Foundation.

“This is a fundamental study of how catalytic nanocrystals grow from tiny seeds, and a lot of people working in this field could benefit from the systematic, quantitative information we have developed,” said Younan Xia, professor and Brock Family Chair in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We expect that this work will help researchers control the morphology of nanocrystals that are needed for many different applications.”

A critical factor controlling how nanocrystals grow from tiny seeds is the surface energy of the crystalline facets on the seeds. Researchers have known that energy barriers dictate the surface attraction for precursors in solution, but specific information on the energy barrier for each type of facet had not been readily available.

“Typically, the surface of the seeds that are used to grow these nanocrystals has not been homogenous,” explained Xia, who is also the Georgia Research Alliance Eminent Scholar in Nanomedicine and holds joint appointments in School of Chemistry & Biochemistry and School of Chemical & Biomolecular Engineering. “You may have different facets on the crystals, which depend on the arrangement of the atoms below them. From the standpoint of precursors in the solution around the seeds, these surfaces have different activation energies which determine how difficult it will be for the precursors or atoms to land on each surface.”

Xia’s research team designed experiments to assess the energy barriers on various facets, using seeds in a variety of sizes and surface configurations chosen to have only one type of facet. The researchers measured both the growth of the nanocrystals in solution and the change in concentration of palladium tetrabromide (PdBr₄ ^2-) precursor salt.

“By choosing the right precursor, we can ensure that all the reduction we measure is on the surface and not in the solution,” he explained. “That allowed us to make meaningful measurements about the growth, which is controlled by the type of facet, as well as presence of a twin boundary, corresponding to distinctive growth patterns and end results.”

Over the course of nearly a year, visiting graduate research assistant Tung-Han Yang studied the nanocrystal growth using different types of seeds. Rather than allowing nanocrystal growth from self-nucleation, Xia’s team chose to study growth from seeds so they could control the initial conditions.

Controlling the shape of the nanocrystals is critical to applications in catalysis, photonics, electronics and medicine. Because these noble metals are expensive, minimizing the amount of material needed for catalytic applications helps control costs. 

“When you do catalysis with these materials, you want to make sure the nanocrystals are as small as possible and that all of the atoms are exposed to the surface,” said Xia. “If they are not on the surface, they won’t contribute to the activity and therefore will be wasted.”

The ultimate goal of the research is a database that scientists can use to guide the growth of nanocrystals with specific sizes, shapes and catalytic activity. Beyond palladium, the researchers plan to publish the results of kinetic studies for gold, silver, platinum, rhodium and other nanocrystals. While the pattern of energy barriers will likely be different for each, there will be similarities in how the energy barriers control growth, Xia said.

“It’s really how the atoms are arranged on the surface that determines the surface energy,” he explained. “Depending on the metals involved, the exact numbers will be different, but the ratios between the facet types should be more or less the same.”

Xia hopes that the work of his research team will lead to a better understanding of how the autocatalytic process works in the synthesis of these nanomaterials, and ultimately to broader applications.

“If you want to control the morphology and properties, you need this information so you can choose the right precursor and reducing agent,” said Xia. “This systematic study will lead to a database on these materials. This is just the beginning of what we plan to do.”

In addition to the researchers already mentioned, the study also included Shan Zhou, Kyle Gilroy, Legna Figueroa-Cosme, Yi-Hsien Lee and Jenn-Ming Wu.

This work was supported in part by a research grant from the NSF (CHE 1505441) and startup funds from the Georgia Institute of Technology. The electron microscopy studies were performed at Georgia Tech’s Institute for Electronics and Nanotechnology, a member of the National Nanotechnology Coordinated Infrastructure supported by the NSF (ECCS-1542174).

CITATION: Tung-Han Yang, et al., “Autocatalytic surface reduction and its role in controlling seed-mediated growth of colloidal metal nanocrystals,” (Proceedings of the National Academy of Sciences, 2017). http://dx.doi.org/10.1073/pnas.1713907114

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Media Relations Contact: John Toon (jtoon@gatech.edu) (404-894-6986).

Writer: John Toon

By statistically analyzing clues intercepted through espionage, computer science pioneers in the 1940s were able to work out the rules of the Enigma code, turning a string of gibberish characters into plain language to expose German war communications. And today, a team that included computational neuroscientist Eva Dyer, who recently joined the Georgia Institute of Technology, used cryptographic techniques inspired by Enigma’s decrypting to predict, from brain data alone, which direction subjects will move their arms.

The work by researchers from the University of Pennsylvania, Georgia Tech, and Northwestern University could eventually help decode the neural activity underpinning more complex muscle movements and become useful in prosthetics, or even speech, to aid patients with paralysis.

During the war, the team that cracked Enigma, led by Alan Turing, considered the forebear of modern computer science, analyzed the statistical prevalence of certain letters of the alphabet to understand how they were distributed in messages like points on a map. That allowed the code breakers to eventually decipher whole words reliably.

In a similar manner, the neurological research team has now mapped the statistical distribution of more prevalent and less prevalent activities in populations of motor neurons to arrive at the specific hand movements driven by that neural activity.

The research team was led by University of Pennsylvania professor Konrad Kording, and Eva Dyer, formerly a postdoctoral researcher in Kording’s lab and now an assistant professor at Georgia Tech. They collaborated with the group of Lee Miller, a professor at Northwestern University. They published their study on December 12, 2017, in the journal Nature Biomedical Engineering.

Neuron firing pattern

In an experiment conducted in animal models, the researchers took data from more than one hundred neurons associated with arm movement. As the animals reached for a target that appeared at different locations around a central starting point, sensors recorded spikes of neural activity that corresponded with the movement of the subject’s arm.

“Just looking at the raw neural activity on a visual level tells you basically nothing about the movements it corresponds to, so you have to decode it to make the connection,” Dyer said. “We did it by mapping neural patterns to actual arm movements using machine learning techniques inspired by cryptography.”

The statistical prevalence of certain neurons’ firings paired up reliably and repeatedly with actual movements the way that, in the Enigma project, the prevalence of certain code symbols paired up with the frequency of use of specific letters of the alphabet in written language. In the neurological experiment, an algorithm translated the statistical patterns into visual graphic patterns, and eventually, these aligned with the physical hand movements that they aimed to decode.

“The algorithm tries every possible decoder until we get something where the output looks like typical movements,” Kording said. “There are issues scaling this up — it’s a hard computer science problem — but this is a proof-of-concept that cryptanalysis can work in the context of neural activity.

“At this point, the cryptanalysis approach is very new and needs refining, but fundamentally, it’s a good match for this kind of brain decoding,” Dyer said.

Brain decoding does face a fundamental challenge that code-breaking doesn't.

In cryptography, code-breakers have both the encrypted and unencrypted messages, so all they need to do is to figure out which rules turn one into the other. "What we wanted to do in this experiment was to be able to decode the brain from the encrypted message alone,” Kording said.

Hear PODCAST: The Brain, Cosmos in the Cranium, Part II -- neurons' secrets and how they make the brain compute

Brain-computer interfaces

A cryptanalysis approach to decoding neural activity is particularly attractive when it comes to brain-computer interfaces that control prosthetics.

Existing brain-computer interfaces can already use such data to move a robotic prosthesis, but Kording and Dyer’s experiment has achieved a significant innovation. Existing technology uses a process known as supervised learning, in which the interface can be trained to recognize which neural firings correspond to which intended physical movements, and can thus “replay” those movements when the subject's motor neurons produce a pattern the device has been trained to recognize.

The new research could do away with the training period required for existing brain-computer interfaces to function and allow robotic limbs to directly interpret their user’s thoughts without even having to be calibrated. It would represent a significant quality-of-life improvement for patients wearing them.

“Supervised training may sound simple, but actually, it can be long and troublesome, and in the end, it can even fail,” Dyer said. “For example, if the patient’s arm is not paralyzed but instead is missing, it’s really hard for the training to work.”

The researchers’ innovation could mean the difference between a patient straining to mentally picture how the arm should move with possibly cumbersome results, and willfully moving the arm in a virtually natural way.

Doorway to mindreading  

This cryptanalysis approach also offers promise for brain-computer interfaces to achieve literal mind-reading, the way decoding Enigma allowed for reading encrypted texts.

A patient repeatedly thinking the same sentences would generate neural patterns. “We could build a decoder that transforms those patterns until they look like language,” Kording said. “I think we should be able to do this within the next decade.”

A consistent improvement in brain recording technology could help put this goal within reach. This could become useful for patients unable to speak but could also possibly be abused in espionage, Kording warned. But there's still time to work out the direction future applications take on.

An evolutionary stroke of luck has made this cryptanalysis approach possible. “The brain ended up with this encryption system through natural selection,” Kording said. “So, it’s essentially making the same kind of ‘mistakes’ that allowed us to crack Enigma in the first place.”    

Modern encryption systems are so refined they’re impossible to crack. Enigma, on the other hand, was new enough during World War II that it had small imperfections that gave decrypters a pathway into its secrets, making its cracking a fitting inspiration for brain decoding.

PODCAST: The Brain, Cosmos in the Cranium, Part I - when the brain's fate hangs by a few molecules

PODCAST: The Brain, Part III - how we get around, how we focus, and how we zone out

Researchers Mohammad Gheshlaghi Azar, Hugo L Fernandes, Matthew Peich, Stephanie Naufel and Lee Miller of Northwestern University coauthored the study. The work was supported by the National Institute of Neurological Disorders and Stroke through grants R01 NS053603 and R01 NS074044. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsor.

While the specific mechanism by which the nanotextured material kills bacteria requires further study, the researchers believe tiny spikes and other nano-protrusions created on the surface puncture bacterial membranes to kill the bugs. The surface structures don’t appear to have a similar effect on mammalian cells, which are an order of magnitude larger than the bacteria.

Beyond the anti-bacterial effects, the nano-texturing also appears to improve corrosion resistance. The research was reported December 12 in the journal ACS Biomaterials Science & Engineering by researchers at the Georgia Institute of Technology. 

“This surface treatment has potentially broad-ranging implications because stainless steel is so widely used and so many of the applications could benefit,” said Julie Champion, an associate professor in Georgia Tech’s School of Chemical and Biomolecular Engineering. “A lot of the antimicrobial approaches currently being used add some sort of surface film, which can wear off. Because we are actually modifying the steel itself, that should be a permanent change to the material.”

Champion and her Georgia Tech collaborators found that the surface modification killed both Gram negative and Gram positive bacteria, testing it on Escherichia coli and Staphylococcus aureus. But the modification did not appear to be toxic to mouse cells – an important issue because cells must adhere to medical implants as part of their incorporation into the body.

The research began with a goal of creating a super-hydrophobic surface on the stainless steel in an effort to repel liquids – and with them, bacteria. But it soon became clear that creating such a surface would require the use of a chemical coating, which the researchers didn’t want to do. Postdoctoral Fellows Yeongseon Jang and Won Tae Choi then proposed an alternative idea of using a nanotextured surface on stainless steel to control bacterial adhesion, and they initiated a collaboration to demonstrate this effect.

The research team experimented with varying levels of voltage and current flow in a standard electrochemical process. Typically, electrochemical processes are used to polish stainless steel, but Champion and collaborator Dennis Hess – a professor and Thomas C. DeLoach, Jr. Chair in the School of Chemical and Biomolecular Engineering – used the technique to roughen the surface at the nanometer scale.

“Under the right conditions, you can create a nanotexture on the grain surface structure,” Hess explained. “This texturing process increases the surface segregation of chromium and molybdenum and thus enhances corrosion resistance, which is what differentiates stainless steel from conventional steel.”

Microscopic examination showed protrusions 20 to 25 nanometers above the surface. “It’s like a mountain range with both sharp peaks and valleys,” said Champion. “We think the bacteria-killing effect is related to the size scale of these features, allowing them to interact with the membranes of the bacterial cells.”

The researchers were surprised that the treated surface killed bacteria. And because the process appears to rely on a biophysical rather than chemical process, the bugs shouldn’t be able to develop resistance to it, she added.

A second major potential application for the surface modification technique is food processing equipment. There, the surface treatment should prevent bacteria from adhering, enhancing existing sterilization techniques. 

The researchers used samples of a common stainless alloy known as 316L, treating the surface with an electrochemical process in which current was applied to the metal surfaces while they were submerged in a nitric acid etching solution.

Application of the current moves electrons from the metal surface into the electrolyte, altering the surface texture and concentrating the chromium and molybdenum content. The specific voltages and current densities control the type of surface features produced and their size scale, said Hess, who worked with Choi – then a Ph.D. student – and Associate Professor Victor Breedveld in the School of Chemical and Biomolecular Engineering, and Professor Preet Singh in the School of Materials Science and Engineering, to design the nanotexturing process.

To more fully assess the antibacterial effects, Jang engaged the expertise of Andrés García, a Regents’ Professor in Georgia Tech’s Woodruff School of Mechanical Engineering, and Graduate Student Christopher Johnson. In their experiments, they allowed bacterial samples to grow on treated and untreated stainless steel samples for periods of up to 48 hours.

At the end of that time, the treated metal had significantly fewer bacteria on it. That observation was confirmed by removing the bacteria into a solution, then placing the solution onto agar plates. The plates receiving solution from the untreated stainless steel showed much larger bacterial growth. Additional testing confirmed that many of the bacteria on the treated surfaces were dead.

Mouse fibroblast cells, however, did not seem to be bothered by the surface. “The mammalian cells seemed to be quite healthy,” said Champion. “Their ability to proliferate and cover the entire surface of the sample suggested they were fine with the surface modification.”

For the future, the researchers plan to conduct long-term studies to make sure the mammalian cells remain healthy. The researchers also want to determine how well their nanotexturing holds up when subjected to wear. 

“In principle, this is very scalable,” said Hess. “Electrochemistry is routinely applied commercially to process materials at a large scale.”

CITATION: Yeongseon Jang, et al., “Inhibition of Bacterial Adhesion on Nano-Textured Stainless Steel 316L by Electrochemical Etching,” (ACS Biomaterials Science & Engineering, 2017). http://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.7b00544

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But now a new study reveals, in fine detail, things that make these special bristles collapse -- and also recover. The research increases understanding of these chemical brushes that have many potential uses.

What are polyelectrolyte brushes?

Polyelectrolyte brushes look a bit like soft bushes, such as shoeshine brushes, but they are on the scale of large molecules and the “bristles” are made of polymer chains. Polyelectrolyte brushes have a backing, or substrate, and the polymer chains tethered to the backing like soft bristles have chemical properties that make the brush potentially interesting for many practical uses.

But polymers are stringy and tend to get tangled or clumped, and keeping them straightened out, like soft bristles, is vital to the function of these micron brushes. Researchers at the Georgia Institute of Technology, the University of Chicago, and the Argonne National Laboratory devised experiments that caused polyelectrolyte brush bristles to collapse and then recover from the collapse.

They imaged the processes in detail with highly sensitive atomic force microscopy, and they constructed simulations that closely matched their observations. Principal investigator Blair Brettmann from Georgia Tech and the study’s first authors Jing Yu and Nicholas Jackson from the University of Chicago published their results on December 8, 2017, in the journal Science Advances.

Their research was supported by the U.S. Department of Energy, the National Science Foundation, and the Argonne National Laboratory.

From faux DNA to lubricants

The potential future payoff for the researchers’ work spans industrial materials to medicine.

For example, polyelectrolyte brushes make for surfaces that have their own built-in lubrication. “If you attach the brushes to opposing surfaces, and the bristles rub against each other, then they have really low friction and excellent lubrication properties,” said Blair Brettmann, who led the study and recently joined Georgia Tech from the University of Chicago.

Polyelectrolyte brushes could also one day find medical applications. Their bristles have been shown to simulate DNA and encode simple proteins. Other brushes could be engineered to repel bacteria from surfaces. Some polyelectrolyte brushes already exist in the body on the surface of some cells.

Polyelectrolyte brushes can do so many different things because they can be engineered in so many variations.

“When you build the brushes, you have a lot of control,” said Brettmann, who is an assistant professor in Georgia Tech’s School of Materials Science and Engineering. “You can control on the nanoscale how far apart the polymer chains (the bristles) are spaced on the substrate and how long they are.”

They’re intricate and sensitive

For all their great potential, polyelectrolyte brushes are also complex and sensitive, and a lot of research is needed to understand how to optimize them.

The polymer chains have positive and negative ionic, or electrolytic, charges alternating along their lengths, thus the name “polyelectrolyte.” Chemists can string the polymers together using various chemical building blocks, or monomers, and design nuanced charge patterns up and down the chain.

There’s more complexity: Backing and bristles are not all that make up polyelectrolyte brushes. They’re bathed in solutions containing gentle electrolytes, which create a balanced ionic pull from all sides that props the bristles up instead of letting them collapse or entangle.

“Often these mixtures have a bunch of other stuff in them, so the complexity of this makes it really hard to understand fundamentally,” Brettmann said, “and thus hard to be able to predict behavior in real applications.”

Invading impurities

When other chemicals enter into these well-balanced systems that make up polyelectrolyte brushes, they can make the bristles collapse. For example, the addition of very powerful electrolytes can act like a flock of wrecking balls.

In their experiment, Brettmann and her colleagues used a powerful ionic compound built around yttrium, a rare earth metal with a strong charge. (The ion was trivalent, or had a valence of 3.) The ionic forces from just a low dose of the yttrium electrolyte made the polymer bristles curl up like clumps of sticky spaghetti.

Then the researchers increased the concentration of the gentler ions, which restored support, propping the bristles back up. Atomic force microscope imaging revealed highly regular patterns of collapse and re-extension.

These patterns were reflected well in the simulations; the reliability of the effects of the ions on collapse and recovery even more so. The ability to build such an accurate simulation reflects the strong consistency of the chemistry, which is good news for potential future research and practical applications.

Useless becomes useful

For all the dysfunction that bristle collapses can cause, the ability to collapse them on purpose can be useful. “If you could collapse and reactivate the bristles systematically, you could adjust the degree of lubrication, for example, or turn lubrication on and off,” Brettmann said.

The brushes also could regulate chemical reactions involving micro- and nanoparticles by extending and collapsing the bristles.

“Coatings and films are often made by carefully combining engineered particles, and you can use these brushes to keep these particles suspended and separate until you’re ready to let them meet, bond, and form the product,” Brettmann said.

When the polyelectrolyte brush’s bristles are extended, they act as a barrier to hold the particles apart. Collapse the bristles out of the way on purpose, and the particles can come together.

It’s a nasty world

The experiments were performed with very clean, robust, and uniform compounds unlike the jumble of chemicals that can exist in natural or even industrial systems.

“The bristles we used were polystyrene sulfonate, which is a very strong polyelectrolyte, not sensitive to pH or much else,” Brettmann said. “Biopolymers like polysaccharides, for example, are a lot more sensitive.”

Like many experiments, this one was a departure from real-world conditions. But by creating a foundation for understanding how these systems work, Brettmann wants eventually to be able to move on to sensitive scenarios to realize more of polyelectrolyte brushes’ practical potential.

Also READ: Paper-based supercapacitor 

The study was co-authored by Xin Xu, Marina Ruths, Juan de Pablo and Matthew Tirrell. The research was funded by the U.S. Department of Energy Office of Science, Program in Basic Energy Sciences, Materials Sciences and Engineering Division, the National Science Foundation’s Division of Civil, Mechanical, and Manufacturing Innovation (grants 1562876 and 1161475), the Argonne National Laboratory Maria Goeppert Mayer Named AQ41Fellowship. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of those sponsors.

The first amputee to use it, a musician who lost part of his right arm five years ago, is now able to play the piano for the first time since his accident. He can even strum the Star Wars theme song.

“Our prosthetic arm is powered by ultrasound signals,” said Gil Weinberg, the Georgia Tech College of Design professor who leads the project. “By using this new technology, the arm can detect which fingers an amputee wants to move, even if they don’t have fingers.”

Jason Barnes is the amputee working with Weinberg. The 28-year-old was electrocuted during a work accident in 2012, forcing doctors to amputate his right arm just below the elbow. Barnes no longer has his hand and most of his forearm but does have the muscles in his residual limb that control his fingers.

Barnes’ everyday prosthesis is similar to the majority of devices on the market. It’s controlled by electromyogram (EMG) sensors attached to his muscles. He switches the arm into various modes by pressing buttons on the arm. Each mode has two programmed moves, which are controlled by him either flexing or contracting his forearm muscles. For example, flexing allows his index finger and thumb to clamp together; contracting closes his fist.

“EMG sensors aren’t very accurate,” said Weinberg, director of Georgia Tech’s Center for Music Technology. “They can detect a muscle movement, but the signal is too noisy to infer which finger the person wants to move. We tried to improve the pattern detection from EMG for Jason but couldn’t get finger-by-finger control.”

But then the team looked around the lab and saw an ultrasound machine. They partnered with two other Georgia Tech professors – Minoru Shinohara, Chris Fink (College of Sciences) and Levent Degertekin (Woodruff School of Mechanical Engineering) — and attached an ultrasound probe to the arm. The same kind of probe doctors use to see babies in the womb could watch how Barnes’ muscles moved.

“That’s when we had a eureka moment,” said Weinberg.

When Barnes tries to move his amputated ring finger, the muscle movements differ from those seen when he tries to move any other digit. Weinberg and the team fed each unique movement into an algorithm that can quickly determine which finger Barnes wants to move. The ultrasound signals and machine learning can detect continuous and simultaneous movements of each finger, as well as how much force he intends to use.

“It’s completely mind-blowing,” said Barnes. “This new arm allows me to do whatever grip I want, on the fly, without changing modes or pressing a button. I never thought we’d be able to do this.”

This is the second device Weinberg’s lab has built for Barnes. His first love is the drums, so the team fitted him with a prosthetic arm with two drumsticks in 2014. He controlled one of the sticks. The other moved on its own by listening to the music in the room and improvising.

The device gave him the chance to drum again. The robotic stick could play faster than any drummer in the world. Worldwide attention has sent Barnes and Weinberg’s robots around the globe for concerts across four continents. They’ve also played at the Kennedy Center in Washington, D.C. and Moogfest.

That success pushed Weinberg to take the next step and create something that gives Barnes the dexterity he’s lacked since 2012.

“If this type of arm can work on music, something as subtle and expressive as playing the piano, this technology can also be used for many other types of fine motor activities such as bathing, grooming and feeding,” said Weinberg. “I also envision able-bodied persons being able to remotely control robotic arms and hands by simply moving their fingers.”

Emily’s leukemia is still in remission five years after undergoing a 2012 clinical trial at Children’s Hospital of Philadelphia of the groundbreaking drug by Novartis, Kymriah (tisagenlecleuce). In a global trial, 83 percent of terminally-ill patients went into complete remission. In August of this year, Emily and her family celebrated the U.S. Food and Drug Administration’s (FDA) approval of the revolutionary T-cell therapy for acute lymphocytic leukemia, the world’s first genetically engineered immune therapy.

It’s the kind of epic story that reminds Roy, a researcher at the Petit Institute for Bioengineering and Bioscience at the Georgia Institution of Technology, why he does what he does.

“These patients, like Emily, are incredibly brave,” says Roy, who holds the Robert Milton Chair in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “They face the unknown – these potentially risky, potentially promising therapies. At the end of the day, it is for them, for the patients. I think everybody who works in the cellular therapies space, works with that motivation in mind.”

Over the past few years, Roy has taken the lead role in expanding that space at Georgia Tech, where he is director of the Center for ImmunoEngineering, the Marcus Center for Cell-Therapy Characterization and Manufacturing (MC3M), and the recently-established National Science Foundation Engineering Research Center for Cell Manufacturing Technologies (CMaT).

Roy is running point in a widespread endeavor at Georgia Tech to develop cutting-edge cell therapies, and CMaT, which launched this fall, is the latest highlight in a surge of cell therapy-related activity that goes back to the early 1990s, “when we went after a Whitaker Foundation development award and decided the focus should be on tissue engineering – the engineering of replacement tissues using living cells,” notes Bob Nerem, founding director of the Petit Institute.

“We got that award and began our initiative with three initial focus areas,” Nerem adds. “The cardiovascular area, diabetes, and orthopaedic tissue engineering.  Later, we added the neural area, which in many ways has to be considered the holy grail, because there aren’t any viable treatments for many neural issues.”

And that’s the point of cell therapies: they offer a powerful alternative to patients with a dwindling supply of hope.

“We believe cell-based therapies can provide new treatment options," Nerem says. "We feel that’s the future, and we hope to make a major contribution for patients who are running out of options."

Collaborative Heft

In September 2017, the National Science Foundation (NSF) announced it was awarding $20 million to a Georgia Tech-led consortium of universities to establish CMaT, which will serve as the catalyst for a new epoch in the evolution of cell therapies. CMaT researchers will collaborate with industry and clinical partners to develop tools and technologies for the consistent, scalable, and affordable production of living therapeutic cells, which could be used to battle cancer, heart disease, autoimmune diseases, and other disorders.

Almost 20 years earlier, NSF sparked cell therapy research with a $12.5 award to establish GTEC – the Georgia Tech/Emory Center for the Engineering of Living Tissues.

“Georgia Tech has been showing great leadership in cell therapy research for a number of years,” says Bob Guldberg, executive director of the Petit Institute and professor in the Woodruff School of Mechanical Engineering. “GTEC really helped build a critical mass of people here doing regenerative medicine research and established Georgia Tech as a national leader in tissue engineering and regenerative medicine.”

GTEC has since evolved into the Regenerative Engineering and Medicine (REM) research center, a collaboration of Tech, Emory University, and the University of Georgia (UGA).

With CMaT, the number of collaborators has grown. In addition to Georgia Tech, major partners include UGA, the University of Wisconsin-Madison, and the University of Puerto Rico (Mayaguez campus), as well as affiliate partners Emory, the Gladstone Institutes, Michigan Technological University, and the University of Pennsylvania.

A collaboration across many disciplines is going to be necessary to tackle the complex challenge of properly manufacturing cell therapies. Georgia Tech seems well-poised to lead such an effort, because of its own multidisciplinary capacity.

“Now we need a broad group of stakeholders to come into play, not only the clinicians and the biomedical and chemical engineers that have traditionally dominated the field,” says Roy, who led the National Cell Manufacturing Consortium – a collaboration of more than 25 companies and 15 academic institutions, along with government agencies and private foundations, that produced a national roadmap for large-scale cell therapy manufacturing.

“We’re bringing in electrical engineers, mechanical engineers, industrial engineers, basic scientists, as well as automation and robotics personnel and experts, data scientists, computational scientists,” Roy adds. “Bring all of that together with policy experts and our natural science programs, and it makes an ideal coalition. That crosstalk between so many disciplines at Georgia Tech makes it an ideal place for an effort like CMaT.”

Tech Marks the Spot

In the spring of 2014, the National Institute of Standards and Technology (NIST) awarded a $500,000 advanced technology planning grant to Georgia Tech, funds specifically allotted for creating a national roadmap and consortium targeting cell manufacturing. The NCMC emerged from that, under the direction of Georgia Tech and the Georgia Research Alliance (GRA).

In June 2016 at the White House Organ Summit, the consortium presented its 10-year plan, Technology Roadmap 2025, that basically details the critical stages in the manufacturing pipeline, including cell processing, cell preservation, distribution and handling, quality control, standardization, and workforce development.

Six months before the roadmap’s public unveiling, Georgia Tech was already on the right path. In January 2016, The Marcus Foundation awarded Tech $15.7 million to build a new research center for the development of processes and techniques to ensure the consistent, low-cost, large-scale manufacture of high-quality cells to be used in cell therapies. With additional funding from the GRA and Tech, the $23 million MC3M – the first research facility of its kind – was launched.

“The Marcus Center is already serving as a cell characterization hub for a network of clinical trials around the country,” says Guldberg. “This is a tremendously exciting role, because Georgia Tech will have a lot of the data that will be used to correlate what the important attributes of a cell are that determine whether it’s going to work clinically.”

Initial funding for the MC3M was slated for five years, after which time the center would be expected to support itself with corporate, government, and nonprofit funding. So, through MC3M, Georgia Tech (in partnership with institutions around the state and country) applied for federal funding from NSF to further augment its research and development in cell manufacturing.

With a strategic roadmapping plan in place and funding for a unique cell manufacturing and characterization center secured, Georgia Tech was well positioned to apply for one of the highly competitive NSF Engineering Research Centers. From an initial group of more than 170 proposals nationwide, CMaT was selected as one of just four newly funded centers for 2017.  CMaT is headquartered in the Petit Institute for Bioengineering and Bioscience and will focus on developing enabling technologies as well as the workforce needed by the emerging cell manufacturing industry.   

“I think we’re at a critical juncture in cell manufacturing,” says Johnna Temenoff, Petit Institute researcher, professor in the Coulter Department, and deputy director of CMaT.

“If we do this right, there’s a huge potential,” adds Temenoff, co-director of REM. “The long term goal is to have a large pool of high-quality cells that we can get to people around the world in developed and developing countries.”

This idea of creating affordable new-age medicine for a global population is a major goal for cell therapy and manufacturing researchers like Roy, who notes the high cost of cell therapies. The pioneering Novartis T-cell therapy that cured Emily Whitehead’s cancer is listed at $475,000.

“These treatments can be very expensive, and inaccessible to a majority of the people in the world,” Roy says. “So, the burning question is, how do we bring this to scale and make these therapies cost-effective and available for a broad population across the world, regardless of socioeconomic status? As long as we can develop reproducible product at a much lower cost and achieve manufacturing that is tightly controlled and delivers consistent high-quality cells, we’re going to get the answer.”

Homegrown Meds

Cell therapies can come from a couple of different sources. The two most common types of stem cell transplants for cell therapies are autologous and allogeneic. With an autologous transplant, the patient’s own cells are removed, expanded, modified for a therapeutic purpose – finding and attacking cancer, for example. In an allogeneic transplant, the patient receives cells – say, bone marrow or peripheral blood stem cells – from a matching donor, typically a sibling.

“Cells can do many things that a single molecule can’t do,” Roy says. “A cell is a complex entity – a living and breathing entity. They can multiply inside the body, attack and kill certain other cells, like cancer, change the behavior of other cells, like immune cells. These can be extremely powerful drugs. If not harnessed properly, they can be deleterious to a patient as well.”

The side effects with the Novartis drug almost killed Emily Whitehead. These include high fevers, low blood pressure, seizures, liver abnormalities, and heart irregularities. The company and clinicians have developed strategies to manage and minimize the risks.

In the end, for the great majority of patients in the study, the reward was well worth the risks. “Our daughter was going to die, and now she leads a normal life,” Emily’s father, Tom Whitehead, told the FDA panel that endorsed the therapy.

Wilbur Lam is a physician – a hemotologist/oncologist – as well as a researcher in the Petit Institute. He’s seen what happens when standard therapies fail and much prefers having an alternative.

“Cell therapies are the next generation of therapeutics. They offer hope,” says Lam, associate professor in the Coulter Department, and a pediatrician with Children’s Healthcare of Atlanta and the Emory School of Medicine.

His lab has developed a technology in which the patient’s own platelets – the cells that control blood clotting – can be used as a delivery system for drugs. “When it gets to a bleed, it can release its cargo, because the platelet is fine tuned to react to the environment,” Lam says.

It’s a treatment that can be used for patients with hemophilia, or patients who have experienced trauma and are bleeding. “We can also fine tune this system to go in the opposite direction, use it to deliver anti-clotting medications for patients who have heart attacks or strokes,” Lam says. “All of which is enabled by the patient’s own platelets, which act as the brain and muscle, releasing the drug only where it needs to be.”

Petit Institute researcher Melissa Kemp has some personal reasons for her interest and work in cell therapy research, which is based in computational systems biology. Her lab is interested in how intracellular and extracellular environments control the transmission of cellular information, studying living systems using engineering and computational tools, basically looking at complex protein networks the way an electrical engineer might look at a power grid.

“We want to understand how these things are connected together – if you have a failure at one spot, how does that propagate and cause a blackout in another location,” says Kemp, associate professor in the Coulter Department, whose family medical history includes conditions that cell therapies would address.

“Some of the target applications that Georgia Tech researchers have in mind include cardiovascular disease, osteoarthritis, cancer – all of which run in my family,” says Kemp, whose father is a cancer survivor. “So, I’m really excited about the potential of these end applications. The exciting aspect about cellular manufacturing is the ability to really revolutionize medicine in this century.”

Watch the Video

Baratunde Cola, Mary Frank Fox, and Joshua Weitz, who are members of AAAS, were elected by their peers to receive the honor and join hundreds of their contemporaries who became fellows this year. “This year 396 members have been awarded this honor by AAAS because of their scientifically or socially distinguished efforts to advance science or its applications,” the AAAS wrote in its announcement of this year’s fellows.

All three Georgia Tech fellows saw the AAAS Fellowship as encouragement to continue serving science and humanity.

The three have excelled in research in the following fields, according to AAAS: Cola in nanoscale engineering, Fox in the participation and performance of women and men in science, and Weitz in virus dynamics in populations and in ecosystems. Here are summaries of the researchers’ achievements and interests.

Baratunda Cola may be best known for engineering the first-ever optical rectenna. A rectenna, or rectifying antenna, turns electromagnetic waves into direct current electricity, and Cola’s invention was the first known to work with sunlight instead of radio waves, making it an innovation in efficient solar energy generation.

Cola, who is an associate professor in The George W. Woodruff School of Mechanical Engineering at Georgia Tech, is currently focused on the transfer of heat, and the conversion of energy in nanostructures, particularly those based on carbon nanotubes. He holds three carbon nanotube related patents and is interested in making his innovations producible on a large scale for practical use.

“I was honored that AAAS chose to recognize my contributions to science over the years,” Cola said. “The fellowship gives a bigger platform to my work so it can reach more people and be useful to them.”

Cola’s vision transcends arbitrary confines of a research field. “I think of myself less as being a mechanical engineer and more as a person concerned with the advancement and well-being of people, and I appreciate the power of science to positively affect lives through practical applications.”

In April, Cola received the highest honor awarded by the National Science Foundation to up-and-coming scientists and engineers. Like the AAAS Fellowship, the Alan T. Waterman award also recognized Cola’s achievements in transforming light and heat into electricity on the nanoscale, and it added $1 million in funding to his research.

Cola also serves as CEO of Carbice Corporation, a Georgia Tech spinoff company that has developed a heat-conducting tape that helps prevent electronic devices from overheating.

Mary Frank Fox is known for her research on women and men in scientific organizations and occupations. She is nationally recognized as a leader on issues of diversity, equity, and equity in science, and her work has had a significant influence on science and technology policy.

Fox, who is an ADVANCE Professor at the School of Public Policy in Georgia Tech’s Ivan Allen College of Liberal Arts, is particularly interested in how social and organizational settings, in which scientists are educated and work, influence their performance. She holds multiple board of director positions in societies connected to science and technology policy.

“I’m deeply honored by the AAAS award,” Fox said. “I value that it recognizes my years of research on women and men in sciences and the policy implications for equity.”

Fox sees the award as recognition that her work advances science and is aligned with AAAS’s commitments. “I’m one of the founders of this area of science, and I value this award recognizing this research that advances science,” Fox said.

Joshua Weitz uses models to predict the effects of viruses on populations and on ecosystems, but his work encompasses many complex biological systems. His group combines methods from physics, math, computational biology, and bioinformatics to develop in-depth analytical models of biological dynamics to understand experimental and environmental data.

In the field of virology, he applies this approach to the molecular workings of viruses, their spread through a population and their evolution into new strains. His work is theoretical, but he uses his detailed computational methods to collaborate with experimentalists. Weitz is a professor in Georgia Tech’s School of Biological Sciences, Courtesy Professor of Physics and the Director of the Interdisciplinary Graduate Program in Quantitative Biosciences.

“When AAAS first informed me, I was honored and humbled.  And I was proud of my group and its collective effort in the last 10 years at Georgia Tech to study viral ecology,” Weitz said.

“The mission of the AAAS is ever more important in these times, and being a fellow gives us a greater responsibility to communicate our research beyond the scientific community, to let the public know how it serves society’s betterment by improving public health and environmental health.”

The American Association for the Advancement of Science lays claim to the distinction of being “the world’s largest general scientific society.” AAAS was founded in 1848 and publishes the journal Science as well as many other prestigious research periodicals. The AAAS Fellowship began in 1874.

In a new study, physicists and evolutionary biologists at the Georgia Institute of Technology have shown how physical stress may have significantly advanced the evolutionary path from single-cell to multicellular organisms. In experiments with clusters of yeast cells called snowflake yeast, forces in the clusters’ physical structures pushed the snowflakes to evolve.

“The evolution of multicellularity is as much a matter of physics as it is biology,” said biologist Will Ratcliff, an assistant professor in Georgia Tech’s School of Biological Sciences.

The bigger they are…

Like the first ancestors of multicellular organisms, in this study the snowflake yeast found itself in a conundrum: As it got bigger, physical stresses tore it into smaller pieces. So, how to sustain the growth needed to evolve into a complex multicellular organism?

In the lab, those shear forces played right into evolution’s hands, laying down a track to direct yeast evolution toward bigger, tougher snowflakes.

“In just eight weeks, the snowflake yeast evolved larger, more robust bodies by figuring out soft matter physics that took humans hundreds of years to learn,” said Peter Yunker, an assistant professor in Georgia Tech’s School of Physics. He and Ratcliff collaborated on the research that documented the evolution and measured the physical properties of mutated snowflake yeast.

They published their results on November 27, 2017, in the journal Nature Physics. The work was funded by the NASA Exobiology program, the National Science Foundation, and a Packard Foundation Fellowship to Ratcliff.

Questions and answers

Here are some questions and answers to illuminate the study and its significance.

But first, some background: Baker’s yeast, which was used in these experiments, is usually a single-cell organism. Yeast cells with a well-known mutation stick together in groups called snowflakes.

That was not the focus of the experiments, but the yeast snowflakes were the starting point in this study on the evolution of multicellularity.

Why is this study significant?

Such a cell cluster like a yeast snowflake is not a well-integrated multicellular organism yet. To make it to even simple multicellularity like that of some algae is a very long evolutionary haul.

“It’s a journey of a thousand steps,” Ratcliff said. “The key change is for this group of cells not to evolve as a gang of single cells but as one multicellular individual.”

In this work, the researchers showed how snowflake yeast took first steps in that direction by evolving more resilient multicellular bodies that sustained growth. The process was mainly driven by physical forces, as the simple snowflakes did not have complex inner biological workings that were capable of being the main drivers.

“This is an amazing example of multicellular adaptation around physical constraints well before the evolution of a cellular developmental program,” Yunker said.

How does this evolution via physical stress work?

“Yeast snowflakes grew by adding cells end to end to form branches kind of like those of a bush,” Yunker said. “But the branches crowded each other, and the stresses that result made some break off.”

The breakage chopped down the size of individual yeast snowflakes, but after multiple generations, the snowflakes evolved to reduce the crowding of branches by elongating its individual cells.

As a result, the overall snowflakes were less stressed and could grow larger and more robust.

In addition, Georgia Tech researchers discovered that physics made the snowflakes basically have babies. Specifically, the pieces that broke off became propagules that grew into snowflakes of their own.

This reproduction was created by physical force and not by a biological program. Ratcliff published a separate study about the reproduction aspect on October 23, 2017, in the journal Philosophical Transactions of the Royal Society B.

“Physics does a lot for multicellularity,” Ratcliff said. “It also gives it a lifecycle.” Lifecycle refers to birth, growth, reproduction, and death.

“A consensus is forming that for something to really evolve to multicellularity, very early on, a multicellular lifecycle has to develop.”

Also READ: Evolution, What was the Primordial Stew?

How did the experiments select for these specific adaptations?

Ratcliff and Yunker streamlined evolution in the lab by creating a consistent selection regime for the yeast snowflakes to evolve in. In this case, they selected for snowflakes that were best at sinking.

The snowflakes that sank better were heavier, because they grew larger than others in the manner described above, giving them more mass. “The clusters that evolved to grow bigger were therefore also heavier,” Ratcliff said.

This experimental selection setup befitted natural evolution, which also had to select for size to arrive at complex multicellular bodies, which are much, much larger than single cells.

Mutation of branches is genetic. Is physics really so important here?

That’s correct: Random genetic mutations resulted in the better, longer branches in some yeast snowflakes giving them a cumulative weight advantage.

But the propagation of the superior snowflake mutations was the result of physical stresses not breaking the snowflakes until they had grown larger.

The pieces that eventually did break off, due purely to physical force, were the propagules. Some of them carried mutations forward that made the new snowflakes even better at sinking.

And that was a critical step in the multicellular evolution.

How was stress corroborated as the cause of snowflakes splitting apart?

The researchers put the material properties of the snowflakes to the test under an atomic force microscope. “We squished the clusters and measured how much force and energy you needed to break them,” Yunker said.

“The physical measurement indicated closely the size the clusters would attain before they broke off a branch due to stress,” Ratcliff said.

Also READ: 'Cavemen' had better mental health genes?

Coauthors of this study were Shane Jacobeen, Jennifer Pentz, Elyes Graba, and Colin G. Brandys of Georgia Tech. The research was funded by the NASA Exobiology program (grant #NNX15AR33G), the National Science Foundation (grant #IOS-1656549), and a Packard Foundation Fellowship. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of those sponsors.

“We are all so busy,” says Grover, a professor in the School of Chemical and Biomolecular Engineering, a scientific collaborator at the NSF/NASA Center for Chemical Evolution (CCE), and a member of the Center for Space Technology and Research (C-STAR).

Now, Grover, Glass, and others at Tech are members of a growing community that’s coalescing astrobiology activities across campus. In a public debut of sorts, six members of Georgia Tech Astrobiology, as the community calls itself, participated in the 2017 Dragon Con, the premier pop-culture convention on science fiction and fantasy. They wowed the audience, not by fiction or fantasy or over-the-top costumes, but by progress in answering fundamental questions – How did life begin? Where else could life exist? – happening right next door from the meeting venue, at Georgia Tech.

The growing visibility of researchers interested in astrobiology is helping Georgia Tech emerge as a powerhouse in the field. At minimum, says Kenneth Knoespel, a historian of science and professor in the Ivan Allen College of Liberal Arts, “it affirms the importance of this community at Georgia Tech and the importance of astrobiology as a new configuration of disciplines that brings together the natural and human sciences.”  

TEEMING WITH TALENT

“Georgia Tech is clearly recognized as a hub for astrobiology and maybe the one that’s growing the most quickly,” says Edward Goolish, the deputy director of the NASA Astrobiology Institute (NAI), one of the six elements of the NASA Astrobiology Program. People at Georgia Tech, Goolish adds, “have been generous with their time and have contributed in important ways when NASA has reached out to the science community for input.”

The community includes physicists, chemists, biologists, Earth and planetary scientists, and engineers, as well as historians of science and writers. The scientists are figuring out how life emerged and evolved to the biosphere we know, inventing instruments to detect life outside Earth, and searching for other habitable places in the universe. The science historians and writers are witnessing science in the making and perhaps gathering fodder for the next volume of science fiction.

Broadly defined, astrobiology is the study of life in the cosmos. Its central questions are “What is the origin of life?” and “Does life exist beyond Earth?” Humans have asked these questions since time immemorial. That they are still around attests to the difficulty of discovering and assembling the pieces of a formidable puzzle: the emergence of a biosphere on a planet.

How formidable? According to Eric Smith, a theoretician in the NASA Astrobiology Institute’s team at Georgia Tech (NAI-GT), understanding the nature of the transition from a planet without a biosphere to one with a biosphere should be central to origins-of-life inquiries. However, he says, “a lot of the language to enable that understanding doesn’t exist yet.”

THREE PILLARS

At Georgia Tech, research teams are working across the breadth of questions central to astrobiology. Their activities are exemplified by three specialized research groups: CCE, NAI-GT, and C-STAR. 

CCE is building a community in origin-of-life research, said its director, Nicholas V. Hud, at a symposium organized by Georgia Tech Astrobiology last month. In finding answers, CCE takes two approaches, Hud explained. “Bottom up,” it starts with geology and chemistry and understanding the formation of the first polymers of life, which is a major focus of Hud’s. “Top down,” it starts with biology, genetics, and looking back in time at persistent, conserved molecular motifs, as exemplified by the work of Loren Williams on ribosomes.

Like digging a tunnel underground from opposite ends and meeting somewhere in between, the two approaches are converging on the coevolution of the biopolymers of life. Chemistry and biology are telling us the same thing, say Hud and Williams, both professors in the School of Chemistry and Biochemistry (SoCB) and members of the Parker H. Petit Institute for Bioengineering and Bioscience (IBB).

At NAI-GT, “we start at the level of the cell,” says Frank Rosenzweig, the School of Biological Sciences (SoBS) professor who leads the NASA group. “Once you have all this biochemistry wrapped in a cell, what happens then? How do they become associated as multicellular organisms? How do they engage in biochemistries that change the environment? We need to understand the interaction between the evolution of life and the evolution of its abiotic surrounding to have a chance of recognizing life elsewhere.

“Although life on Earth manifests in different forms, all are governed by laws of growth, inheritance, and variability,” says Rosenzweig, also a member of IBB. NAI-GT aims to “illuminate and interpret these laws via laboratory-based evolution experiments with microbial populations.” An example is the exploration of the origin of multicellularity by experimentally evolving yeast, as described in the September symposium by Will Ratcliff, an assistant professor in SoBS.

For C-STAR-affiliated faculty, habitability is one key question. What events and conditions in the abiotic sphere yield environments that support life? The NASA-supported work of Jennifer Glass and Chris Reinhard, in the School of Earth and Atmospheric Sciences (EAS), exemplify the search for answers in this realm.

What signals should we monitor in search of life elsewhere in the universe? What tools do we need to probe for signs of life from the comfort of Earth? What hazards should we prepare for if humans were to go to other worlds?

In EAS, C-STAR members and planetary scientists Carol Paty, Britney Schmidt, and James Wray are co-investigators of NASA-funded projects to answer these questions. So is C-STAR member Paul Steffes, in the School of Electrical and Computer Engineering, as well as C-STAR Director Thomas Orlando and C-STAR member Amanda Stockton, in SoCB.

WHAT’S NEXT

With the talent on campus, Georgia Tech is becoming well known in the field of astrobiology. At the 2017 Astrobiology Scientific Conference, in Mesa, Ariz., last April, the Georgia Tech “posse” numbered about 30 faculty and students. Last summer, attendees of AbGradCon (Astrobiology Graduate Conference) 2017 selected Georgia Tech to host the 2018 event. This popular meeting for students is funded primarily by the NASA Astrobiology Institute.

The astrobiology community at Georgia Tech is “healthy,” Smith says. “The people in strategic positions have good priorities in the sophistication and intellectual integrity they are trying to support.”

The community – now 85 strong and growing – is raring to make its presence felt. It has an ambitious schedule for the 2017-18 school year, spearheaded by the September symposium.

Led by Grover as principal investigator, and with contributions from Glass, Knoespel, Paty, Reinhard, Rosenzweig, Schmidt, Williams, and others – Rebecca Burnett, Ivan Allen College of Liberal Arts; Glenn Lightsey, School of Aerospace Engineering and C-STAR; and Christopher Parsons, CCE – their proposal for seven projects received funding from the Georgia Tech Strategic Plan Advisory Group (SPAG) and the Colleges of Engineering, Liberal Arts, and Sciences.

The projects aim to showcase the quality and variety of astrobiology projects at Tech, highlight the social impact of these projects, and strengthen the sense of community among faculty and students. The goals will be achieved through formal gatherings, educational innovations, and public outreach.

“As I see it, the point of research universities is to tackle the really important, really deep, and really challenging questions – the ones at the edge of, or even beyond, our reach; the ones that present not just the possibility but the likelihood of failure,” said College of Sciences Dean and Sutherland Chair Paul M. Goldbart at the September symposium. “It’s our duty as administrators to do everything we can to support this kind of truly adventurous research.”

What the astrobiology community is doing not only is exciting, Goldbart said. But also, “it could hardly fit better with the dreams of the College of Sciences and of Georgia Tech.” 

Georgia Tech Researchers Working Toward the Goals of NASA’s Astrobiology Program

Planetary Science and Technology Through Analog Research (P-STAR)
               Jennifer Glass, School of Earth and Atmospheric Sciences
               Britney Schmidt, School of Earth and Atmospheric Sciences
               Amanda Stockton, School of Chemistry and Biochemistry

Planetary Instrument Concepts for the Advancement of Solar System Observations (PICASSO)
               Amanda Stockton

Exobiology: Early Evolution of Life and the Biosphere
               Frank Rosenzweig, School of Biological Sciences

Exobiology: Evolution of Advanced Life
               William Ratcliff, School of Biological Sciences

Exobiology: Prebiotic Evolution
               Loren Williams, School of Chemistry and Biochemistry

Exobiology: Methane and Iron Metabolisms in Ancient Oceans 
               Jennifer Glass

School of Earth and Atmospheric Sciences Faculty Affiliated with NASA Astrobiology Institute (NAI)
               Jennifer Glass, Chris Reinhard, and Yuanzhi Tang, with University of California, Riverside, team
               James Wray, with SETI Institute team
              
NAI Team at Georgia Tech School of Biological Sciences
         Kim Chen 
         Phillip Gerrish 
         Matt Herron
         Teresa Jonsson 
         Kennda Lynch
         Frank Rosenzweig 
         William Ratcliff 
         Eric Smith
         Pedram Samani 
         Tim Whelan 

NASA Postdoctoral Program Fellows
          Bradley Burcar, with Nicholas Hud
          Peter Conlin, with William Ratcliff
          Moran Frenkel-Pinter, with Loren Williams
          Kazumi Ozaki, with Chris Reinhard
          Nicholas Speller, with Amanda Stockton

2018 AbGradCon Organizers
               Marcus Bray                    Justin Lawrence
               Bradley Burcar                 Adriana Lozoya
               Anthony Burnetti              Kennda Lynch
               Heather Chilton               Santiago Mestre Fos
               Chase Chivers                 Marshall Seaton
               Dedra Eichstedt               Micah Schaible
               Zachary Duca                  Elizabeth Spiers
               Jennifer Farrar                 Scot Sutton
               Nicholas Kovacs              Nadia Szeinbaum
                                George Tan, Conference Chair 
Note: This list is not meant to be comprehensive; it represents information that was available as of October 2017.

This list was updated on Nov. 21, 2017, to include all members of the NAI Team at Georgia Tech School of Biological Sciences. 

PHOTO CAPTIONS

Georgia Tech at AbSciCon 2017. This photo shows only some of the Georgia Tech researchers who attended. From left: Cesar Menor-Salvan, Nick Hud, Justin Lawrence, Jacob Buffo, Frank Rosenzweig, Amanda Stockton, Britney Schmidt, Kennda Lynch, Gavin Mendez, George Tan, Jennifer Glass, Zachary Duca, Nadia Szeinbaum, Aaron McKee, Chloe Stanton, and Marcus Bray (Courtesy of Jennifer Glass)

Georgia Tech Astrobiology at 2017 Dragon Con. From left: Amanda Stockton, Loren Williams, Kenneth Knoespel, Lisa Yaszek, Chris Reinhard, and Britney Schmidt (Photo by Renay San Miguel)

Organizers and Speakers: “Life in the Cosmos.”
Top, from left: Rebecca Burnett, Carol Paty, Kennda Lynch, Jennifer Glass, Martha Grover, Gongjie Li, and Amanda Stockton
Bottom, from left: Thomas Orlando, Paul Steffes, Frank Rosenzweig, Nicholas Hud, Loren Williams, and William Ratcliff (Photos by Maureen Rouhi)

However, the nematic phase formed by the worms is filled with tiny regions where the local alignment is lost – defects in the otherwise aligned material. In addition, because the worms are constantly moving and changing their configuration, this nematic phase is active and far from equilibrium.

In research reported October 23 in the journal Nature Physics, scientists from the Georgia Institute of Technology and Leiden University in The Netherlands have described the results of a combined theoretical and experimental examination of such an active nematic on the surface of donut-shaped – toroidal – droplets. However, the researchers didn’t use actual worms, but an active nematic composed of flexible filaments covered with microscopic engines that are constantly converting energy into motion.

This particular active material, originally developed at Brandeis University, borrows elements of cellular machinery, with bundles of rod-like microtubules forming the filaments, kinesin motor proteins acting as the engines, and ATP as the fuel. When this activity is combined with defects, the defects come to life, moving around like swimming microorganisms to explore space – in this case, exploring the surface of the toroidal droplets. 

By studying toroidal droplets covered by this active nematic, the researchers confirmed a longstanding theoretical prediction about liquid crystals at equilibrium, first discussed by Bowick, Nelson and Travesset [Phys.Rev. E 69, 041102 (2004)] that nematic defects on the curved surface of such droplets will be sensitive to the local curvature. However, since the active nematic used in this work is far from equilibrium, the researchers also found how the internal activity changed and enriched the expectations.

“There have been predictions that say defects are very sensitive to the space they inhabit, specifically to the curvature of the space,” said Perry Ellis, a graduate student in the Georgia Tech School of Physics and the paper’s first author. “The torus is a great place to investigate this because the outside of the torus, the part that looks locally like a sphere, has positive curvature while the inner part of a torus, the part that looks like a saddle, has negative curvature.” 

“The quantity that characterizes a defect is what we call its topological charge or winding number,” said Alberto Fernandez-Nieves, a professor in Georgia Tech’s School of Physics and another of the paper’s co-authors. “It expresses how the alignment direction of the nematic liquid crystal changes as we go around the defect. This topological charge is quantized, meaning that it can only take values from a discrete set that are multiples of one-half. “

In these experiments, each defect has a topological charge of +1/2 or -1/2. To determine the charge and location of every defect, Ellis observed the toroidal droplets over time using a confocal microscope and then analyzed the resulting video using techniques borrowed from computer vision. The researchers found that even with the molecular motors driving the system out of equilibrium, the defects were still able to sense the curvature, with the +1/2 defects migrating towards the region of positive curvature and the -1/2 defects migrating towards the region of negative curvature. 

In this new work, the scientists took a step forward in understanding how to control and guide defects in an ordered material. 

“We have learned that we can control and guide partially ordered active matter using the curvature of the underlying substrate,” said Fernandez-Nieves. “This work opens opportunities to study how the defects in these materials arrange on surfaces that do not have constant curvature. This opens the door for controlling active matter using curvature.” 

An unexpected finding of the study was that the constant motion of the defects causes the average topological charge to become continuous, no longer taking only values that are multiples of one-half. 

“In the active limit of our experiments, we found that the topological charge becomes a continuous variable that can now take on any value,” said Fernandez-Nieves. “This is reminiscent of what happens to many quantum systems at high temperature, where the quantum, discrete nature of the accessible states and associated variables is lost. Instead of being characterized by quantized properties, the system becomes characterized by continuum properties.”

Ellis’ observations of the droplets compared well with those of numerical simulations done by Assistant Professor Luca Giomi and postdoctoral researcher Daniel Pearce at the Instituut-Lorentz for Theoretical Physics at the Universiteit Leiden in The Netherlands.

“Our theoretical model helped us decipher the experimental results and fully understand the physical mechanism governing defect motion,” said Pearce, “but also allowed us to go beyond the current experimental evidence.” Added Giomi: “Activity changes the nature of the interaction between defects and curvature. In weakly active systems, defects are attracted by regions of like-sign Gaussian curvature. But in strongly active systems, this effect becomes less relevant and defects behave as persistent random-walkers confined in a closed and inhomogeneous space”.

There are many examples of active systems driven by internal activity, including swimming microorganisms, bird flocks, robot swarms and traffic flows. “Active materials are everywhere, so our results aren’t limited to just this system on a torus,” Ellis added. “You could see the same behavior in any active system with defects.”

The research sets the stage for future work in active fluids. “Our results introduce a new framework to explore the mechanical properties of active fluids and suggest that partially ordered active matter can be guided and controlled via gradients in the intrinsic geometry of the underlying substrate,” the authors wrote in a summary of their paper.

This research was supported by the National Science Foundation under award 1609841 and the Netherlands Organization for Scientific Research. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsoring agencies.

CITATION: Perry W. Ellis, Daniel J. G. Pearce, Ya-Wen Chang, Guillermo Goldsztein, Luca Giomi, and Alberto Fernandez-Nieves, “Curvature-induced Defect Unbinding and Dynamics in Active Nematic Toroids,” (Nature Physics, 2017). http://dx.doi.org/10.1038/nphys4276

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Media Relations Contact: John Toon (404-894-6986) (jtoon@gatech.edu).

The researchers who built the program at the Georgia Institute of Technology would like cancer fighters to take it for free, or even just swipe parts of their programming code, so they’ve made it open source. They hope to attract a crowd of researchers who will also share their own cancer and computer expertise and data to improve upon the program and save more lives together.

The researchers’ invitation to take their code is also a gauntlet.

They’re challenging others to come beat them at their own game and help hone a formidable software tool for the greater good. Not only the labor but also the fruits will remain openly accessible to benefit the treatment of patients as best possible.

“We don’t want to hold the code or data for ourselves or make profits with this,” said John McDonald, the director of Georgia Tech’s Integrated Cancer Research Center.  “We want to keep this wide open so it will spread.”

The goods

Researchers wanting to participate can follow this link to a new study published on October 26, 2017, in the journal PLOS One. There they will find links to download the software from GitHub and to access the code.

They’ll start out with a current program that has been about 85% accurate in assessing treatment effectiveness of nine drugs across the genetic data of 273 cancer patients. The study by McDonald and collaborator Fredrik Vannberg details how and why.

“Nine drugs are in the published study, but we’ve actually run about 120 drugs through the program all total,” said Vannberg, an assistant professor in Georgia Tech’s School of Biological Sciences.

The program uses proven machine learning mechanisms and also normalizes data. The latter allows the machine learning to work with data from varying sources by making them compatible.

The bias

And the researchers have reduced human bias about which data are important for predicting outcomes.

“It’s much more effective to put in loads of raw data and let the algorithm sort it out,” McDonald said. “It’s looking for correlations, not causes, so it’s not good to preselect data for what you suspect are most relevant.”

One big bias the researchers tossed out was a concentration only on gene expression data pertaining to the specific type of cancer they were aiming to treat.

“It turns out that it’s better to give the program data from a broad diversity of cancers, and that will actually later give a better prediction of drug effectiveness for a specific cancer like breast cancer,” Vannberg said.

“On a molecular level, some breast cancers, for example, are going to be more similar to some ovarian cancers than to other breast cancers,” McDonald said. “We just let the algorithm work with about everything we had, and we got high accuracy.”

The winners

The researchers also want the project to pool large amounts of anonymous patient treatment success and failure data, which will help the program optimize predictions for everyone’s benefit. But that doesn’t mean some companies can’t benefit, too.

“If a company comes along and makes profits while using the program to help patients, that’s fine, and there’s no obligation to give back to the project,” said McDonald, who is also a professor in Georgia Tech’s School of Biological Sciences. “Others may just take if they so please.”

But hopefully, most players will catch the spirit of kindness.

“With our project, we’re advertising that sharing should be what everybody does,” Vannberg said. “This can be a win for everybody, but really it’s a win for the cancer patients.”

Also READ: Basic premise in targeted cancer treatments wrong 60% of the time

Georgia Tech researchers Cai Huang and Roman Mezencev coauthored the study. The research was funded by the Rising Tide Foundation.

Investigators from the Georgia Institute of Technology and the University of Michigan reported this research October 23 in the journal Nature Cell Biology. The research, done in an animal model, was supported by the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Regenerative Engineering and Medicine Research Center operated by Emory University, Georgia Tech and the University of Georgia. 

The authors used the engineered hydrogels to create a 3D growth environment – known as a matrix – which provides optimal physical and biochemical support for organoid growth. Earlier approaches to creating this growth environment, pioneered by study co-author Jason Spence, Associate Professor of Internal Medicine at the University of Michigan, had used a natural matrix derived from a tumor cell line. The use of animal products is a significant clinical challenge due to potential zoonotic infections, which can be spread from animals to humans. 

“The use of a mouse tumor-derived matrix would limit any future applications of these organoid technologies in humans, and this work opens the door to research directed specifically for clinical applications,” noted Asma Nusrat, study co-author and the Aldred Scott Warthin Professor and Director of Experimental Pathology in the University of Michigan’s School of Medicine. 

In addition to allowing growth of organoids within the engineered hydrogel in a tissue culture incubator, the research team demonstrated that the hydrogel could act like glue, allowing organoids to stick in place and contribute to wound healing when transplanted into an injured mouse intestine. The success could point the way to a new type of therapy aimed at repairing intestinal damage in humans, and potentially for repairing damage in other organs.

“We have shown that the hydrogel matrix helps the human intestinal organoids (HIOs) engraft into the intestinal tissue, that they differentiate and accelerate the healing of the wound,” said Andrés J. García, Regents’ Professor in Georgia Tech’s Woodruff School of Mechanical Engineering. “This work provides a proof of principle for using stem cell-derived human intestinal organoids in a therapeutic setting.”

Because the hydrogels are based on defined synthetic materials, they offer an advantage for potential therapeutic use in the body.

“The fully defined nature of these synthetic bioengineered hydrogels could make them ideal for use in human patients in the event that HIOs are used for therapy in the future,” said Miguel Quirós, a University of Michigan postdoctoral fellow and co-lead author in the study. Added Nusrat: “In this work, we demonstrated that the hydrogels facilitate the transplantation of HIOs into an injured intestine, suggesting that this technique has significant implications for treating intestinal injuries caused by diseases such as inflammatory bowel disease.”

The synthetic matrix, developed at Georgia Tech, can be easily modified to suit the needs of the cells being hosted. For instance, Georgia Tech Graduate Student Ricardo Cruz-Acuña, the paper’s co-lead author, experimented with several combinations before determining that a hydrogel made up of 96 percent water and containing a particular cell adhesion peptide was ideal for the HIOs. 

Using a tiny colonoscope, Quirós and Cruz-Acuña delivered the hydrogel, along with the organoids, into wounds that had been made in the intestines of immune-compromised mice. The implanted cells were labeled so they could be detected later. After four weeks, the HIOs had completely engrafted into the injured area, forming 3D structures resembling normal tissue. The synthetic hydrogel had disappeared, replaced by natural extracellular matrix produced by the cells themselves.

“Because our hydrogel system is easily modified, we can just alter other parameters to create the mechanical and biological properties desired to support many types of cells or organoids,” said García, who holds the Rae S. and Frank H. Neely Chair. “The specifics may be different for other cells intended for different applications.”

As next steps, the researchers would like to test their hydrogel matrix in animals with normal immune systems and in disease models. They may also need to optimize the method for delivering the hydrogel material containing the HIOs to replace the labor-intensive techniques used in the research. García, Nusrat and Spence expect that trials in large animals would likely be needed before any human trials could be considered.

Beyond the intestinal applications, the researchers are also studying the use of hydrogels to deliver organoids to damaged kidneys and lungs. 

In addition to those already mentioned, the research team included Priya H. Dedhia, Sha Huang, Vicky García-Hernández, Alyssa J. Miller and Dorothée Siuda at the University of Michigan; and Attila Farkas from the Hungarian Institute of Sciences. 

This research was supported by the NIH (R01 AR062368, R01 AR062920 to A.J.G and R01 DK055679, R01 DK059888, DK055679, DK059888, and DK089763 to A.N.), and J.R.S. is supported by the Intestinal Stem Cell Consortium (U01DK103141), a collaborative research project funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Allergy and Infectious Diseases (NIAID), and by the NIAID Novel, Alternative Model Systems for Enteric Diseases (NAMSED) consortium (U19AI116482), PHS Grant UL1TR000454 from the Clinical and Translational Science Award Program, and a seed grant from the Regenerative Engineering and Medicine Research Center between Emory University, Georgia Tech and the University of Georgia. R.C.A. is supported by a National Science Foundation Graduate Research Fellowship and M.Q. is supported by a fellowship from the Crohn’s and Colitis Foundation of America (CCFA 326912). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsoring agencies.

CITATION: Ricardo Cruz-Acuña and Miguel Quirós et al.,”Synthetic hydrogels for human intestinal organoid generation and colonic wound repair,” (Nature Cell Biology, 2017). https://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3632.html

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Media Relations Contacts: Georgia Tech -- John Toon (404-894-6986) (jtoon@gatech.edu) or University of Michigan Lauren Love (lovelaur@med.umich.edu).

The study is the most detailed picture of cross-border reproductive care (CBRC) in the United States to date. It analyzed more than 1.2 million ART cycles that were submitted to the National ART Surveillance System (NASS) from 2006 to 2013. NASS is the federally mandated reporting system that collects ART procedure information under the Fertility Clinic Success Rate and Certification Act of 1992.

During that time frame, the number of non-residents receiving ART treatment in the United States more than doubled, growing from 1.2 percent of the total number of cases to 2.8 percent (nearly 5,400 in 2013).

“While the number of cycles is relatively small, it is definitely growing,” said Georgia Tech’s Aaron Levine, the associate professor in the School of Public Policy who led the study. “Non-U.S. residents are increasingly coming here for specialized ART treatments that may not be available in their home countries. And they’re using these techniques at greater rates than Americans.”

Non-resident cycles had a higher use of oocyte (or egg) donation (42.6 percent vs. 10.6 percent of American cycles). They were also nearly eight times more likely (12.4 percent vs. 1.6 percent) to use gestational carriers/surrogates, and almost four times more likely to receive preimplantation genetic diagnosis or screening (19.1 percent vs. 5.3 percent).

American and non-American patients had similar embryo transfer and multiple birth rates.

Patients from 147 countries received care in the U.S., with the largest number coming from Canada. Nearly 50 percent of Canadian patients used donated eggs, likely reflecting Canadian legal restrictions on payment for egg donors. Patients from the United Kingdom and Japan, the third and fourth most common source countries, also made frequent use of donated eggs — more than 50 percent of U.K. patients and more than 90 percent of Japanese patients used this technique. The second largest number of patients came from Mexico, with these patients using specialized techniques at about the same rate as U.S. patients.

Levine admits the numbers are small but not trivial. Data has been limited, and CBRC hasn’t been well studied in the past.

“Our results highlight real challenges for patients to access this important medical care,” said Levine. “Understanding these challenges is critical to improving access to ART today and to helping ensure patients who travel across borders to receive ART treatment receive high-quality care.”

Levine also says understanding CBRC ties into other issues, such as treatment for egg donors and carriers, and the health concerns that may be linked to some ART procedures.

The paper, “Assessing the use of assisted reproductive technology in the United States by non-United States residents,” was published online in the journal Fertility and Sterility earlier this month.

The pair met through a first-of-its-kind traineeship in health care robotics offered by Georgia Tech and Emory University. The National Science Foundation (NSF) funded Accessibility, Rehabilitation and Movement Science (ARMS) Traineeship Program is a unique opportunity for engineering students to learn the particulars of health care robotics technologies in the places they are actually used—health care facilities and hospitals.

Created in partnership with faculty from Emory University and led by Ayanna M. Howard, the chair of the School of Interactive Computing and Linda J. and Mark C. Smith Chair Professor in the School of Interactive Computing and the School of Electrical and Computer Engineering, the two-year program has an interdisciplinary design that integrates engineering, robotics, rehabilitation, neuroscience, physiology, and psychology.

“Besides the really unique immersion experience, we also had a group of people to connect with right at the start of our time at Georgia Tech. Not knowing anyone at a new school can be daunting. ARMS is our little community. We have a lot of fun,” said Fry.

As the program is so new, the first cohort of trainees, which includes Fry and Drnach, consists of just six students. The close-knit group meet monthly, attend courses together, and go on grand rounds at local hospitals and clinics. The students also collaborate and volunteer as subjects for each other’s research. Drnach recalls persuading Fry and another ARMS student to don motion capture suits to test a concept for his research.

“It was pretty funny to see them all lit up. They looked like Christmas trees,” said Drnach.

In addition to their individual research, the ARMS program introduces students to unique clinical experiences in an effort to broaden their horizons and give them hands-on experience with the people their research will eventually serve. Students take a Clinical Experiences for Engineers course during their first or second summer in the program. Trainees participate in one week of clinical rotations where they visit different medical facilities and shadow doctors, surgeons, physical and occupational therapists, and even patients. Students can choose from a variety of clinics to visit including the Shepherd Center, Children’s Healthcare of Atlanta, Emory ALS Center, and the Emory Brain Health Center. These rotations give them the opportunity to make clinical observations on a multitude of health care challenges.

At the end of the course, each student gives a presentation on a clinical need that is identified along with a solution. Fry’s presentation resulted from her work with a speech therapist at the Emory ALS Clinic. The project involved customizing a text-to-speech device that matched the sound of the patient’s actual voice—a humanizing improvement over the robotic voice currently used in such technology.

For his final presentation, Drnach conceived of a solution to a common problem experienced by those with Parkinson’s disease. Through shadowing a patient, Drnach learned that many Parkinson’s patients have trouble regulating the volume of their speech in relation to ambient noise. His device would give the user a physical cue to let them know if they needed to quiet down or speak louder based on their surroundings.

Fellows in the program are funded through ARMS for the first two years of their Ph.D. This is a nice perk according to Drnach, as it provides the flexibility to work with a variety of faculty members and do lots of interdisciplinary research before settling into a particular research group.

The program actually gave Drnach a different perspective on his studies and he ended up changing the direction of his research. Coming from an undergraduate bioengineering program, his experience had been more user focused. He finds that his interest now lies in more traditional engineering challenges having to do with the mechanics and controls of machines and devices. 

“I like the idea of fusing the knowledge of how people behave with how robots behave and creating solutions to problems. I can take all the technical classes I want and then apply them to projects that have a humanitarian purpose,” said Drnach.

Drnach’s home school is ECE and he is advised by Lena Ting, a specialist in neuromechanics and a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. Currently, his research focuses on a “robotic gait coach” that helps elderly patients learn to adjust their walking patterns to improve strength and balance.

One goal of the program is to set up students with a main advisor in engineering and a co-advisor who focuses on medical research. For example, Fry is advised by Professor Ayanna Howard in ECE and Dr. Yu-Ping Chen in the Georgia State University Department of Physical Therapy and the Center for Pediatric Locomotion Sciences. Dr. Chen’s research involves early detection of cerebral palsy in infants. Fry is working on developing a system that gathers data from sensors attached to a baby’s legs as they kick. Based on patterns in movement, the hope is that one day a reliable test can be created to detect the disease in the first few months of life, enabling early intervention and treatment.

“Yes, I get to work with real babies. No, I don’t have to change diapers. I also use a NAO robot to simulate kicking. Oh—and I have a kicking baby doll! Her name is Babby. I love her,” said Fry.

Fry chose Georgia Tech because of its reputation in robotics research, but the tipping point that made Georgia Tech the best choice over other programs was ARMS.

“The opportunity to work very closely with the people who would ideally be the end users of your research—that was a big draw. The friends that I’ve made through ARMS are the icing on the cake.” said Fry.

The ARMS Program is currently looking to expand and engage with more students and faculty advisors. To learn more visit the ARMS website.

The National Institutes of Health has awarded Kim over $2.3 million in funding to boost his innovative research using life-mimicking laboratory chips to explore the treatment of atherosclerosis. No other health hazard appears to be deadlier, as the condition is also behind stroke, some chronic kidney diseases, peripheral artery disease, and carotid artery disease.

Known for its high prestige, the NIH Director’s New Innovator Award is one of four High-Risk, High-Reward awards given annually, which recognize promising new projects that address challenges in biomedical research of pressing importance to human health.

Everyone is at risk

We are all at risk for clogged arteries or hardening of the arteries, common terms for atherosclerosis.

If atherosclerosis is detected in time, bypass surgery, drugs that lower bad cholesterol, and lifestyle changes can save lives. But many patients’ conditions worsen in spite of these, and there is a strong need for better treatment options.

Failures in clinical trials of new potential treatments that raise levels of “good cholesterol” have underscored the need for better understanding of the therapeutic role of good cholesterols known as high-density lipoprotein (HDL). They are the focus of the research for which Kim’s grant was awarded.

Bad ‘good cholesterol’

Recently, researchers have uncovered that good cholesterols are not always good. There are thousands of different HDLs, and, take together, they don’t work as they should in patients with coronary artery disease. Some HDLs even do bad things.

“Researchers tried raising HDL levels in patients’ bloodstreams thinking patients’ conditions might improve, but the coronary artery disease did not get better,” said Kim, an assistant professor in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology. “Also, high levels of HDLs in the bloodstream don’t always protect people from atherosclerosis.”

Kim is interested in HDLs’ hit-or-miss qualities in atherosclerosis patients, and in how inflammation leads to HDLs’ diminished effectiveness. Proinflammatory proteins in the bloodstream junk up good HDLs. “HDLs remake themselves all the time, and they can incorporate proinflammatory proteins, which disturb the traditional good cholesterol functions that HDL is known for,” Kim said.

The Kim group could better understand the mechanisms behind that, and also find ways to leverage these for treatments. His team may be able to identify some HDL cocktails that reduce atherosclerosis despite raised proinflammatory proteins levels in the bloodstream of patients with coronary artery disease or chronic kidney disease.

Artery-on-a-chip

Kim’s proposed research that won the NIH award illuminates HDL interactions with proinflammatory proteins and with vascular tissues by mimicking some of them in the lab. Kim makes aspects of these interactions observable via a special slide called a human-coronary-artery-on-a-chip.

It’s a clear plastic chip with microfluidic passages lined with living arterial cells to form an artificial coronary artery. Inside the artificial arteries, Kim’s research group experiments with what are called engineered high-density lipoproteins (eHDLs), nanoparticles synthesized to be near faultless samples of specific HDLs.

Natural HDLs are often not as uniform in composition and size because of interactions with other proteins. On the other hand, Kim’s group can produce eHDLs with uniform properties, allowing for reliable experimental parameters. The eHDLs are highly reproducible, as are the experiments, the latter of which is essential in research for cementing trustworthy results.

Innovative microfluidic technology allows for the robust production of multicomponent nanomaterials, in this case, the eHDLs and inflammatory proteins, in large quantities and varieties. As a result, Kim’s team can compile a comprehensive eHDL library with various functional proteins to see how they affect the artificial artery the way actual HDLs might in combination with inflammatory proteins affect real arteries in the body.

Once the in vitro chip experiments yield results, Kim’s research group will work to corroborate them in vivo in experiments on a mouse model of atherosclerosis in collaboration with cardiology engineering researcher Hanjoong Jo at Emory University School of Medicine.

Atherosclerosis brief description

The old explanation about how cholesterol gunk coats blood vessels like lard is not quite correct, but animal fats are involved in atherosclerosis. Here’s a brief description of how the disease clogs arteries.

Oil and water don’t mix.

So, lipoproteins, which are large collections of particular protein molecules, wrap around lipids, which include oily fats called triglycerides, to transport them through the bloodstream, which is water-based. Some lipoproteins, like the infamous low-density lipoproteins (LDLs), deliver lipids to cells, but HDLs pick them up from cells when it’s time for them to leave and take them to the liver for breakdown, a process called reverse cholesterol transport.

If there aren’t enough well-functioning HDLs in the bloodstream, reverse cholesterol transport can slow down, and the lipids amass in artery walls behind endothelial cells, which make up the lining inside of arteries.

A healthy body maintains a balance between anti-inflammatory and proinflammatory proteins, so normally not too many HDLs are corrupted too badly. But when levels of proinflammatory proteins in the bloodstream rise, more HDLs get corrupted.

As a result, lipids congregate in the arterial wall, along with immune cells that get stuck there, together forming plaque, which causes the arteries to narrow and constrict blood flow. The plaque can burst into the artery, clogging it even more.

A heart attack or stroke can result.

Also READ: Alzheimer's research, its vexing past, its future hopes

High-Risk, High-Reward

The name of the category of the NIH grant Kim received is High-Risk, High-Reward for a reason. The risk refers to a bold move into uncharted territory, according to the NIH.

The potential reward, in this case, could mean discovering new effective treatments against what appears to be the single deadliest killer of our times.

Kim sees high reward potential in the unique possibilities combining the human-organ-on-a-chip technology and the bioinspired nanotechnology provides. “You can’t do this type of work in vivo,” Kim said. “And the high reproducibility is very valuable to sort out truly good candidates for treatment trials.”

Should the experiments result in nailing down a drug candidate, Kim’s lab will leverage its high-throughput manufacturing method to produce ample substances with high consistency for drug testing.

And the high risk in his view?

“Even if we find HDLs with specific functions, they may not work in the same way in our bodies because of HDLs’ compositional and functional complexity. The body can still introduce unidentified proteins into the HDLs,” Kim said. “It’s always like that in human trials. Things we still don’t know about the body’s enormous biochemistry can get in the way.”

“Even so, the experiments may provide unprecedented insights into these complex nanoparticles and still move research forward toward better treatments. I think that, combined with all the engineering and scientific possibilities the work taps into, the high rewards dampen the potential risk.”

The NIH Director’s New Innovator Award covers five years of research funding and is given to a principal investigator who is in an early career stage and has never received a large-category NIH grant before.

Tony Kim is also affiliated with Georgia Tech’s Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, Georgia Tech’s Parker H. Petit Institute for Bioengineering and Bioscience, and Georgia Tech’s Institute for Electronics and Nanotechnology.

Also READ: Successful human trials of painless vaccine you give to yourself: Microneedle patches

This alliance is celebrating 10 years of research advancement by expanding across the state through a five-year, $51 million Clinical and Translational Science Award (CTSA) from the National Institutes of Health (NIH). The Emory University-led Georgia CTSA will focus on transforming the quality and value of clinical research and translating research results into better outcomes for patients.

The Georgia CTSA unites the strengths of its academic partners: Emory University, Morehouse School of Medicine, the Georgia Institute of Technology, and the University of Georgia. Emory is a national leader in health care and biomedical research as well as an outstanding leader in clinical and translational research training and education. Morehouse School of Medicine is a nationally recognized historically black institution that brings ethnic diversity to biomedical research, addresses health disparities through successful community engagement research, and serves as a pipeline for training minority researchers. Georgia Tech is a national leader in biomedical engineering, bioinformatics  and the application of innovative systems engineering to health care solutions. The University of Georgia has a proven track record in outstanding basic and translational research and, as the state’s land grant institution, offers a robust statewide network that enhances community outreach, service and research.

“Continuing such an alliance and involving these leading state institutions is extremely important and in line with Georgia’s goals for the promotion of clinical and translational research, innovation and development,” said Georgia Governor Nathan Deal. “Having an active Clinical & Translational Science awardee in Georgia has brought our citizens cutting edge cures and the latest in clinical and translational research.”

Georgia CTSA is one of 64 Clinical and Translational Science Awards (CTSA) at major academic medical centers across the country, funded by the National Institutes of Health’s National Center for Advancing Translational Science, and it is the only CTSA in Georgia. The award will fund cores focused on improving quality, efficiency and collaboration of the research process; provide consultative support and new tools in informatics and biostatistics; pilot funding for new research projects, training and workforce development, while integrating special populations and focusing on participant interactions, and creating local centers tackling clinical trial inefficiencies.

The Georgia CTSA welcomes contact principal investigator (PI) at Emory, W. Robert Taylor, M.D., Ph.D., and a new multi-PI leadership structure: 

W. Robert Taylor, MD, PhD
Contact Principal Investigator, Georgia CTSA
Interim Chair, Department of Medicine
Director, Division of Cardiology
Marcus Chair in Vascular Medicine
Professor of Medicine and Biomedical Engineering
Emory University School of Medicine

Elizabeth O. Ofili, MD, MPH
Principal Investigator, Morehouse School of Medicine, Georgia CTSA 
Professor of Medicine, Cardiology
Senior Associate Dean of Clinical and Translational Research
Director, Clinical Research Center 
Morehouse School of Medicine

Andrés J. García, PhD
Principal Investigator, Georgia Institute of Technology, Georgia CTSA 
Rae S. and Frank H. Neely Endowed Chair and Regents' Professor, Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience
Director, Interdisciplinary Bioengineering Graduate Program
Georgia Institute of Technology

Bradley G. Phillips, PharmD, BCPS, FCCP
Principal Investigator, University of Georgia, Georgia CTSA
Millikan-Reeve Professor and Head, Clinical & Administrative Pharmacy, College of Pharmacy 
Director, Clinical and Translational Research Unit (CTRU), Office of Research
University of Georgia

Henry M. Blumberg, MD
Principal Investigator, KL2 and TL1, Georgia CTSA
Professor of Medicine and Epidemiology, Division of Infectious Diseases
Emory University School of Medicine

"The Georgia CTSA creates a unique opportunity for synergy among historic partners in health care, education, and cutting edge research, and has emerged as an innovative and integrated environment where clinical and translational researchers can flourish," said Taylor. "The Georgia CTSA is a catalyst and incubator for clinical and translational research across the state, with impacts throughout the Southeast and nation."

The Georgia CTSA has improved health care and research for Georgia citizens through collaboration with the Grady Health System, Children’s Healthcare of Atlanta, Atlanta VA Medical Center, Georgia Research Alliance, Georgia Bio, and multiple community medical groups throughout the state. 

"Georgia CTSA continues established, strong clinical and research partnerships by leveraging the infrastructure support of the NIH-funded Research Centers at Minority Institutions (RCMI) at Morehouse School of Medicine. We will continue to implement innovative patient centered and participatory care delivery models, toward the elimination of health disparities," said Ofili.

“Georgia CTSA’s innovative support of discovery and collaborative partnerships help to rapidly translate scientific discoveries and new technology, which positively impacts patient care in Georgia. This is an exciting story for the state,” said Garcia. “The new alliance is improving health care and clinical research for the citizens of Georgia and continues to create synergies that foster and accelerate new and emerging technologies and discoveries.”

“The addition of the University of Georgia provides the Georgia CTSA a statewide footprint to connect with every county in the state to address health and wellness needs, particularly in rural and underserved populations; opportunities for continued excellence in research by strengthening existing and expanding new research collaborations; and the ability to enrich interprofessional education to include students and trainees from pharmacy and other disciplines so that they can learn how to work together as a team to discover new approaches and treatments that improve health and patient care,” said Phillips. “As a new member of the Georgia CTSA, faculty and students across our campus will have unique support and infrastructure that builds upon current capabilities and increases our trajectory in fostering clinical and translational science in the state and beyond.” 

Written by Georgia Clinical & Translational Science Alliance.

For more information, please visit www.GeorgiaCTSA.org  

It’s a scattered and somewhat inconsistent revolution, however, as some regions with adequate resources set the pace for discovery, while others are left virtually stranded. Such is the case on the African continent, where many countries are being left behind, a situation that has the potential of widening global and ethnic inequalities in health and economic well-being.

Fortunately, though, a collection of individuals and institutions, including the Georgia Institute of Technology, are responding to the challenge and working to bridge the genomic divide. It’s the kind of bridge-building that King Jordan, a researcher with the Petit Institute for Bioengineering and Bioscience, has grown accustomed to. His lab, and the Bioinformatics Graduate Program that Jordan directs, have been deeply engaged in biotechnology capacity-building efforts in Latin America for close to a decade.

“We’re leveraging bioinformatics and genomics technologies to facilitate public health and to stimulate economic development overseas,” says Jordan, associate professor in the School of Biological Sciences, who cites the Georgia Tech strategic vision plan laid out in 2010, specifically goal number four, which involves expanding Tech’s global footprint and influence.

“That is done in two ways,” says Jordan. “One is by bringing the world to Georgia Tech and training more globally-engaged students. The other way is to project Georgia Tech’s reach out to the world, and we’re doing both.”

And now it’s happening in Africa, with the recent announcement that Jordan and one of his former grad students, Daudi Jjingo, have been awarded a five-year, $1.3 million grant as part of the NIH’s Human Heredity and Health in Africa (H3Africa) Initiative. H3Africa aims to elucidate Africa’s human genetic diversity (the highest on the planet) and thus one with a high potential of revealing more varied ways in which the human genome interacts with diseases and other environmental pertubations.

The plan is to use the award to support two trajectories, according to Jjingo, who earned his PhD as a Fulbright fellow in Jordan’s research team at Georgia Tech in 2013 and returned to his home country, Uganda, where he is a faculty researcher at Makerere University in Kampala.  

“First we want to focus on building a computing and physical infrastructure, and secondly, we want to actually start a bioinformatics program,” says Jjingo. “The idea is to build a sustainable bioinformatics program.”

There is a lot of clinical research happening now in Africa, Uganda in particular, Jjingo says, and researchers currently lack the bioinformatics resources to adequately analyze all of that data.

“So the vision is, at the end of five years we’ll have this program established, well-staffed, with students graduating,” Jjingo says. “Having talented students who graduate creates the infrastructure – it builds the right recipe to build a research center, which means we can move beyond academia and provide bioinformatics consulting services for industry and others.”  Their bioinformatics consulting efforts will be modeled after the Applied Bioinformatics Laboratory (ABiL), a public-private partnership between the Jordan lab at Georgia Tech and the company IHRC Inc., which provides bioinformatics analysis services and training to industry and non-profit clients.

The program in Uganda will begin, Jjingo says, “with about five Masters students and a couple of PhD students, and the plan is that one of them will spend a year at Georgia Tech – from my own experience, I know the huge value you can get by spending a short time there, learning from a mature research environment and ecosystem. And Georgia Tech personnel will come here to Uganda, to conduct short seminars, and so forth. So we’re talking about an exchange of human resources.”

Jordan adds, “one thing we know that is implicit in the notion of mentoring a grad student is the idea of collaborative research. So when you have a graduate student that serves as the fulcrum between two institutions, it provides a great opportunity build bridges. My hope is that those students will engage in collaborative research that will allow for deeper connections between Georgia Tech and Makerere University.”

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

The researchers aim to identify metabolic features in head and neck cancers that are predictive of tumor response to a new chemotherapeutic drug, ß-lapachone, currently in clinical trial at the University of Texas-Southwestern (UTSW). Fellow leaders of the project are David Boothman, Ph.D., from the UTSW Medical Center and Cristina Furdui, Ph.D., from the Wake Forest School of Medicine.

Joshua Lewis, an Emory M.D./BME Bioinformatics Ph.D. student in Kemp’s lab, developed a genome-wide model of metabolism in head and neck cancer that explained why the cytotoxicity to ß-lapachone differed between radiation-sensitive and radiation-resistant cancer cells.

The research team identified new molecular targets for enhancing cell death with the drug—validating the results with a 332 gene RNAi screen. The modeling analysis suggests that the radiation-resistant cells rerouted metabolism and altered the enzymatic cycling of ß-lapachone, rendering them more susceptible to the chemotherapy.

“I’ve learned through this project how devastating head and neck cancer (HNC) is for patients, and the incidence of HNC is particularly high here in the Southeast compared to the rest of the US,” said Kemp, a researcher with the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

“There are very few FDA-approved drugs for HNC and the survival rate for the late-stage cancer patients we are examining has been relatively stagnant for the past three decades," Kemp added. “Our goals are to develop computational models that factor in patient-to-patient variability in HNC metabolism and use these tools to predict who will respond well to the new ß-lapachone therapies.”

Head and neck cancers include cancers of the larynx (voice box), throat, lips, mouth, nose, and salivary glands.

As part of the award, the researchers will join and participate in the NCI Cancer Systems Biology Consortium. The multidisciplinary Cancer Systems Biology Consortium, funded by the National Cancer Institute, aims to tackle the most perplexing issues in cancer to increase our understanding of tumor biology, treatment options, and patient outcomes.

Media Contact:

Walter Rich
Communications Manager
Wallace H. Coulter Department of Biomedical Engineering

By analyzing the rules governing the locomotion of these creatures, "physics of living systems" researchers are learning how animals successfully negotiate unstable surfaces like wet sand, maintain rapid motion on flat surfaces using the advantageous mechanics of their bodies, and fly in ways that would never work for modern aircraft. The knowledge these researchers develop could be useful to the designers of robots and flying vehicles of all kinds.

“Locomotion is a very natural access point for understanding how biological systems interact with the world,” said Simon Sponberg, an assistant professor in the School of Physics and School of Biological Sciences at the Georgia Institute of Technology. “When they move, animals change the environment around them so they can push off from it and move through it in different ways. This capability is a defining feature of animals.”

Sponberg has spent his career bridging the gap between physics and organismal biology – the study of complex creatures. His work includes studying how hawk moths slow their nervous systems to maintain vision during low-light conditions, and how muscle is a versatile material able to change function from a brake to a motor or spring.

He recently published a feature article, the cover story for the September issue of the American Institute of Physics magazine Physics Today, on the role of physics in animal locomotion. The article was not intended as a review of the entire field, but rather to show how organismal physics – integrating complex physiological systems, the mechanics and the surrounding environment into a whole animal – has inspired his career.

“The intersection of physics and organismal biology is a very exciting one right now,” said Sponberg, who is also a researcher with the Petit Institute for Bioengineering and Bioscience at Georgia Tech said. “The assembly and interaction of multiple natural components manifests new behaviors and dynamics. The collection of these natural components manifests different patterns than the individual parts, and that’s fascinating.”

Supported by new initiatives at such organizations as the Army Research Office/Army Research Laboratory and the National Science Foundation – which are embracing these frontiers – Georgia Tech scientists are learning the equations that dictate how snakes move, understanding how the hair spacing on the bodies of bees help them stay clean, and using X-ray equipment to see how an unusual African lizard “swims” through dry sand.

“It’s a really exciting time to be working at the intersection of evolutionary organismal biology that is realized in these living systems that have come about through the process of evolution, composed of seemingly very complex systems,” he said. “Biological systems are inescapably complex, but that doesn’t mean there aren’t simple patterns of behavior that we can understand. We now have the modern tools, approaches and theory that we need to be able to extract physical patterns from biological systems.”

In his article, Sponberg makes predictions about the research that will be needed for the physics of living systems to advance as a field:

• How feedback transforms physiological dynamics,
• How aggregations of living components, from humans to ants to molecular motors, arise at multiple scales, and
• How robo-physical models of these complex systems can lead to new discoveries and advance engineering.

Engineered systems use feedback about the effects of their actions to adjust their future activities, and animals do the same to control their movement. Scientists can manipulate this feedback to understand how complex systems are put together and use the feedback to design experiments rather than just analyzing what is there. 

“We use feedback all the time to move through our environment, and feedback is a really special thing that fundamentally affects how dynamics occur,” said Sponberg. “But using feedback to design experiments is really sort of new.”

For example, in the study of how hawk moths track flowers during low-light conditions, he and his colleagues used feedback dynamics to isolate how the moth’s brain adjusts its processing in dim light. The moths can still accurately track flower movements that occur less than two times per second – which matches the frequency at which the flowers sway in the wind.

Animals are composed of many systems operating at multiple time scales simultaneously – brain neurons, nerves and the individual fibers of muscles with molecular motors. These muscle fibers are arranged in an active crystalline lattice such that X-rays fired through them create a regular diffraction pattern. Understanding these multiscale living assemblages provides new insights into how animals manage complex actions.

Finally, Sponberg notes in his article that robots are playing a larger and larger role in the physics laboratory as functional models that can examine principles of movement by interacting with the real world. In the laboratory of Georgia Tech Associate Professor Dan Goldman – one of Sponberg’s colleagues – robotic snakes, turtles, crabs and other creatures help scientists understand what they’re observing in the natural world.

“Moving physical models – robots – can be very powerful tools for understanding these complex systems,” Sponberg said. “They can allow us to do experiments on robots that we couldn’t do on animals to see how they interact with complex environments. We can see what physics in these systems is essential to their behaviors.”

Sponberg was inspired to study the interaction of organismal biology and physics by the remarkable diversity of animal movement and by nonlinear dynamics, a field made popular when he was a young student by the 1987 best-selling book Chaos: Making a New Science, authored by former New York Times reporter James Gleick. Sponberg hopes today’s students – readers of Physics Today – will also be inspired.

“I voted on this with my career choice, so I think this is a very exciting areas of science,” he added.

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Writer: John Toon

The inaugural BioInnovation Showcase (August 31) at the Petit Institute for Bioengineering and Bioscience provided the opportunity to see what happens when that potential is realized, as 20 companies at different stages of development, set up shop in the atrium, highlighting their products for more than 130 invited guests.

“This is a first, a bit of an experiment, and I hope you all enjoy it,” Petit Institute Executive Director Bob Guldberg told guests at the outset of the showcase. “I think everybody in this room appreciates the challenge of taking research from a lab and turning that into a successful company. It’s huge a leap.”

Georgia Tech President Bud Peterson helped kick off the event, saying the showcase fit in perfectly with, “what’s been happening here at Georgia Tech for some time, maybe the last 10 or 12 years, and that is a real strong focus on innovation and entrepreneurship.”

But the highlight was the showcase itself, the 20 bio-companies spread out in the atrium, demonstrating the novel ideas that have made (or, are in the process of making) the transition from the lab to viable businesses designed to improve patient health, increase energy production, or feed the world.

For example, there was Grubbly Farms, founded by Georgia Tech graduates, who formed the company to combat the rising cost of livestock feed through the growth and processing of black soldier fly larvae, which are then dried to become ‘Grubblies,’ an eco-friendly food source for chickens.

There was Axion Biosystems, a thriving business founded by former Georgia Tech biomedical engineering student James Ross, who started developing the company’s patented microelectrode array technology with fellow students while still at Tech.

And there was Dikaryon, a company born in the mountains of Montana, where Frank Rosenzweig, now a professor in the School of Biological Sciences and a Petit Institute researcher, initially developed the technology. “I started this at the University of Montana and brought it here to Atlanta, and Georgia Tech has recently filed a provisional patent,” said Rosenzweig.

Dikaryon aims to, “help ethanol companies produce ethanol more efficiently,” according to Jordan Gulli, a graduate student in Rosenzweig’s lab. “We do that by improving the fermentation step. This could be used to improve other processes as well, anything you make with synthetic biology, such as vaccines, insulin, industrial lubricants – tons of products.”

Meanwhile, across the atrium from where Gulli was demonstrating the chemical process that makes Dikaryon a worthwhile endeavor, Rafael Andino was talking about his company’s thrilling future. Clearside Biomedical’s first drug is in Phase 3 clinical trials.

“Our drug treats two diseases of the eye that, if left untreated, will cause blindness,” said Andino, vice president of engineering and manufacturing, and adjunct professor in the Coulter Department of Biomedical Engineering. “This is a very exciting time for us, we have studies going on now around the world.”

Ultimately, though, as Guldberg explained, “this is just the tip of the iceberg of what is coming down the line.”

Partnerships, he said, and the multi-disciplinary approach the Petit Institute has become known for, continue to inspire and drive the kind of innovations that become a commercial success. He spotlighted the ongoing, fruitful partnership with Emory University, for instance, and presence at the showcase of industry partners like Boston Scientific, Boehringer Ingelheim Animal Health, and event sponsor, Flad Architects (who designed the Petit Biotechnology Building, where all of this was happening). Underlying much of that, he noted, are agencies that support early-stage efforts, organizations like Georgia Tech’s VentureLab and the Georgia Research Alliance.

It always comes back to the collection of parts (and not the parts themselves) working in concert. It always comes back to collaboration.

“Collaboration,” Guldberg said, “is the real driver for biotech innovation, and for the truly transformative work going on now in our labs.”

Showcased companies:

Axion Biosystems

Bioscents

BWHealth

CellectCell, Inc.

Clean Hands – Safe Hands

Clearside Biomedical, Inc.

DETECT

Dikaryon Biotechnologies

FraudScope

Grubbly Farms

Lena Biosciences

Lymphatech

Microfluidic Systems for Cell Engineering and Analysis

Micron Biomedical, Inc.

Nanodigm

PanXome

Sanguina, LLC

Sophia Bioscience

Robotic Guidewire

Vertera Spine

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

In nature, evolution is manifested in the progression of changes in the genetic composition of all organisms over generations as they adapt to altered living conditions. Researchers have been studying nature’s process of change for more than a century in a desire to understand it and, in the lab, control or direct evolution at the molecular level at an unprecedented rate.

Molecular evolution (the process of evolution at the DNA, RNA, and protein level) emerged as a field in the 1960s, so it’s inevitable that the field itself has also evolved.

“Over the past 30 years or so, scientists have figured out how to use some of the mechanisms that biology uses for evolution – extracting the tools for evolving molecules out of biological systems and putting them into the hands of laboratory investigators,” says M.G. Finn, professor and chair in the School of Chemistry and Biochemistry at the Georgia Institute of Technology, and a researcher with the Petit Institute for Bioengineering and Bioscience.

“We’ve learned how to bring that knowledge into the lab, and those techniques are now routine, and reasonably easy to use once you know how,” says Finn, who first proposed the creation of the Molecular Evolution core facility, which launched last year in the Roger A. and Helen B. Krone Engineered Biosystems Building.

But the techniques are still advanced enough so that most biomedical researchers don’t actually have the know-how. That’s where the Molecular Evolution core comes in. While most core facilities are built around sophisticated equipment, this one is centered on the design and execution of experiments that involve molecular evolution techniques, such as phage display, SELEX, and yeast hybrid selection methods, which provide access to peptides, proteins, and polynucleotides with an immense range of properties.

“We can train people to do simple molecular evolution,” says Anton Bryksin, technical director and day-to-day manager of the Molecular Evolution core. “My basic mission is to train students, post-docs and research scientists across campus in applying these molecular evolution techniques to their own work.”

To be sure, the sophisticated equipment is there in the 1,000-square-foot facility: next generation sequencing (NGS) machines (Illumina MiniSeq and NextSeq500), a QPix II colony picker, BluePippin Pulse Electrophoresis system, Bioanalyzer 2100, and a Beckman Coulter Z2 cell and particle counter, among other things.

“Our services are demand-driven, by researchers from across campus, and also driven by my own research,” says Bryksin, whose current work is focused on bacterial surface display that allows efficient expression of different proteins on the surface of bacterial cells. “Cells expressing proteins on their surface can be used to produce small particles – outer membrane vesicles, or OMVs, that also contain biologically active proteins. We are now trying to see whether OMVs can be used as delivery vehicles to bring biologically active proteins toward specific targets.”

Meanwhile, Bryksin and lab technician Naima Djeddar, are helping to guide a number of different Petit Institute researchers in the techniques involved in directing the evolution of molecules. An evolutionary process that takes generations in nature, may take only days with skilled direction.

“The Molecular Evolution core is somewhat different, in that techniques are chosen for the problem at hand, and then investigators are trained in whichever of those are most appropriate,” Finn says.

Prospective core users can submit their request and expect high quality results with a relatively quick turnaround time, according to Steve Woodard, assistant director/core facilities, who oversees core facilities in the Petit Institute.

“Phage display is one of the services that makes the molecular evolution core unique and valuable on the Georgia Tech campus, and in the region,” Woodard says. “Dr. Bryksin also has the ability to aid the evolutionary selection with in-silica analysis, thus rationally designing selection libraries in the computer, producing them, and then testing their binding or other properties.”

Directing the evolution of something takes a lot of technical skill. The researchers who could take advantage of such skills are wide ranging, but would include anyone making a nanoparticle that targets a specific cell type or a molecule that binds to a particular protein.

“In our own lab, we’re trying to evolve a new class of enzymes, which uses the same kinds of tools and designs,” Finn says. “When you start thinking about designing experiments using evolutionary tools, you find the same principles come up over and over again.”

He believes it be the first and only core facility devoted to the techniques of molecular evolution in the U.S., and perhaps the world.

“I can’t emphasize enough the essential role that the Georgia Tech’s administrative leaders played in building this core,” Finn says. “When the idea was presented, they were open and perceptive. The response was remarkable. As a result, now we have a powerful set of new tools at our disposal. It will be interesting to see where we evolve to from here.”

LINKS

Molecular Evolution core

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

Sulchek, an associate professor of bioengineering in the Woodruff School of Mechanical Engineering, shares the $90,000 grant with his collaborators, Young-sup Yoon from Emory University and James Lauderdale from the University of Georgia (UGA).

The title of their research is, “Microfluidic Technologies for Improved Engineering of iPSCs and Their Applications to Treating Corneal and Lymphatic Diseases.” The goal is to analyze and validate a mechanical method to deliver reprogramming factors to human somatic cells, creating induced pluripotent stem cells (iPSCs) that would potentially be used, down the road, in the treatment of lymphedema, cancer, and eye disorders.

Earlier this year, Dr. Allen announced a $1 million gift that would be disbursed over a 10-year period, to the Georgia Research Alliance to advance cell-manufacturing related research and development at Emory, Georgia Tech, and UGA. The gift creates a unique partnership designed to accelerate collaboration, stimulate innovation, and help establish Georgia as a leader in cellular manufacturing.

Seed grant teams must have researchers from each institution, and the award is divided equally between the three schools. The award supports collaborative projects with a high potential for clinical or industry translation at earlier stages of development.

Ancestors of the first protein molecules, which are key components of all cells, could have been bountiful on pre-life Earth, according to a new study led by researchers at the Georgia Institute of Technology, who formed hundreds of possible precursor molecules in the lab. Then they meticulously analyzed the molecules with latest technology and new algorithms.

They found that the molecules, called depsipeptides, formed quickly and abundantly under conditions that would have been common on prebiotic Earth, and with ingredients that would have likely been plentiful.

And some of the depsipeptides evolved into new varieties in just a few days, an ability that, eons ago, could have accelerated the birth of long molecules, called peptides, that make up proteins.

Without cataclysm, please

The new NASA-affiliated research adds to a growing body of evidence suggesting that the first polymers of life may have arisen in variations of daily processes still observed on Earth today, such as the repeated drying and refilling of pond water. They may not have all zapped into existence as a result of blazing cataclysms, an image often associated with the creation of the first chemicals of life.

“We want to stay away from scenarios that are not readily possible,” said Facundo Fernández, a professor in Georgia Tech’s School of Chemistry and Biochemistry, and one of the study’s principal investigators. “Don’t deviate from conditions that would have been realistic and reasonably common on prebiotic Earth. Don’t invoke any unreasonable chemistry.”

Scientists have long puzzled over how the very first proteins formed. Their long-chain molecules, polypeptides, can be tough to make in the lab under abiotic conditions.

Some researchers have toiled to build tiny chains, or peptides, sometimes under more extreme scenarios that probably occurred less often on early Earth. The yields have been modest, and the resulting peptides have had only a couple of component parts, whereas natural proteins have a large variety of them.

Step-by-step evolution

But complex molecules of life likely did not arise in one dramatic step that produced final products. That’s the hypothesis that drives the research of Fernández and his colleagues at the NSF/NASA Center for Chemical Evolution, headquartered at Georgia Tech and based on close collaboration with the Scripps Research Institute.

Instead, multiple easier chemical steps produced plentiful in-between products that were useful in subsequent reactions that eventually led to the first biopolymers. The depsipeptides produced in this latest study could have served as such a chemical stepping stone.

They look a lot like regular peptides and can be found today in biological systems. “Many antibiotics, for example, are depsipeptides,” Fernández said.

Fernández, his Georgia Tech colleagues Martha Grover and Nicholas Hud, and Ram Krishnamurthy from Scripps published their study on August 28, 2017, in the journal Proceedings of the National Academy of Sciences. First author Jay Forsythe, formerly a postdoctoral researcher at Georgia Tech, is now an assistant professor at the College of Charleston. Research was funded by the National Science Foundation and the NASA Astrobiology Program.

The new study joins similar work about the formation of RNA precursors on prebiotic Earth, and about possible scenarios for the formation of the first genes. The collective insights may someday help explain how first life arose on Earth and also aid astrobiologists in determining the probability of life existing on other planets.

Understanding depsipeptide Lego

To understand depsipeptides and the significance of the researchers’ results, it’s helpful to start by looking at peptides, which are chains of amino acids. When the chains get really long they are called polypeptides, and then proteins.

Living cells have machinery that reads instructions in DNA on how to link up amino acids in a specific order to build very specific peptides and proteins that have functions in a living cell. For a protein to have function in a cell, its polypeptide chains have to clump up like sticky yarn to form useful shapes.

Before cells and DNA existed on an Earth devoid of life, for polypeptides to form, amino acids had to somehow jostle together in puddles or on the banks of rivers or lakes to form chains. But peptide bonds can be tough to form, especially long chains of them.

Amino stand-in double

Other bonds, called ester bonds, form more easily, and they can link up amino acids with very similar molecules called hydroxy acids. Hydroxy acids are so much like amino acids that they can, in some cases, function as their stand-in doubles.

The researchers mixed three amino acids with three hydroxy acids in a water solution and they formed depsipeptides, chains of amino acids and hydroxy acids held together by intermittent ester and peptide bonds. The hydroxy acids acted as an enabler to put the chains together that would have otherwise been difficult to form.

The primordial soup may have lapped its depsipeptides onto rocks, where they dried out in the sun, then rain or dew dissolved them back into the soup, and that happened over and over. The researchers mimicked this cycle in the lab and watched as the depsipeptide chains further developed.

Death Valley heat

“We call it an environmental cycling approach to making these early peptides,” said Fernández, who is Vasser Woolley Foundation Chair in Bioanalytical Chemistry. Like nature: Make the soup, dry it out, repeat.

In the lab, the drying temperature was 85 degrees Celsius (185 degrees Fahrenheit), although the reaction has been shown to work at temperatures of 55  and 65 degrees Celsius (131 to 149 degrees Fahrenheit). “If you think about early Earth having a lot of volcanic activity and an atmospheric mix that promoted warming, those temperatures are realistic on many parts of an early Earth,” Fernández said.

Early Earth took hundreds of millions of years to cool, and temperatures in the hundreds of degrees are hypothesized to have been commonplace for a long time. Even today, the hottest deserts can reach over 55 degrees Celsius.

Ester do-si-do

Since ester bonds break more easily, in the experiment, the chains tended to come apart more at the hydroxy acids and hold together between the amino acids, which were connected by the stronger peptide bonds. As a result, chains could re-form and link up more and more amino acids with each other into sturdier peptides.

In a kind of square-dance, the stand-in hydroxy acids often left their amino acid partners in the chain, and new amino acids latched onto the chain in their place, where they held on tight. In fact, a number of the depsipeptides ended up being composed almost completely of amino acids and had only remnants of hydroxy acids.

“Now we know how peptides can form easily,” Fernández said. “Next, we want to find out what’s needed to get to the level of a functional protein.”

READ: Possible precursor of RNA forms spontaneously in water

10,000,000,000,000 depsipeptides

To identify the more than 650 depsipeptides that formed, the researchers used mass spectrometry combined with ion mobility, which could be described as a wind tunnel for molecules. Along with mass, the additional mobility measurement gave the researchers data on the shape of the depsipeptides.

Algorithms created by Georgia Tech researcher Anton Petrov processed the data to finally identify the molecules.

To illustrate how potentially bountiful depsipeptides could have been on prebiotic Earth: The researchers had to limit the number of amino acids and hydroxy acids to three each. Had they taken 10 each instead, the number of theoretical depsipeptides could have climbed over 10,000,000,000,000.

“Ease and bounty are key,” Fernández said. “Chemical evolution is more likely to progress when components it needs are plentiful and can join together under more ordinary conditions.”

Also READ: Was the Secret Spice in Primal Gene Soup a Thickener?

Also READ: The work of the NSF/NASA Center for Chemical Evolution

Georgia Tech’s Calvin Millar and Sheng-Sheng Yu also coauthored this study. The research was funded by the National Science Foundation and the NASA Astrobiology Program, under the NSF/NASA Center for Chemical Evolution (CHE-1504217). Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsoring agencies.

Ethier, a Georgia Research Alliance Eminent Scholar in Biomechanics and Mechanobiology, studies the biomechanics and mechanobiology of cells, tissues and organs, with the goal of understanding how cells respond to mechanical stimuli, and how this response in turn affects the function and properties of tissues and organs. His lab research focus areas are glaucoma, a common cause of blindness; and VIIP, a condition that affects astronaut health in long-duration space missions.

Fellow status is awarded to Society members who demonstrate exceptional achievements in the field of biomedical engineering, and a record of membership and participation in the Society.
 

This year's class includes 20 members who were nominated by their peers. 

“This year's class truly exemplifies what it means to be a BMES Fellow. In addition to conducting ground-breaking research, BMES Fellows are leaders in education, promoting diversity and supporting all fields of science.” said Lori Setton, BMES President.

BMES Fellows are invited to pursue leadership positions within the Society and work to improve the future of BMES. Fellows also play an integral role in supporting the field of biomedical engineering.

The Class of 2017 joins 124 other BMES Fellows who have been recognized for their outstanding work and leadership.

The Class of 2017 Fellows will be recognized during the BMES Annual Meeting held this October 11-14, in Phoenix.

The new research center at the Georgia Institute of Technology is partnering with Emory University, Children’s Healthcare of Atlanta, and Morehouse School of Medicine, and is led by Jaydev Desai, professor in the Wallace H. Coulter Department of Biomedical Engineering (a joint department of Georgia Tech and Emory University). Desai is also the associate director of the Institute for Robotics and Intelligent Machines (IRIM) leading the medical robotics and human augmentation area, and a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

Desai’s lab is a place where tiny technology is being used to foster big ideas, where small robots are being designed to carry out great tasks that would improve the lives of patients and the clinicians who treat them.

“We’re interested in making the little fingers at the tip of an elephant arm,” says Desai, professor in the Wallace H. Coulter Department of Biomedical Engineering (a joint department of Georgia Tech and Emory University), associate director of the Institute for Robotics and Intelligent Machines (IRIM) leading the medical robotics and human augmentation area, and a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

Those little fingers are kind of the reason Desai came to Atlanta last year from the University of Maryland. They’re part of the impetus that led to creation of the Georgia Center for Medical Robotics (GCMR), the multidisciplinary research initiative being launched at Georgia Tech.

“Really, this is a vision I’ve had for a very long time, to develop a center in the area of medical robotics,” explains Desai, founding director of the GCMR. “It’s one of the primary reasons I came to Georgia Tech.”

He was particularly lured by the prospect of collaborating with the Emory and Morehouse schools of medicine, and Children’s Healthcare of Atlanta.

“The question I ask myself is, ‘how can we make an impact in different areas of medical robotics,’ and the answer is, you bring together a combination of excellent engineering and top notch medicine,” says Desai, who has been pleasantly floored by the feedback and interest among clinicians like Josh Chern, a pediatric neurosurgeon at Children’s Healthcare of Atlanta.

“A surgeon’s ability to see and to physically manipulate tissues are two of the basic tenets of surgery,” says Chern. “I believe surgical robotics will be an important next step to improve the precision and accuracy of surgical manipulations.”

Using engineering principles to solve medical problems is a burgeoning field that will keep growing, offering patients more options, notes David Stephens, interim dean at the Emory School of Medicine.

“Traditional drug therapy and diagnostics will continue to develop and improve, but new technological applications and innovative approaches will be critical in improving outcomes and increasing efficiencies in health care delivery,” Stephens says.

Meanwhile, Desai’s lab is already working on robots that can take a surgeon like Chern outside his line of sight – machines that can be lowered into the brain and sweep side to side, or rotate 360 degrees, offering previously impossible vantage points.

Chern also points to trends in healthcare delivery that have “focused on efficiency, minimizing errors and waste, and minimizing patient discomfort, to name a few.” He and fellow GCMR stakeholders see the research center as a pathway to further improvements in the safety and quality of care.

“With a desire to curb health care costs but also provide improved care, the application of robotics for precision surgery and in rehabilitation is very promising,” notes Steve Cross, Georgia Tech Executive Vice President for Research. “Georgia Tech, with its large array of regional health care organizations and the industry base, make this the perfect place to do leading edge research, co-innovate with health care professionals, and accelerate translations of research into medical use.”

Team Approach

Desai has invited a wide-range of experts into the fold, and is thinking beyond robotics, strictly speaking. You may not be working on robots, but perhaps, for example, you’ve developed imaging processing technology that could be applied to one of these machines. The point is, Desai and his colleagues are encouraging the questions and the conversation, and identifying needs in the delivery of care – needs that change quickly.

“Healthcare is undergoing a time of rapid change in terms of human augmentation, automation, and quality control of diagnostic processes,” notes Carolyn Meltzer, GCMR advisory board member and associate dean for research at Emory University School of Medicine, where she chairs the Department of Radiology and Imaging Services.

One of the center’s distinguishing characteristics, Desai says, is its focus on pediatric as well as adult patients. He’s developing patient-specific devices, utilizing 3D printing technology to create tailor-made medical robots.

“We’re trying to develop very small, miniature technologies that are, by comparison, much smaller than existing devices in the marketplace,” says Desai.

In addition to building new bridges between multiple disciplines (with more than 40 faculty researchers already, all of them aimed toward developing better medical robotic devices), the center also helps the Coulter Department further its two-headed mission of creating academic as well as research opportunities.

Susan Margulies, chair of the Coulter Department, calls the GCMR, “an exciting, timely initiative in biomedical engineering at the intersection of engineering, computing sciences, medicine, and health that will offer educational, training, and research opportunities for faculty and students. The Coulter Department has a rich history of excellence in transformational research and in translating biomedical engineering research to improve quality of life, and the GCMR will be one of our signature programs.”

The development and growth of GCMR also helps solidify Atlanta’s reputation as a hub for medical robotics research. With a long-established culture of collaboration between different institutions, the city is a natural location for this kind of endeavor, according to Stephens, who points to some of the region’s proven benefits: the highly-ranked Coulter Department; an existing partnership between Tech, Emory, and the Morehouse School of Medicine in the NIH-funded Atlanta Clinical and Translational Science Institute; Children’s Healthcare of Atlanta; and the Georgia Research Alliance.

“Atlanta’s well-established academic and health care partnerships will provide a strong foundation,” Stephens assures. “And the center will create even more opportunities for shared initiatives.”

Desai, who heads up the RoboMed lab in the Coulter Department, may be the first faculty member at Georgia Tech to be fully engaged in the area of surgical robots, but he doesn’t expect to be lonely. In fact, he’s already working on bringing the world to Atlanta, creating the International Symposium on Medical Robotics, which debuts next year.

Some of the world’s top researchers from academia and industry will come together March 1-3, 2018, at the historic Academy of Medicine, to exchange ideas and foster future developments in the field. And the symposium should also serve as a fitting grand-opening for Georgia Tech’s newest research center.

“We want the Georgia Center for Medical Robotics to become a sustainable central hub of research and thought leadership,” says Desai. “So we’re making ourselves visible to the outside world.”

LINKS:

Georgia Center for Medical Robotics

International Symposium for Medical Robotics

Robomed Lab

Creating the Next in Robotics

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

Overall, the news from the study is good. Evolution appears, through the ages, to have weeded out genetic influences that promote disease, while promulgating influences that protect from disease. But there's also a hint of bad news for us modern folks. That generally healthy trend might have reversed in the last 500 to 1,000 years. 

So, who appears to have had the healthier genes? The “cavemen?” We moderns? And who was more genetically susceptible to mental illness?

READ about our genomic health heritage here, and meet our Copper Age ancestor, the “Iceman.”

The QBioS Ph.D. was established in 2015 and includes more than 50 program faculty. The mission of QBIoS is to educate students and advance research, enabling the discovery of scientific principles underlying the dynamics, structure, and function of living systems at scales from molecules to ecosystems.   Of the seven incoming students, four are affiliated with the School of Biological Sciences and three are affiliated with the School of Physics.

Kelimar Diaz Cruz obtained a B.S. in Physics from the University of Puerto Rico, Rio Piedras Campus in Puerto Rico this year, before joining the QBioS Ph.D. “Before my undergrad, I had no idea there were many branches of Physics,” Diaz notes.  “Once I learned Biophysics was one of them I immediately knew in what direction I wanted to head. The QBioS Ph.D. program will allow me to develop interdisciplinary and quantitative approaches for the understanding of biological systems. There is no better program that aligns with my interests. I am looking forward to expanding my knowledge of biological sciences as I work alongside faculty and researchers in different areas.”

Guanlin Li graduated with a B.S in Mathematics and Physics Minor in 2016 from Arizona State University and earned his M.S in Mathematics from Georgia Tech this year before transferring into QBioS. “I like to utilize mathematical and computational tools to answer fundamental questions raised in the biosciences,” Li says. “QBioS opens a new door that brings biosciences to a quantitative side, from experimental interpretations to equations and laws. I'm excited and looking forward to joining this new program.”

Daniel Muratore completed a Bachelor's in Biological Sciences at the University of Chicago in 2016, focusing primarily in theoretical ecology. After graduating, he worked in Maureen Coleman's lab at the University of Chicago on microbial ecology and biogeochemistry for marine and lake systems. Muratore moved from to Atlanta to work with Weitz on virus-host models and nutrient dynamics in marine ecosystems and to start his PhD in QBioS, explains, “I am very excited to use modeling approaches and robust analytical methods to handle a diversity of data coming from the worlds of oceanography, molecular biology, and bioinformatics for the purpose of generating new knowledge about the goings on of the marine microbial ecosystem.”

Brandon Pratt graduated from the University of Washington earlier this year, receiving Bachelor of Science degrees in neurobiology and in molecular, cellular, and developmental biology. He notes, “I was drawn to the PhD program in Quantitative Biosciences at Georgia Tech because of its unique design that bridges the gap between biosciences and engineering. Coming from a primarily biosciences background, this program allows me to expand my repertoire of technical skills and knowledge to include those from the fields of computer science and engineering. I aim to use these skills to better describe living systems, particularly neural systems.” Pratt intends to conduct research involving how sensory information is acquired, processed, and integrated in the nervous system.  

Kai Tong earned his B.S. in Biological Sciences from Fudan University in Shanghai, China, this year. Initially admitted into the Ph.D. program in Biology, Tong decided to transfer to QBioS. “I was amazed by the easy-going and collaborative atmosphere here," Tong says. “And equally importantly, the fit with my research interests in major evolutionary transitions and social evolution.” He noted that his training as a ‘traditional’ biologist involved a leap to transfer to QBioS. “This out-of-comfort-zone effort will allow me not only to use more quantitative toolkits to tackle biological questions, but also to test hypotheses or perform predictions that usual experimental methodology may not be able to, as well formulate insights into a more abstract and generalizable way.”

Akash Vardhan received his training in Production Engineering from Jadavpur University, India, graduating in 2013. After completing his undergraduate education, he worked as a vehicle dynamics test engineer in the automobile industry, before moving on to study the mechanics of bug flight in Sanjay Sane’s lab at the National Centre for Biological Sciences in Bangalore, India. “As a part of the QBioS program I would love to continue working on the biomechanics and control of locomotion in a wide variety of animals,” Vardhan says. “Form and function is another area that I find really fascinating, how seemingly simple interactions can give rise to an emergent behavior which is really complex has also gotten me really interested.”

Mengshi Zhang received her B.S. in Biotechnology from South University of Science and Technology of China in 2015 and then switched to the Department of Physics at the Chinese University of Hong Kong for her master’s degree (MPhil), graduating earlier this year. She is fascinated by the quantitative descriptions of biological phenomena and drawn to this interface in QBioS. Zhang has backgrounds in system biology and synthetic biology, and experience in wet and dry labs. “I would like to combine both computational analysis and experimental methods and look forward to integrating principles of physical, mathematical and biological science together within QBioS,” she says.

“We were testing an intuition,” says Urko Marigorta, lead author of the study, “Transcriptional Risk Scores link GWAS to eQTL and Predict Complications in Crohn’s Disease,” published in the journal Nature Genetics.

“We wanted to see if checking the actual expression of pathogenic genes involved in disease is better than just looking at an individual’s DNA when assessing the risk for disease,” adds Marigorta, a postdoctoral researcher in lab of Greg Gibson, professor in the School of Biological Sciences and a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

This was part of a multicenter research initiative, the Crohn’s & Colitis Foundation’s “RISK Stratification” study (the largest new-onset study of pediatric Crohn’s disease patients), and a follow-up to research published earlier this year in the journal, The Lancet.

That study, says Gibson, evaluated “whether anti-TNF treatment really is beneficial in reducing inflammation and preventing progression to complicated Crohn’s disease. It is, but apparently only for a subset of patients. Our contribution there was to show that this subset can, to some extent, be identified at diagnosis on the basis of their overall gene expression profile in the ileum.”

The Nature Genetics paper takes advantage of the data sets analyzed in the previously published research. The RISK Stratification Study involved 28 clinics and 1,800 pediatric patients – a good sample size, according to Marigorta, who adds, “most important, [we had] two forms of biological data: DNA and gene expression from the small intestine. Importantly, the gene expression from RISK was obtained at diagnosis, when kids went to the hospital and before developing complicated versions of Crohn’s disease.”

So basically, Marigorta and Gibson wanted to test their novel approach, TRS, against genetic risk scores (GRS), or scores based on an individual’s DNA, which is currently the dominant approach in the field. But predicting disease risk from just DNA is difficult.

“In the last few years we’ve learned about many genes that are associated with disease – genes that have mutations, that are more frequent in people with disease than in healthy people,” Marigorta says. “But many people with mutated genes do fine, whereas others without them end up getting sick with some disease. Most of the field is trying to discover more of these mutations, which is totally fine because that will tell us more about biology, and will make for good drug targets. But we’re not sure it will add that much in terms of prediction.”

Marigorta’s statistical and bioinformatics analyses of the genomic data demonstrated that their intuition was on target: gauging the expression of risk genes (TRS) does a better job of predicting complications of Crohn’s than just adding up the number of risk genes (GRS).

“So, instead of trying to predict how good a football team is going to be by adding up how many players make $10 million a year, we actually evaluate how well they are performing,” says Gibson, using a familiar sports analogy.

This paper published in Nature Genetics was a collaboration of 23 author/researchers from 18 institutions – two in Canada and 16 in the U.S., including Emory University’s School of Medicine. Emory physician/professor Subra Kugathasan, director of the Children’s Healthcare of Atlanta Combined Center for Pediatric Inflammatory Bowel Disease, shares senior authorship with Gibson (who was the corresponding author). Key leadership also came from co-authors Lee Denson (Cincinnati Children’s Hospital) and Jeff Hyams (Connecticut Children’s Medical Center)

Going forward, Marigorta sees two primary directions that the TRS research may take.

“We’d like to see if it works for other traits and we have evidence that it does, at least for autoimmune diseases such as juvenile arthritis,” he says. “And more importantly, we’d like to see if it works when using gene expression from blood draws. Imagine, down the road, if you could fine-tune the predictions of risk due to your DNA with information gained from looking at gene expression from a simple blood draw at your once-a-year checkup.”

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

Lu’s project, “Live imaging of the C. elegans connectome,” with Oliver Hobert of Columbia University, entails the development and dissemination of tools that empower the C.elegans neuroscience community to study the connectome of this nematode, which was the first multicellular organism to have its whole genome sequenced.

NSF’s NeuroNex awards bring together researchers across disciplines with new technologies and approaches, with the aim of yielding novel ways to tackle the mysteries of the brain.

“Through the development of advanced instrumentation to observe and model the brain, we're closer to our goal of building a more complete knowledge base about how neural activity produces behavior,” said Jim Olds, NSF assistant director for Biological Sciences.

“NeuroNex seeks to take that progress forward, by creating an ecosystem of new tools, resources, and theories,” Olds added. “Most importantly, NeuroNex aims to ensure their broad dissemination to the neuroscience community. With these awards, NSF is building a foundation for the next generation of research into the brain.”

Lu and Hobert, whose project is one of 17 to receive a NeuroNex award, have been awarded $739,277 for three years, starting September 1.

NeuroNex is part of NSF’s Understanding the Brain program, which is the avenue through which the foundation participates in the national Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, an ambitious alliance formed by the Obama Administration, bringing together federal agencies and other partners to enhance our understanding of the brain.

Headlines, of late, have touted the successes of targeted gene-based cancer therapies, such as immunotherapies, but, unfortunately, also their failures.

Broad inadequacies in a widespread biological concept that affects cancer research could be significantly deflecting the aim of such targeted drugs, according to a new study. A team exploring genetic mechanisms in cancer at the Georgia Institute of Technology has found evidence that a prevailing concept about how cells produce protein molecules, particularly when applied to cancer, could be erroneous as much as two-thirds of the time.

Prior studies by other researchers have also critiqued this concept about the pathway leading from genetic code to proteins, but this new study, led by cancer researcher John McDonald, has employed rare analytical technology to explore it in unparalleled detail. The study also turned up novel evidence for regulating mechanisms that could account for the prevailing concept’s apparent shortcomings.

RNA concept incomplete

The concept stems from common knowledge about the assembly line inside cells that produces protein molecules. It starts with code in DNA, which is transcribed to messenger RNA, then translated into protein molecules, the cell’s building blocks.

That model seems to have left the impression that cellular protein production works analogously to an old-style factory production line: That the amount of a messenger RNA encoded by DNA on the front end translates directly into the amount of a corresponding protein produced on the back end. That idea is at the core of how gene-based cancer drug developers choose their targets.

To put that assumed congruence between RNA production and protein production to the test, the researchers examined -- in ovarian cancer cells donated by a patient -- 4,436 genes, their subsequently transcribed messenger RNA, and the resulting proteins. The assumption, that proverbial factory orders passed down the DNA-RNA line determine in a straightforward manner the amount of a protein being produced, proved incorrect 62 percent of the time.

RNA skews drug cues

“The messenger RNA-protein connection is important because proteins are usually the targets of gene-based cancer therapies,” McDonald said. “And drug developers typically measure messenger RNA levels thinking they will tell them what the protein levels are.” But the significant variations in ratios of messenger RNA to protein that the researchers found make the common method of targeting proteins via RNA seem much less than optimal.

McDonald, Mengnan Zhang and Ronghu Wu published their results on August 15, 2017 in the journal Scientific Reports. The work was funded by the Ovarian Cancer Institute, The Deborah Nash Endowment, Atlanta’s Northside Hospital and the National Science Foundation. The spectrophotometric technology needed to closely identify a high number of proteins is not widespread and is quite costly but is available in Wu’s lab at Georgia Tech.

Whereas many studies look at normal tissue versus cancerous tissue, this new study focused on cancer progression, or metastasis, which is what usually makes cancer deadly. The researchers looked at primary tumor tissue and also metastatic tissue.

Hiding drug targets

“The idea that any change in RNA level in cancerous development flows all the way up to the protein level could be leading to drug targeting errors,” said McDonald, who heads Georgia Tech’s Integrated Cancer Research Center. Drug developers often look for oddly high messenger RNA levels in a cancer then go after what they believe must be the resulting oddly high levels of a corresponding protein.

Taking messenger RNA as a protein level indicator could actually work some of the time. In the McDonald team’s latest experiment, in 38 percent of the cases, the rise of RNA levels in cancerous cells did indeed reflect a comparable rise of protein levels. But in the rest of cases, they did not.

“So, there are going to be many instances where if you’re predicting what to give therapeutically to a patient based on RNA, your prescription could easily be incorrect,” McDonald said. “Drug developers could be aiming at targets that aren’t there and also not shooting for targets that are there.”

RNA muted or magnified

The analogy of a factory producing building materials can help illustrate what goes wrong in a cancerous cell, and also help describe the study’s new insights into protein production. To complete the metaphor: The materials produced are used in the construction of the factory’s own building, that is, the cell’s own structures.

In cancer cells, a mutation makes protein production go awry usually not by deforming proteins but by overproducing them. “A lot of mutations in cancer are mutations in production levels. The proteins are being overexpressed,” said McDonald, who is also a professor in Georgia Tech’s School of Biological Sciences.

A bad factory order can lead to the production of too much of a good material and then force it into the structures of the cell, distorting it. The question is: Where in the production line do bad factory orders appear?

According to the new study, the answer is less straightforward than previously thought.

Micro RNA managing

The orders don’t all appear on the front end of the assembly line with DNA over-transcribing messenger RNA. Additionally, some mutations that do over-transcribe messenger RNA on the front end are tamped down or canceled by regulating mechanisms further down the line, and may never end up boosting protein levels on the back end.

Regulating mechanisms also appear to be making other messenger RNA, transcribed in normal amounts, unexpectedly crank out inordinate levels of proteins.

At the heart of those regulating systems, another RNA called micro RNA may be micromanaging how much, or little, of a protein is actually produced in the end.

“We have evidence that micro RNAs may be responsible for the non-correlation between the proteins and the RNA, and that’s completely novel,” McDonald said. “It’s an emerging area of research.”

Micro RNA, or miRNA, is an extremely short strand of RNA.

No one at fault

McDonald would like to see tissues from more cancer patients undergo similar testing. “Right now, with just one patient, the data is limited, but I also really think it shows that the phenomenon is real,” McDonald said.

“Many past studies have looked at one particular protein and a particular gene, or a particular handful. We looked at more than 4,000,” McDonald said. “What that brings up is that the phenomenon is probably not isolated but instead genome-wide.”

The study’s authors would also like to see currently less accessible, advanced protein detecting technology become more widely available to biomolecular researchers, especially in the field of cancer drug development. “Targeted gene therapy is a good idea, but you need the full knowledge of whether it’s affecting the protein level,” McDonald said.

He pointed out that no one is at fault for the possible incompleteness of commonly held concepts about protein production.

As science progresses, it naturally illuminates new details, and formerly useful ideas need updating. With the existence of new technologies, it may be time to flesh out this particular concept for the sake of cancer research progress.

Also READ: Punching Cancer With RNA Knuckles – with John McDonald

The research was supported by grants from the Ovarian Cancer Institute, The Deborah Nash Endowment Fund, Northside Hospital (Atlanta), and the National Science Foundation (CHE-452 1454501). Cancer tissues from ovary and omental sites were collected from a cancer patient at Northside Hospital with informed consent under Georgia Institute of Technology Institutional Review Board protocols (H14337). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of those agencies.

“Actually, my four weeks here have had a huge impact,” says Martin, one of three cadets from the United States Military Academy (USMA) at West Point to take part in a summer REU (research experience for undergrads) program in the lab of Manu Platt, a researcher with the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

“Before, I wasn’t really considering medical school,” says Martin, a rising sophomore from Connecticut majoring in chemistry, who envisions a career in clinical research. “This experience in Dr. Platt’s lab has convinced me: I do want to pursue being a neurologist, and I love the research aspect.”

All three of the West Point cadets – Martin, Jacob Klamm, Dan Whitfield – in Platt’s lab plan on going to medical school eventually. They’ll have their work cut out for them, because the USMA’s medical school program is very competitive – only 10 to 20 members of each class may proceed directly to medical school following graduation. But Platt isn’t going to bet against them.

“These are disciplined, motivated students, and I’m thinking how great it would be to have them here for grad school when the time comes,” says Platt, director of diversity for the National Science Foundation (NSF) Center on Emergent Behavior of Integrated Cellular Systems (EBICS) at Georgia Tech, which facilitated the students’ summer REU experience (as part of Tech’s larger initiative, SURE, for Summer Undergraduate Research in Engineering/Sciences).

EBICS aims to create a scientific discipline for building living multi-cellular machines to address problems in health, security, and the environment. To get there, the program relies on integrated research and education efforts, human resource development, diversity and outreach programs, and knowledge transfer activities.

In addition to Georgia Tech, participating institutions include Morehouse College and the University of Georgia, in addition to the Massachusetts Institute of Technology, University of Illinois at Urbana-Champaign, City College of New York, Morehouse College, University of California-Merced, Boston University, Gladstone Institutes, Princeton University, and Tufts University.

The USMA cadets, who completed their stint at Georgia Tech last week, were sold on the research experience during a visit by Platt to the military academy earlier this year.

“A friend of mine – we were postdocs together – is a professor at West Point, and he invited me to give a talk there,” says Platt, associate professor in the Wallace H. Coulter Department of Biomedical Engineering. “These students have a limited time frame, only a month. But they are amazing students. Going forward, I’d like to grow that pipeline.”

Whitfield, a rising junior majoring in life sciences, had previous research experience at West Point, but wanted a summer program to develop skills and methods for his own research.

“At West Point, we’re doing work on Acinetobacter baumannii, a multi-drug resistant bacteria causing a lot of trouble for soldiers who served in Iraq and Afghanistan,” says Whitfield, who is from Eagle, Idaho.

Klamm, from Enid, Oklahoma, is a rising senior life sciences major who says he’d always been more clinically oriented, but gained a greater appreciation for research while working in Platt’s lab, where the mission is to fuse engineering, cell biology, and physiology to understand how cells sense, respond, and remodel their mechanical and biochemical environments for repair and regeneration in health and disease – and then to translate the results to address global health disparities.

“This was my first real research experience,” Klamm says. “I wasn’t sure what to expect, or how I’d feel about spending eight or nine hours a day in a lab. But it was really cool. I enjoyed it, and I’m definitely more open now to the idea of doing research.”

Genetic therapies, such as those made from DNA or RNA, are difficult to deliver into the right cells in the body. For the past 20 years, scientists have been developing nanoparticles made from a broad range of materials and adding compounds such as cholesterol to help carry these therapeutic agents into cells. But the nano­particle carriers must undergo time-consuming testing — first in cell culture, then in animals. With millions of possible formulas, identifying the optimal nanoparticle to target each organ has been challenging.

Using DNA strands just 58 nucleotides long, researchers from Georgia Tech, the University of Florida, and the Massachusetts Institute of Technology (MIT) have developed a new evaluation technique that skips the cell culture testing altogether — and could allow hundreds of different types of nanoparticles to be tested simultaneously in just a handful of animals.

Read the entire story in Research Horizons.

At Georgia Tech, you’ll find world-class faculty and their star pupils who are helping to redefine the traditional teacher-student relationship. They’re working together on undergraduate research projects, collaborating on papers and presentations, even testing and perfecting new models of learning.

Take Petit Institute researcher Flavio Fenton and recent alumnus Tim Farmer, for example. Fenton directs the CHAOS (Complex Heart Arrhythmias and other Oscillating Systems) Lab. Farmer is a Navy veteran who joined the Fenton lab because he wanted to make an impact in the world.

Fenton and Farmer are featured in the Georgia Tech Alumni Magazine, where you’ll meet six Georgia Tech faculty members and their extraordinary students.

You can read all about it right here.

The research, entitled “Machine Learning Approach to Breast Cancer Localization,” was authored by Park, in the third year of his Ph.D. studies, and Desai, professor in the Wallace H. Coulter Department of Biomedical Engineering.

“In this paper, a feasible way of breast cancer localization at the micro-scale using tissue indentation and machine learning is presented,” explains Park, whose hometown is Daejeon, South Korea, where he completed his undergraduate and master’s degrees in mechanical engineering at the Korea Advanced Institute of Science and Technology. “This approach consists of two main parts, namely, obtaining mechanical signatures of breast tissue through micro-indentation and applying machine learning algorithms to the experimental data for cancer diagnosis.”

The worldwide prevalence of breast cancer was the main inspiration behind Park’s research.

“Breast cancer is the most common type of cancer among women and early diagnosis is a key factor for increasing survival rates and improving patients’ quality of life,” he says.

In Desai’s lab, researchers have found several biomarkers of breast cancer, “such as mechanical, electrical, and thermal properties of breast tissue,” says Park.

“We have been inspired machine learning, which is a powerful tool for data analysis and classification to utilize those biomarkers more effectively in breast cancer diagnosis,” he adds. “We are now moving forward to automate the breast cancer diagnostic process by combining micro-scale characterization with machine learning.”

But LDLs also help serve a number of beneficial and necessary roles, including synthesizing Vitamin D in the skin from sunlight exposure, and aiding in the communication of neurons. The main function of LDLs involves the transportation of cholesterol from the liver to other tissues, to facilitate the formation of cell membranes.

These mobile little particles also taxi triglycerides, phospholipids, antioxidants, fat soluble vitamins, and proteins. And LDLs, which home-in on LDL receptors in cells, may be the perfect vehicle for another, potentially life-saving payload: In a number of studies, they’ve shown promise as nanocarriers for the precision deployment of cancer drugs.

“Since most normal cells do not express as many LDL receptors as tumor cells do, LDLs can be considered a good candidate for targeted drug delivery,” notes Chunlei Zhu, the lead author of a recently-published research paper in Angewandte Chemie (a peer-reviewed journal of the German Chemical Society).

Zhu was a postdoctoral researcher in the lab of Younan Xia, professor in the Wallace H. Coulter Department of Biomedical Engineering and researcher in the Petit Institute for Bioengineering and Bioscience who supervised the research and co-authored the paper, “Reconstitution of Low-Density Lipoproteins with Fatty Acids for the Targeted Delivery of Drugs into Cancer Cells.”

While this isn’t the first study to demonstrate the potential of reconstituted LDLs for targeted drug delivery, the contribution from Xia’s lab lies in the development of a new class of promising biomaterials in the form of naturally occurring fatty acids, which enable drug loading and release.

One way to introduce a therapeutic payload is encapsulation in the hydrophobic core of LDLs, which seems well-suited to drug delivery because of the simple procedure and relatively large loading capacity. Basically, it’s like redesigning and rebuilding the interior of a custom delivery van for better performance, at the molecular level.

The conventional encapsulation process involves use of a nonpolar organic solvent (heptane) to extract the hydrophobic lipids from the core, which is then refilled with a mixture of cholesterol esters and drugs, or cholesterol-drug conjugates.

“However, the presence of excess cholesterol in the bloodstream greatly increases the risk of forming atherosclerosis plaques in the aortic vasculature,” notes Zhu, who has returned to China to take a university faculty position.

In the study from Xia’s lab, researchers replaced the endogenous core lipids with a mixture of lauric and stearic acids, which serve as a matrix for drug loading, and provide several advantages: First, they’re naturally occurring biomolecules, so they serve as biocompatible and biodegradable hydrophobic environment for hydrophobic drugs. Fatty acids also are an important fuel source that may enable metabolism-triggered drug release. They can protect the drug payloads from hydrolysis. And there’s an added bonus: lauric acid has a favorable effect on the increase of “good cholesterol” (high-density lipoprotein, or HDL), and stearic acid enables the decrease of “bad cholesterol,” or LDL, in the bloodstream.

“As such,” the authors write, “these naturally occurring compounds can be considered safe materials for the substitution of cholesterol ester in LDL reconstitution.”

In addition to Zhu and Xia, contributing authors include Petit Institute researcher Krish Roy (professor in the Coulter Department and director of the Marcus Center for Cell-Therapy Characterization and Manufacturing), Pallab Pradhan (research scientist in Roy’s lab), Da Huo and Jiajia Xue (postdoctoral fellows in Xia’s lab), and Song Shen (associate professor at Jiangsu University in China and a visiting scholar in Xia’s lab).

The research road ahead feels endless, many neuroscientists say, and comprehending how the brain generates the human psyche may be decades beyond the horizon. But neuroscience is in a forward lunge powered by sweeping national funding programs such as the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies), which is tapping into the brain to understand it and support well-being.

You can find the Research Horizons feature story here.

Among people who make it to age 85, some 50 percent will have Alzheimer’s, which afflicts slightly more women than men. Consequently, most everyone knows someone who is suffering or has died from the disease.

Late last year, U.S. research on Alzheimer’s received a significant boost in funding. And recently — aided by new tools — scientists, doctors, and engineers around the world have been making fascinating inroads, including at the Georgia Institute of Technology, which collaborates with Emory University’s highly regarded Alzheimer’s research center.

Some of their insights include: Alzheimer’s may work much like mad cow disease. It also may have aspects of inflammatory disease. And a special light has caused immune cells in the brains of mice to clean up bad proteins that are a hallmark of Alzheimer’s.

Read the whole story and watch the video from Research Horizons here.

Steve Cross, Georgia Tech’s executive vice president for research, was one of 11 panelists for Wednesday’s roundtable discussion about “The State of American Science.” The event, organized by the Association of American Universities and The Science Coalition, covered funding, university research and related public policy issues.

“Scientific and technological discovery has been the driving force of American innovation for more than a century, and has resulted in critical advancements in public health, economic growth and national security,” Cross said. “Many of those breakthroughs were realized in the laboratories of the country’s best research universities and made possible because of federal investment and industry collaboration.”  

In 2016, Georgia Tech conducted $791 million in research. The Institute also helped launch more than 100 new startups last year. During the 2016 fiscal year, Georgia Tech received 72 patents and 657 industry contracts.

“Georgia Tech is proud to participate with our peer institutions in this discussion, and we believe it is imperative our institution and others continue the valuable research happening on our respective campuses,” Cross said.

The other panelists included senior research officers from: Florida State University, Iowa State University, Johns Hopkins University, Marquette University, Purdue University, State University of New York, University of California – San Francisco, University of Chicago, University of Missouri – Columbia and University of Rochester.

Several reporters attended the event, including representatives from Science, Bloomberg, Reuters, The Washington Post, Inside Higher Ed and The Chronicle of Higher Education.

The panelists told reporters how universities help fuel the country’s innovation ecosystem. They explained the role of science in policy making and the role of scientists as advocates. They also discussed the impact of proposed cuts to research funding and policies that affect where and how people conduct research.

The panel, held at the National Press Club in Washington, D.C. afternoon, was moderated by Jeffrey Selingo, a visiting scholar at Tech’s Center for 21^st Century Universities.

Since the new degree program was approved by the Board of Regents on Valentine’s Day 2017, nearly 200 students clamored to sign on.

This enthusiastic response was surprising — but then again, not, says Tim Cope, chair of the Undergraduate Neuroscience Curriculum Committee and professor in the School of Biological Sciences and the Wallace H. Coulter Department of Biomedical Engineering.

“Hardly a day goes by that there’s not something in the news — a health concern or a recent breakthrough or societal challenge — that doesn’t involve neuroscience,” he says. “It’s a growing field with so many opportunities, and it’s inspired a lot of interest from our students.”

One of them is Yeseul Heo.

“I got really excited when I learned about the new major,” the rising second-year student says. “I think I was one of the first to turn in my paper to switch.”

Heo’s original major was psychology — and she is keeping that as a minor, along with a double major in international affairs — but she sees neuroscience as a way to put her studies on a more quantitative footing.

“Along with psychology, I wanted to focus more on hard research, specifically on brain activity, and working with quantitative data,” she says.

Heo has gotten a taste of neuroscience already as a student assistant in the lab of Associate Professor of Psychology Eric Schumacher, whose research uses functional magnetic resonance imaging (fMRI) and other experimental techniques to investigate the neural mechanisms for vision, attention, memory, learning, and cognitive control.

A Research Community

Schumacher is one of more than 50 faculty members from disciplines across Georgia Tech who are involved in neuroscience research — and have been for years. But however collaborative, widespread, and even world-renowned these neuroscience efforts have been, what they have lacked, Cope suggests, is “community.”

He and many others anticipate this new undergraduate degree will build that necessary component, for both faculty and students. “It’s a very important, symbolic event in the development of neuroscience on this campus,” he says.

Neuroscience is “the perfect incarnation of an interdisciplinary subject,” says College of Sciences Dean and Sutherland Chair Paul M. Goldbart. 

“It’s also a subject of deep intellectual interest. Who couldn't be curious about how the brain and nervous systems work at the most basic level?”

Goldbart “couldn’t be more excited” about the new degree, because “It opens up a marvelous new channel to a wide variety of career paths and will make Georgia Tech even more appealing to prospective undergraduates in the sciences.”

“I am grateful to everyone who worked so hard to create a program that defines 21^st-century neuroscience education for a 21^st-century technological research university.” 

NeuroX Factor

Getting from neuroscience activity to neuroscience community at Georgia Tech has been something of a journey, starting with the formation of a “NeuroX” committee back in 2014 and ending with Board of Regents approval for the new undergraduate degree in February 2017.

To reach this place, certain boxes had to be checked. It was not enough that faculty were engaged in neuroscience and students wanted it, although that was clearly the case.

Every time the Institute offered a neuroscience course, it maxed out, and professors were constantly asked if there would be more courses, or if they could open up another section.

Still, Cope points out, “It’s a legitimate thing for the administration to think about these things exceedingly carefully. No university can be everything — there’s a limit to resources and we have to be strategic with our planning.”

Basically, the key questions were: Is there a demand for this major from employers? Is there a demand for this degree from students? How would a neuroscience degree program advance Georgia Tech’s strategic plan? And would the program be redundant within the University System of Georgia?

This last question sent Cope over to Georgia State University — the only other USG school with an undergraduate neuroscience degree — to meet with the leadership of their Neuroscience Institute.

“I said, ‘Here’s what we’re planning to do,’” Cope recalls.

“They said, ‘Oh, this is fantastic, with Georgia Tech’s traditions and resources, you bring something unique to the table,’ and they wrote a letter for me right on the spot — they endorsed our plan 100 percent.”

'Kind of Pulsing'

While every neuroscience program has its “multiplication tables,” as Cope terms them — certain facts every neuroscientist has to know — the bigger challenge is, where do students take it from there?

Heo eventually wants to take her neuroscience focus into the study of first impressions. “You develop this first impression within two seconds in your brain, and you don’t control that, ever,” she says.

“So, I want to figure what’s the reason behind it, and if we learn the reason, is there a way to, not eliminate it, but maybe try to understand each other better, avoid racism and discrimination, and bring about more peace.”

As a neuroscience undergraduate, Heo will learn what Cope calls “the three flavors of neuroscience” — cell and molecular, behavioral, and systems.

Beyond these basics, Heo can branch out into one of 10 different specializations — biochemistry, biology, chemistry, computer science, engineering, health and medical, physics, physiology, or psychology.

In her case, completing the psychology specialization will qualify her for a minor in that field.

Students are coming into the program from disciplines all over campus, and all these areas can and do intersect with neuroscience, notes Cope. “To have a degree in neuroscience means you have to be conversant in wide-ranging concepts,” he says.

“In my mind’s eye, I have the sense of neuroscience kind of pulsing — it borrows concepts and technologies from all the fields, but it doesn’t only take, it gives back.”

The undergraduate neuroscience degree will — as with all Georgia Tech disciplines — culminate in a senior research or capstone project.

“We want to leave our students with an experience that really gets their creative juices going and gives them a tantalizing view of what they might do next,” Cope says.

The program website lists 50 occupations for which neuroscience can serve as preparation or grad school foundation, and then, of course, there’s entrepreneurship.

Among the many other student startup and business incubators in and around Georgia Tech, there’s even one called NeuroLaunch, which introduces itself as “the world’s first neuroscience startup accelerator.”

Proving It

Georgia Tech’s Bachelor of Science in Neuroscience launched this fall.

As the community builds and the degree program gains visibility, Cope expects Georgia Tech to carve its niche among neuroscience programs as only Georgia Tech can.

“We’re especially mindful of active learning here, of inquiry-based education, where the students are led to discovery, not just have the discovery dumped in their laps,” he says.

“What we’d like to bring to neuroscience is the strong analytical, deep understanding of concepts and methods that Tech brings to its curriculum in all fields.”

Down the road, Cope sees the undergraduate degree program leading to more and bigger grants for neuroscience research at Tech, and ultimately a Ph.D. program.

In the meantime, he says, there’s much to learn and do, quoting a fortune cookie slip he’s kept in his wallet for more than 25 years now: “It says, ‘You are respectable, you are intelligent, you are creative — prove it.’

I think that applies here. We’ve got a lot of what we need to do some really great things in neuroscience. Now we’ve got to prove it.”

Neuroscience Research in the College of Sciences

Neuroscience is “the perfect incarnation of an interdisciplinary subject,” says College of Sciences Dean and Sutherland Chair Paul M. Goldbart. “It’s also a subject of deep intellectual interest. Who couldn’t be curious about how the brain and nervous systems work at the most basic level?”

Neuroscience majors interested in research have a broad array of options. Researchers at Tech seek to understand the mechanics of brain function and the emergence of normal, aberrant, or developmental behavior from the components of the nervous system at multiple scales of complexity.

The details of every faculty member’s research are diverse, but they all aim to address one or more of the following overarching questions:

1. How does the brain perceive the world, learn new information, express emotions, and produce behaviors?
2. How does the nervous system cooperate with the body it lives in?
3. How does the brain compute responses and commands?
4. How do behaviors emerge from molecules, cells, and systems?
5. How can genetic and environmental factors impact neural functions?

Here are examples of research led by College of Sciences faculty members.

The Reorganization Problem of Neurons: Addressing the neurotoxicity of chemotherapy

By A. Maureen Rouhi

Even as a child, Tim Cope was fascinated by how physically disabled people move. Why can’t they move normally? That fascination led to scientific curiosity about why it can be so difficult to recover normal movement after disease or damage.

One path of inquiry Cope has pursued is the organization of sensory signals to the spinal cord. Over more than two decades of research, he and others have shown that sensory signals can be restored to normal when damaged sensory nerves regenerate and reconnect with muscle; however, their connections in the central nervous system reorganize.  

Central reorganization changes the flow of sensory information, so some neurons completely lose sensory signals, while others receive twice as much input. Thus, regeneration is not synonymous to recovery, says Cope, a professor in the School of Biological Sciences and in the Wallace H. Coulter Department of Biomedical Engineering and member of the Parker H. Petit Institute for Bioengineering and Bioscience (IBB).

Another condition that may cause peripheral nerve damage, and subsequent reorganization is chemotherapy. “We have peripheral nerve regeneration after chemo, but we don’t regain normal function,” Cope says. “Maybe it’s this reorganization problem again.”

To explore this possibility, researchers in Cope’s lab recorded sensory signals of rats after chemotherapy. In this case, the sensory signal itself showed long-lasting abnormality. However, they also found that even when nerves are not structurally damaged by chemotherapy, the sensory signal remains atypical.

These puzzling findings led to the discovery that chemotherapy affects cellular mechanisms responsible for translating mechanical stimuli — for example, muscle stretch — into sensory signals. As with peripheral nerve trauma, sensory information changes, but for a very different reason. 

Cope relishes this unexpected turn of the research. “Our chemo studies led us to a way of restoring the signals to normal, and I think our findings may have some translation to humans,” he says. “We believe if we can fix the signal, then we can improve the daily movement activity in patients who otherwise might experience disability long after chemotherapy is discontinued.”

Fixing the signal means restoring the damaged proteins, or just bypassing them. Cope’s team has identified a drug to do the latter. “But a better solution is to find out exactly what protein is damaged and restore it through genetic therapy or other molecular techniques.”

Next, Cope hopes to do genetic screening to try to get a comprehensive list of the proteins damaged by chemotherapeutic neurotoxicity, particularly those involved in generating sensory signals. This work would be in collaboration with John McDonald, a cancer expert, professor in the School of Biological Sciences and member of IBB.

Meanwhile, other work goes on in the Cope lab. “If you’re interested in how we generate movement and how sensory information is required to generate that movement, and what goes wrong in various disease and damage situations, then whether you’re a chemist, an engineer, or interested in behavioral science, there is an entry level for you in my lab to study those things,” he says.

Memory, Emotion, and Aging: Exploring “memory clutter” and the neuroscience of human cognition

By Renay San Miguel

Forget where you parked your car? Misplaced your keys? Can’t remember what a restaurant dinner companion just said to you? All signs of early-onset dementia, right?

Not quite, says Audrey Duarte, associate professor in the School of Psychology and principal investigator in Georgia Tech’s Memory and Aging Lab. “There are memory changes we think of as being associated with dementia, and that’s very concerning, but that’s not really what we’re talking about,” Duarte says. “Just by getting older, we experience more memory impairment.”

Take that restaurant dinner, for example. When you’re younger, people coming in and out of the dining room, nearby conversations, and any other distractions are easier to tune out. “As we get older and we have that impaired ability to ignore distracting information, it gets incorporated into our memories,” Duarte says. “That information is there even at the subconscious level, and that creates what we call memory clutter.”

That clutter gums up the brain and forces older adults to work harder than before to recreate that restaurant experience in their minds in the hopes of remembering information.

Duarte’s 2016 study on memory clutter is the latest example of her focus on human cognition. How does the brain process new information, and how is that tied to emotions and behaviors?

“I’m a memory person, so I always think memory is the most important thing,” she says. The information we take into our brains has to be processed by our sensory systems — what we see, hear, etc. — and then filtered through our past experiences. “Those memories have emotional associations with them, some positive, some negative. If it comes down to why a particular emotion is stronger than others, we don’t really understand why the brain is organized that way.”

Duarte’s research involves exploring which areas of the brain are necessary for emotional processing. She and her team in the Memory and Aging Lab use electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to determine which parts of the brain make those connections between memory and emotion.

It’s known that the amygdala, located within the brain’s medial temporal lobes, is associated with processing emotions. Duarte says her research shows that “if you see something that’s negative, the amygdala is sensitive to that.” But she emphasizes that other brain regions also seem to process stimuli associated with bad emotions such as disgust, sadness, anger, etc.

Duarte is determined to discover how disease, injury and aging effect all aspects of human cognition. She believes the future of her field will bring an interdisciplinary focus, folding in computational modeling, biology, genetics and biomedical engineering.

The research tools she’s using now are noninvasive. “We’re not implanting electrodes in people.” But to get a complete picture of neural communications — how that supports human cognition and what happens when that communication breaks down — “we’re going to have to drill down to the neuron level itself.”

Protective Responses: Neurons linked to itch and bronchoconstriction

By A. Maureen Rouhi

Itch. Just seeing the word makes you feel itchy. The sensation that makes you want to scratch your skin does the same to other mammals, amphibians, reptiles and birds. “Itch sensation is an evolutionarily conserved way used by many animals to sense environmental irritations and respond accordingly,” says Liang Han, an assistant professor in the School of Biological Sciences. 

Han’s laboratory strives to understand how the nervous system receives, transmits, and interprets stimuli to induce responses. In particular, she is interested in the mechanisms of nocifensive — or protective — responses. She wants to know how alterations in neural pathways that mediate these responses lead to chronic disease. For now, she’s focusing on two protective responses: itch and constriction of the lungs’ airways, or bronchoconstriction.

“Everyone experiences itchy feelings — when they get a mosquito bite or are wearing a prickly wool sweater.” Han says. In these cases, the itch is relieved by scratching. But imagine if the itchiness goes on and on!

“Chronic itch accompanying disease can be devastating,” Han says. More than 40 percent of patients receiving dialysis for end-stage renal disease suffer from severe itching, as do 60 to 70 percent of patients with advanced liver disease, according to Han. Persistent itching can lead to sleep deprivation and depression. Despite the clinical importance of itch sensation, Han says, the mechanisms governing it are largely unknown.

A long-standing question is whether itch-sensing neurons are itch specific or also signal other sensations such as pain. In earlier work using molecular genetic approaches, Han discovered a subpopulation of sensory neurons specifically linked to itch sensation. When those neurons are removed from experimental mice, the animals do not sense itch from multiple stimuli, but they continue to sense pain or pressure. Conversely, when these neurons are activated by painful stimuli, they elicit itch, not pain. “The data demonstrate the existence of the dedicated itch-sensing neurons,” Han says, “and advances our understanding of the cellular mechanisms of itch sensation.”

Now at Georgia Tech, Han aims to discover the mechanisms of chronic itch and find therapeutic targets for treatment, while also advancing understanding of bronchoconstriction.

The lungs’ sensory nerves help regulate the respiratory system, for example, by controlling breathing patterns and evoking airway-protective behavior such as coughing, airway constriction, and mucus secretion. Han’s lab recently discovered a subpopulation of sensory neurons that, when stimulated, induce bronchoconstriction and airway hyperresponsiveness, both of which are hallmarks of asthma.

“Current investigations of the pathogenesis of asthma have largely focused on immune responses,” Han says. “However, anti-inflammatory treatment only partially controls asthma symptoms. We need to understand the involvement of non-immune systems in the disease.”

Recent studies, including Han’s, indicate an important role for the nervous system in the pathogenesis of asthma. “We are currently using molecular genetic tools to investigate whether blocking those neurons can inhibit asthma in a mouse model,” she says. “We hope to obtain insights into the neural mechanisms of asthma and identify neuronal targets for management of asthma symptoms.”

Muscle-Neuron Connections: Maintaining contact as aging occurs

By A. Maureen Rouhi

Young C. Jang aspires to understand the aging process, particularly as it relates to muscle loss. An assistant professor in the School of Biological Sciences and the Wallace H. Coulter Department of Biomedical Engineering, and member of the Parker H. Petit Institute for Bioengineering and Bioscience, Jang hopes that therapeutic interventions could be developed to treat muscle loss, whether from aging or disease.

In considering scientific questions, Jang’s approach is to look at the forest. “You can be interested in muscle,” he says, “but you can’t just work on muscle to understand the whole biological process.”

Motor neurons connect muscles to the nervous system; however, the muscle-neuron connection can be severed by injury or disease. When the muscle is restored to function, the junction can be reconnected.

With age, the reconnection between muscle and neuron becomes increasingly difficult. When contact disappears, Jang explains, “muscles cannot communicate with the spinal cord and brain, and they start to degenerate.” Jang studies how to keep these connections going in hopes of developing ways to prevent or treat muscle loss. 

Aging and disease have some common pathways, Jang says. One is oxidative stress. When the body has an excess of reactive, oxidizable species, aging occurs faster than usual.

Jang’s work has shown that oxidative stress contributes to disconnection of the muscle-neuron junction. Oxidative stress is a well-accepted theory of aging, Jang says. It posits that when the body’s balance of antioxidant enzyme and oxidizing free radicals tilts in favor of free radicals, aging accelerates.

Jang’s early work showed that, in mice, removing the antioxidant enzyme — which increases reactive oxygen species — promotes severance of the muscle-neuron junction. In humans, Jang notes, genetic mutation of the same enzyme leads to amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, a motor neuron disease.

“We’ve found one mechanism that promotes detachment,” Jang says. “Can we reverse the process or slow it down?” Looking for ways to halt or reverse muscle-neuron detachment has taken Jang to multiple paths of inquiry, including caloric restriction, parabiosis, and organs-on-a-chip.

Jang’s caloric restriction research showed that mice receiving only 60 percent of the normal caloric requirement form fewer reactive oxygen species, and the treatment promotes muscle-neuron attachment. Furthermore, caloric restriction rejuvenates muscle stem cells, which help restore the function of muscles degenerated by aging or disease. With aging, these stem cells’ number and viability diminish, thus making muscle more prone to damage, a trend that slows with caloric restriction. 

In physiological research, parabiosis is the physical joining of two individuals. Jang turned to this approach because blood is a way for cells, tissues, and organs to communicate. When Jang joined a young mouse to an old one so that they share the same circulating blood, he found that the muscle-neuron junction in the old animal is rejuvenated. However, “if you put two old animals together, that junction detaches,” Jang says. “Something in young blood is helping preserve the muscle-neuron junction.”

Indeed, Jang has reported a circulating protein in the blood that seems to be an important factor in connecting the muscle-neuron junction. However, this protein “is not the only one,” Jang says. “We need more research.”

Meanwhile, how could parabiosis be applied to humans? “Obviously, we can’t put two humans together,” Jang says. But it is possible to faithfully mimic parabiosis of organs on microfluidic chips. Jang is collaborating with YongTae (Tony) Kim, an assistant professor in the George W. Woodruff School of Mechanical Engineering, to design organ-on-a-chip systems for parabiosis of human organs.

Sensory Input, Neural Networks, and Locomotion: Creating a new rehabilitation paradigm

By A. Maureen Rouhi

So you think walking across a room is easy, peasy? Think again.

“Walking across the room is one of the most complicated things we do,” says T. Richard Nichols, a professor in the School of Biological Sciences and the Wallace H. Coulter Department of Biomedical Engineering and a member of the Parker H. Petit Institute for Bioengineering and Bioscience. Locomotion is complex, he says, the result of networks of nerve cells communicating, processing information, and integrating myriad sensory signals.

In studying how sensory information from muscles helps regulate movement, Nichols has focused on the Golgi tendon organs (GTOs). These sensory receptors in the muscle tell the central nervous system — which consists of the brain and the spinal cord — the amount of force generated by muscles. The spinal cord then distributes the information to different muscles in the limb. The feedback of muscular forces is thought to help determine how the body responds to obstacles or unexpected circumstances.

So far, what we know about GTOs comes from research on animal subjects. Injury to the spinal cord disrupts communication between the central nervous system and the muscles and causes malfunctioning of the spinal cord’s neural circuits, Nichols says. “Muscle weakness or paralysis can result, as well as loss of balance and stability.”

Working with Dena Howland at the University of Louisville, Nichols has discovered a link between the disruption of the force-regulating system and motor disorders from partial spinal cord injury in animal models. They recently started two projects based on the GTO research.

One project, funded by the National Institutes of Health (NIH), aims to discover how the brain stem controls the GTO-generated neural circuits in the spinal cord to meet the needs of different movement tasks. The other project, funded by the Department of Veterans Affairs, will help define the extent to which malfunction in the force-regulating system contributes to motor dysfunction in partial spinal cord injury. It will also test the efficacy of a potential new treatment for spinal cord injury in humans that would not require special equipment.

The potential new treatment is based on the force-regulating neural networks of cats walking up — or down — hill. Researchers in the Nichols lab have shown that these networks are organized for propulsion when cats walk uphill and for suspension and braking when cats walk downhill.

“It turns out that in spinal cord injury, the downhill pathway becomes extreme” Nichols says. “Animals with spinal cord injury tend to crouch; it’s like an exaggeration of walking downhill.”

Suppose animals with spinal cord injury are rehabilitated by exercising under downhill-walking conditions? The idea is counterintuitive but, Nichols thought, “maybe the central nervous system has some internal wisdom that will say, okay, now we need to repair this injury.” Could training in this particular way promote recovery from partial spinal cord injury?

Nichols and Howland proposed this rehabilitation treatment to Veterans Affairs and received funding. “At the same time, because of our work at Tech, we can find whether the same exercise causes a change in the neural networks of the spinal cord,” Nichols says. Through the NIH grant funding, Howland and Nichols aim to mechanistically connect the recovery with restoration of normal function in the spinal network.

Biomechanics of Locomotion: Toward next-generation artificial limbs

By A. Maureen Rouhi

Research in the lab of Boris I. Prilutsky aims to understand the biomechanics and control of locomotion, which comprises the movements that take two- and four-footed animals from place to place.

During locomotion, sensations from the limbs (called sensory feedback) inform the nervous system about the state of the movement. Prilutsky studies how this sensory feedback affects locomotion. In particular, he investigates feedback from foot pressure and limb motion.

Disrupting the feedback, through injury for example, can lead to instability and falls during locomotion. “We modify sensory pathways in experimental animals and in computational models and observe the effects on locomotion,” says Prilutsky, a professor in the School of Biological Sciences and a member of the Parker H. Petit Institute for Bioengineering and Bioscience.

A key research tool is a neuromechanical model the Prilutsky group developed in collaboration with the group of Ilya A. Rybak, at Drexel University. This model accurately reproduces the walking mechanics and muscle activity of cats. Computational experiments have pinpointed the sensory feedback pathways that produce mild and severe locomotion defects when interrupted. These predictions have been experimentally tested.

In a recent study, for example, Prilutsky’s team injected local anesthetic to the paw pads on one side of a cat to block the sense of touch. Under this condition, the animal loses the symmetry of its gait and becomes less stable. The effect can be reversed, however, by electrically stimulating the nerves that convey the sense of touch to the central nervous system. When that happens, the cat’s walk becomes symmetric and stable again.  

In other experiments, they removed muscle stretch feedback – or stretch reflex – from selected muscles and investigated the effects. “We found that this feedback is task- and muscle-dependent,” Prilutsky says. For example, loss of feedback from certain muscles of the ankle causes problems only in downslope walking. More recently, they found that removing the stretch reflex from hip flexors causes profound changes in locomotion, as predicted and explained by their computational model.

“From our experimental and computational studies, we gain insight into how spinal circuits cooperate with the moving body segments during locomotion,” Prilutsky says.

Those insights are now propelling Prilutsky and others toward prosthetic devices that behave like natural limbs. For example, Prilutsky is applying discoveries about sensory pathways, feedback loops, and natural control signals from the nervous system in the field of osseointegrated — or bone-anchored — limb prostheses. In this approach to attaching prosthetic devices, the artificial limb is directly anchored to the bone through a titanium rod, similar to a dental implant. Potentially this implant can be used as a neural interface between the prosthesis and nerves in the stump.

Although used in Europe, bone-anchored limb prostheses are not approved in the U.S. because of the high rate of skin infections, which develop when skin fails to form a close connection with the bone implant. However, Prilutsky and others have shown that, in rats, use of porous titanium allows skin to grow into the implant, thereby reducing infections. Recently they experimented with cats to test this implant in natural walking conditions to see whether it forms a tight bond with skin and bone and whether and how the animals use a bone-anchored prosthesis for walking. “It works,” Prilutsky says.

Now the stage is set for the next phase: using the implant as a neural interface between the prosthetic device and the nerves in the residual limb so that the nerves and prosthesis talk to each other, and the prosthesis is controlled naturally without the person’s attention. If the promise of this approach is fulfilled, it could revolutionize prosthetics.

Moving in a Complex World: How do insects do it?

By A. Maureen Rouhi

How do animals navigate their environments? That question motivates the research of Simon Sponberg. An assistant professor in the School of Physics with a joint appointment in the School of Biological Sciences, Sponberg studies animals to discover how they move around in a complex world.

“Perceiving and then navigating the irregular terrain of Earth requires sophisticated processing by the brain,” says Sponberg, who received a National Science Foundation Early-Career Award in 2016 in recognition of his promise as a teacher-scholar and is a member of the Parker H. Petit Institute for Bioengineering and Bioscience. “It also demands that the brain work in conjunction with an animal’s body and the environment surrounding it.”

Animals have evolved to negotiate almost every environment on this planet. To do this, Sponberg says, their nervous systems acquire, process, and act upon information. “Yet their brains must operate through the mechanics of the body’s sensors and actuators to both perceive and act upon the environment,” he adds.

In Sponberg’s lab, researchers are studying how muscles operate as soft, living matter. They’re trying to understand the physics of moving animal bodies and the computational principles implemented in the sensors — such as eyes or antennae — of animals in motion.

“Our research investigates how physics and physiology enable animals in motion to achieve the remarkable stability and maneuverability we see in biological systems,” Sponberg says. “We explore how animals fly and run stably even in the face of repeated perturbations, how the multifunctionality of muscles arises from their physiological properties, and how the tiny brains of insects organize and execute movement. We study how the grace and agility of animal movement arises from the synthesis of its parts. Among these is the brain — a crucial part, but not the only one.”

The hawkmoth is a frequent subject of Sponberg’s investigations. The swift-flying insect typically imbibes nectar while hovering over a flower. Feeding usually takes place at dusk, when light is limited. It’s hard enough to see in dim light and even more when it gets dimmer with time. Yet hawkmoths also hover in air while following a flower that’s swaying with the wind. How do they do it?

Sponberg’s group has shown that hawkmoths slow their brain down to improve vision in dim light, much like increasing the exposure on a camera.  However, this adjustment can cause their motion to blur, so they only slow down to the point where they can still track the wind-blown motions of the flowers they prefer in nature. The behavior demonstrates that their neural circuits adapt exquisitely to the environment.

More recent work on three hawkmoth species tracking the group’s “roboflowers” suggests that simple models of neuronal processing can account for interspecies differences in adapting to different light intensities, and the moths actually use touch sensors on their proboscis to help feel the flower’s movements.

“Behavior, especially movement, arises from the context in which the brain acts,” Sponberg says. “We start by asking questions like, “If we know something about the biophysics of how muscles works, how might the brain activate and control muscle to enable an animal to be most agile and versatile?

“What we are finding is that how brains process sensory input and program motor output is intimately coupled to the physics of the surrounding systems and the features of the environment the animal most cares about. Figuring out these coupling principles is a huge task but one that we are confident will help us better understand how we think and act.”

Intent and Action: Unpacking a little-understood aspect of skilled movement

By A. Maureen Rouhi

Lewis A. Wheaton wishes to play golf like a pro. He could raise his game by watching videos of star players like Rory McIlroy. But Wheaton knows from experience — and his research — that observation alone doesn’t always help motor learning.

Research in Wheaton’s lab is explaining why observing people who are highly skilled at motor tasks may not be helpful to those who are far less proficient. Wheaton is interested in unpacking how the brain integrates information to effect motor behavior, particularly highly skilled tasks that involve hands and tools. His findings underscore the importance of intent.

Consider an array of objects on a table: pens, paper, mug, stapler. “You need intent to use things together,” Wheaton says. “If you decide to write a note, you’ll focus attention on the pen and paper.”

That’s obvious, yet some people with certain neurological injuries have trouble understanding what they need to do to write a note. “It’s not automatic that you can string the information together,” Wheaton says. “Part of our work is understanding the relationship between intent and action and how that falls apart in case of neurological injury.”

Using brain-imaging techniques, Wheaton identifies neural signals that capture intent.

Recently he conducted an experiment with people with sound limbs wearing artificial limbs. The participants were asked to learn how to use the prosthetic limbs by watching a video of another prosthetic-device user.

“The norm in prosthetic limb rehabilitation is to let people figure it out themselves, with help from physical therapists,” Wheaton says. “But most physical therapists have two hands. They don’t know what it’s like to be an amputee.”

The study showed that people who watched other prosthetic-device users became more efficient than those who watched people with sound limbs. 

Another tool is eye-tracking, based on the well-known correlation of eye and arm movements. “Particularly in tasks that involve reaching, the eyes precede the hand,” Wheaton says. Can we see intent from what the eyes are doing?

New research suggests that a key to rehabilitation gains might be rooted in visual strategies that capture specific action intent. The eyes see differently when observing different people do the same task, like bringing an object from one side of a barrier to the other side. When watching a person with sound limbs, the prosthetic-device user’s eyes look only at the task itself: The object starts on one side and ends on the other, Wheaton says.

When watching another prosthetic-device user, the subject’s eyes go over the barrier and are paying attention to the shoulders, which power the prosthetic limb. “They are paying attention to the motor intent instead of just the task,” Wheaton says. “Instead of training execution, which we do a lot in rehabilitation, perhaps we should be training intent.”

Back to golf, Wheaton suggests, “Its’ hard to understand the intent of a professional when you are an amateur, until you develop more skill. Instead of watching Rory, take a different approach. You may be more like Joe, who will help you progress to the next step. Then you’ll meet Mary, who’s a bit better than Joe. She’ll take you farther.”

When to Make a Decision: Accumulating and evaluating evidence

By A. Maureen Rouhi

What was your dinner last night? How about the previous night? How about the week before?

Mark E. Wheeler is interested in memories and what happens in the brain that allows us to remember. Part of what he studies is how we make decisions about the accuracy of what we retrieve. “You can’t remember immediately what you had for dinner a week before because you lack information,” he says. “If you think about it a bit more, you may remember. How can you evaluate the accuracy of your memory? What is happening in the brain when we decide whether our memories are accurate or not?”

Memory is difficult to study, however. “People are often not good at describing how they remember,” says Wheeler, a professor in the School of Psychology. “Some retrieved information may not be easy to communicate, people may ignore some memories, or they may be unaware of other memories.”

To get at memory, Wheeler studies perception, which is easier to manipulate and measure. The hope is that understanding how we evaluate evidence in making decisions based on perception can help us understand what happens when retrieving memories.

When viewed from the brain’s perspective, even simple tasks — such as deciding whether an object is green or yellow — consist of a sequence of processing stages, Wheeler says. These stages can be represented by different patterns of brain activity. “If we understand the process as a system,” Wheeler says, “then we can ask: What parts of this system are involved when things break down or don’t function well?” 

Central to Wheeler’s work is the concept of an accumulation-to-boundary mechanism. “In the midst of gathering evidence, you reach some threshold of evidence: Okay, now I’m going to decide,” Wheeler explains. “The idea is that brain activity that is thought to reflect evidence builds up, and when it crosses that threshold, that is the signal that you have enough information to commit to a decision. We don’t understand precisely how that works, which is why we’re studying it, but there’s a lot of data that this happens at the neural level.”

Instead of asking experimental subjects to remember what they had for dinner, Wheeler asks them to lie still while being scanned by a functional MRI (fMRI) machine at the Georgia State University/Georgia Tech Center for Advanced Brain Imaging. Amid the constant beeping of the scanner, participants receive visual stimuli and make decisions about what they see.

Brain activity data reveal how much evidence participants accumulate before they decide. The basis for this approach was developed a decade ago, when Wheeler and others showed that fMRI allows identification of distinct neural processes that work together when people make decisions based on perception.

Currently Wheeler is interested in how aging affects the way decision-making evidence accumulates and how that manifests in brain activity. His recent work, funded by the National Science Foundation and Georgia Tech, examines how noise — anything that degrades information — affects the accumulation of evidence and decision-making as we get older.

“Perception and decision-making,” Wheeler says, “can involve a series of stages, where you take in sensory information, analyze the information, and accumulate evidence, until you can make a decision. Suppose that aging affects the first stage most significantly, but the latter two are fine. You could target interventions more precisely, if you know where the problem lies.”

The experimental approach, Wheeler notes, can apply to other conditions, such as drug addiction or alcoholism. If one can deconstruct how the brain of an alcoholic takes in and processes information, it may be possible to develop better ways to train alcoholics to avoid that first drink.

The annual seed grant program run by the Petit Institute at the Georgia Institute of Technology pairs two researchers from the Petit Institute as co-principal investigators, one based in the College of Engineering, and one based in the College of Sciences.

The teams and their projects are:

• Ed Botchwey (associate professor, Coulter Department of Biomedical Engineering) and Greg Gibson (professor, the School of Biological Sciences) are working on a project entitled “RNA-Seq and Mass Spectrometry Based Lipidomics of Mesenchymal Stem Cells.” Their long-term goal is to develop processes to maintain and enhance the immune modulatory potency of bio-manufactured mesenchymal stem cells (MSCs) based on modulation of sphingolipid (SL) metabolism.

• Frank Hammond III (assistant professor, Coulter Department of Biomedical Engineering) and Gil Weinberg (professor/director of Center for Music Technology) are working on a project entitled, “Ultrasound–Based Recognition of Human Intent for Skillful Control of Dexterous Robotic Prostheses.” Ultimately, they plan to use portable ultrasound and deep learning methods to recognize subtle, complex patterns of change in skeletal muscle morphology (shape changes during muscle contraction and relaxation) and leverage that information to predict human motion intent and enable dexterous, skillful control of feedback-related robotic prostheses.

• Melissa Kemp (associate professor, Coulter Department of Biomedical Engineering) and Facundo Fernandez (professor, School of Chemistry and Biochemistry. Their project is entitled “Metabolic phenotyping in pluripotent systems via MALDI imaging.” They plan to develop novel imaging tools that will have broad applicability to a large variety of biological problems of interest to Petit Institute researchers, including developmental biology, tumorigenesis, and regenerative medicine.

The funding period for each of these grants started July 1, 2017, and the duration will be up to two years, contingent on submission of NIH R21/R01 grant proposal, or an equivalent collaborative grant proposal, within 12 to 24 months of the year-one start date.

This year’s group of grant recipients epitomize the goal of the seed grant program, which is designed to stimulate interdisciplinary research between world-class PIs that haven’t previously worked together.

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

Known as Dry Ion Localization and Locomotion (DRILL), the new device creates a swirling flow that can separate electrospray droplets depending on their size. In this application, one of many potential uses for DRILL, the smaller droplets are directed to enter the mass spectrometer, while the larger ones – which still contain solvent – remain in the vortex flow until the solvent evaporates. Removing the solvent allows analysis of additional ions that may be lost in current techniques and reduces the chemical “noise” that inhibits selectivity of the mass spectrometer.

“A major challenge for detecting small quantities of biomolecules using mass spectrometry technology is that we can’t see everything that is actually in the sample,” said Matthew Torres, an assistant professor in Georgia Tech’s School of Biological Sciences. “The DRILL device provides a new way to solve that problem by increasing the number of ions we can get into the mass spec instrument so we can productively detect them. The ions are there now, but not necessarily in a form that the mass spec can handle.”

Developed by researchers at the Georgia Institute of Technology with support from North Carolina State University, DRILL can be added to existing electrospray ionization mass spectrometers without modifying them. 

“The principle is to make the droplets rotate and use inertia to separate them out by size,” explained Andrei Fedorov, a professor in Georgia Tech’s Woodruff School of Mechanical Engineering. “We want the droplets to stay in the flow long enough to remove the solvent. In practice, smaller droplets remain in the center, where they are can be removed first for analysis, while the larger ones remain on the edge of the flow until they are dried.”

The key idea of DRILL is based on Fedorov’s 2007 invention “Confining/Focusing Vortex Flow Transmission Structure, Mass Spectrometry Systems, and Methods of Transmitting Particles, Droplets, and Ions." (US Patent No. 7,595,487). In the past three years, the DRILL device has been developed with support from the National Institute of General Medical Sciences of the National Institutes of Health, and its latest version was described June 14 in the American Chemical Society journal Analytical Chemistry.

In electrospray ionization (ESI), an electric potential is applied to a solution inside a capillary, producing a strong electric field at the spray capillary tip. That leads to the expulsion of an aerosol containing charged droplets that carry the molecules to be analyzed. The ejected droplets then break up into smaller droplets, creating a plume that expands spatially beyond the inlet intake capacity of the mass spectrometer, resulting in sample loss. The DRILL device provides an effective interface for collection and transmission of charged analytes from ionization sources, such as ESI, to detection devices, such as mass spectrometers, resulting in significantly improved detection capability.

As much as 80 to 90 percent of large biopolymers (proteins, peptides, and DNA) are currently lost to analysis using existing ESI-MS techniques, which have grown in importance to the life sciences community. Capturing all of the biopolymers could lead to new discoveries, said Torres, whose lab studies post-translational changes in proteins. By allowing analysis of large biomolecules, DRILL could facilitate top-down proteomics in which complete protein molecules could be studied without the need to enzymatically break them up into smaller pieces before MS analysis.

“This could allow us to see combinatorial modifications that exist on a single protein molecule,” said Torres. “It’s very important for us to understand how proteins communicate with one another, and DRILL may allow us to do that by more effectively removing the solvent from these types of samples.”

The Georgia Tech researchers are using DRILL in their lab to interface between liquid chromatography and the ESI-MS instrument. Multiple electrodes and inlet/outlet ports enable precise control over the flow generation and guiding electric field inside the DRILL, so the device can be configured for a variety of uses, Fedorov noted. In a general sense, DRILL adds a new approach for manipulating the trajectory of charged droplets, which, when combined with hydrodynamic drag forces and electric field forces, provides a rich range of possible operational modes. 

DRILL can improve the signal-to-noise ratio by a factor of 10 in the detection of angiotensin I, a peptide hormone, and boost the sensitivity for angiotensin II ten-fold to picomole levels. DRILL demonstrated improved signal strength – up to 700-fold – for eight of nine peptides included in a test extract of biological tissue.

DRILL could potentially allow the study of entire cell contents, analyzing thousands of different molecule types simultaneously. That could allow researchers to see how these molecules change over time to detect problems in chemical pathways and to determine why drugs work in some people and not others.

“This could be a huge advance for biologists and others who are interested in protein biochemistry and cell biology because it enhances the sensitivity of the analytical technical and overcomes a major hurdle in studying large biological molecules,” Torres added. “We expect to be able to see things we haven’t been able to see before.”

The Georgia Tech researchers have been collaborating with David Muddiman, a professor in the Department of Chemistry at North Carolina State University, on developing DRILL and its analytical characterization using state-of-the-art mass spectrometry experiments. A unique contribution of the North Carolina State University researchers is in using a powerful statistical method called “design of experiments” to guide the multi-parameter optimization of the DRILL device, resulting in identification of a sweet spot for optimal operation.

Fedorov and Torres hope to expand use of the DRILL device beyond Georgia Tech laboratories and further enhance its design. Among the near-term improvements planned is the addition of internal heating to accelerate the removal of solvent. “We see many additional improvements that will allow DRILL to further enhance the ESI-MS process,” said Fedorov. “We plan to continue evolving it as more labs start to use the device.”

In addition to those already named, the paper’s co-authors include Peter A. Kottke, Jung Y. Lee and Alex P. Jonke from Georgia Tech and Chinthaka A. Seneviratne and Elizabeth S. Hecht from North Carolina State University.

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM112662. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

CITATION: Peter A. Kottke, et al., “DRILL: An ESI-MS interface for improved sensitivity via inertial droplet sorting and electrohydrodynamic focusing in a swirling flow,” (Analytical Chemistry, 2017). http://dx.doi.org/10.1021/acs.analchem.7b01555.

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A phase I clinical trial conducted by Emory University in collaboration with researchers from the Georgia Institute of Technology has found that influenza vaccination using Band-Aid-like patches with dissolvable microneedles was safe and well-tolerated by study participants, was just as effective in generating immunity against influenza, and was strongly preferred by study participants over vaccination with a hypodermic needle and syringe. The microneedle patch vaccine could also save money because it is easily self-administered, could be transported and stored without refrigeration, and is easily disposed of after use without sharps waste. 

Results of the study are published June 27, 2017 in the medical journal The Lancet. The research was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. 

“Despite the recommendation of universal flu vaccination, influenza continues to be a major cause of illness leading to significant morbidity and mortality,” said first author Nadine Rouphael, M.D., associate professor of medicine (infectious diseases) at Emory University School of Medicine and principal investigator of the clinical trial. “Having the option of a flu vaccine that can be easily and painlessly self-administered could increase coverage and protection by this important vaccine.” 

The first-in-human clinical trial of the flu vaccine patches began in June 2015 with 100 participants aged 18-49 who were healthy and who had not received the influenza vaccine during the 2014-15 flu season. The study was conducted at the Hope Clinic of the Emory Vaccine Center in Atlanta. The study was carried out under an Investigational New Drug Application authorized by the FDA.

Participants were randomized into four groups: (1) vaccination with microneedle patch given by a health care provider; (2) vaccination with microneedle patch self-administered by study participants; (3) vaccination with intramuscular injection given by a health care provider; and (4) placebo microneedle patch given by a health care provider.

“People have a lot of reasons for not getting flu vaccinations,” said senior co-author Mark Prausnitz, Ph.D., Georgia Tech Regents professor of chemical and biomolecular engineering. “One of the main goals of developing the microneedle patch technology was to make vaccines accessible to more people. Traditionally, if you get an influenza vaccine you need to visit a health care professional who will administer the vaccine using a hypodermic needle. The vaccine is stored in the refrigerator, and the used needle must be disposed of in a safe manner. With the microneedle patch, you could pick it up at the store and take it home, put it on your skin for a few minutes, peel it off and dispose of it safely, because the microneedles have dissolved away. The patches can also be stored outside the refrigerator, so you could even mail them to people.”

Study results showed that vaccination with the microneedle patches was safe, with no adverse events reported. Local skin reactions to the patches were mostly faint redness and mild itching that lasted two to three days. No new chronic medical illnesses or influenza-like illnesses were reported with either the patch or the injection groups. Antibody responses generated by the vaccine, as measured through analysis of blood samples, were similar in the groups vaccinated using patches and those receiving intramuscular injection, and these immune responses were still present after six months. More than 70 percent of patch recipients reported they would prefer patch vaccination over injection or intranasal vaccination for future vaccinations. 

No significant difference was seen between the doses of vaccine delivered by the health care workers and the volunteers who self-administered the patches, showing that participants were able to correctly self-administer the patch. After vaccination, imaging of the used patches found that the microneedles had dissolved in the skin, suggesting that the used patches could be safely discarded as non-sharps waste. The vaccines remained potent in the patches without refrigeration for at least one year.

The microneedle patches used in the study were designed at Georgia Tech and manufactured by the Global Center for Medical Innovation in Atlanta. 

Prausnitz has been working for many years to develop the microneedle patch technology. “It’s very gratifying and exciting to have these patches tested in a clinical trial, and with a result that turned out so well. We now need to follow this study with a phase II clinical trial involving more people, and we hope that will happen soon.”

The researchers also are working to develop microneedle patches for use with other vaccines, including measles, rubella and polio.

“From the very start of this project,” said Prausnitz, “our team at Georgia Tech has been working with the Emory team to develop the microneedle patches, and the success of the project has been due to the strong collaboration between Georgia Tech engineers and the bioscience and medical experts at Emory.” Prausnitz holds the J. Erskine Love Jr. Chair in the School of Chemical and Biomolecular Engineering.

The authors summarized: “Influenza vaccination using microneedle patches is well-tolerated, well-accepted, and results in robust immunologic responses, whether administered by health care workers or by the participants themselves. These results provide evidence that microneedle patch vaccination is an innovative new approach with the potential to improve current vacination coverage and reduce immunization costs.” 

In addition to Rouphael and Prausnitz, other study authors include co-senior author Mark J. Mulligan, M.D., executive director of the Hope Clinic of the Emory Vaccine Center; Emory researchers Michele Paine, Regina Mosley, Paula M. Frew, Tianwei Yu, Natalie J. Thornburg, Sarah Kabbani, Lilin Lai, Elena V. Vassilieva, Ioanna Skountzou, and Richard W. Compans; and Georgia Tech researchers Sebastien Henry, Devin V. McAllister, Haripriya Kalluri, and Winston Pewin. 

This study was funded by a grant from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (U01 EB012495). One of the researchers received support through a training grant from the National Institute of Allergy and Infectious Diseases (T32 AI074492). The Georgia Research Alliance provided instrumentation support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsoring agencies.

Prausnitz has co-founded a company called Micron Biomedical that is licensing patents related to this study. Micron Biomedical is poised to move the microneedle patch technology forward, bring it further into clinical trials, commercialize it and ultimately make it available to patients. 

Prausnitz and several other Georgia Tech researchers are inventors of the microneedle patch technology used in this study and have ownership interest in Micron Biomedical. They are entitled to royalties derived from Micron Biomedical’s future sales of products related to the research. These potential conflicts of interest have been disclosed and are overseen by Georgia Institute of Technology and Emory University. 

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The symposium, organized by the National Academy of Engineering, gathers what the academy calls “exceptional” engineers from 30 to 45 years old to facilitate “cross-disciplinary exchange and promote the transfer of new techniques and approaches across fields in order to sustain and build U.S. innovative capacity.”

“The Frontiers of Engineering program brings together a particularly talented group of young engineers whose early-careers span different technical areas, perspectives and experiences,” said NAE President C. D. Mote, Jr. “But when they come together in this program, their mutual excitement is palpable, and a process of creating long-term benefits to society is often initiated.”

It’s a highly competitive and prestigious invitation, according to the National Academy of Engineering news release about the event.

“It is a privilege to be selected to join the Frontiers of Engineering Symposium,” said Kwong. “I am excited about the opportunity to interact with the brightest young minds within the engineering community, and exchange ideas across seemingly disparate disciplines.”

For 2017, the symposium will focus on the latest advances in four areas: mega-tall buildings and other future places of work, unraveling the complexity of the brain, energy strategies to power our future, and machines that teach themselves.

Kwong’s own research program is conducted at the interface of engineering and immunology. He and his multidisciplinary team develop nanotechnologies that interact with immune cells, enabling new applications in biomedical diagnostics and cell-based therapies. He has ten issued or pending patents and has launched one startup company.

“I often remind my lab that as bioengineers, we need to develop fluency in multiple academic languages before we can begin to innovate solutions to the most important problems in society” said Kwong. “I aim to bring my unique background in the physical and life sciences, and entrepreneurship to the fold.”

Invited participants for 2017 include three Georgia Tech assistant professors, as well as rising stars from organizations like Google, DARPA, 3M, IBM research labs, Lawrence Livermore National Laboratory, and others.

The 2017 US Frontiers of Engineering program will be hosted by United Technologies Research Center in East Hartford, Conn., September 25-27.

Media Contact:

Walter Rich
Communications Manager
Wallace H. Coulter Department of Biomedical Engineering

They were so inspired, in fact, that they made a life-changing decision: to make a naming gift that will advance research in biomedicine and biosciences and leave an enduring legacy at Georgia Tech.

Opened in 2015, EBB embodies collaboration. It was designed specifically to bring together researchers from different disciplines so that, as a community, Georgia Tech faculty and students drawn from biology, chemistry, and engineering can elevate our understanding of living systems and bring about new cures for diseases. It houses the Children’s Pediatric Technology Center, a research partnership with Children’s Healthcare of Atlanta and Emory University. And it was made possible thanks to the investment of the State of Georgia, the Institute, and private philanthropy.

“We believe that the next big area for Georgia Tech is at the intersection of engineering and biosciences,” the Krones explained. “There is so much we need to do: find cures for cancer, diabetes, and other chronic diseases. And that will require a new era in cooperation and collaboration. We hope that our gift will help propel Tech to a global leadership role in solving the most difficult human engineering problems that affect us all.”

The Roger A. and Helen B. Krone Engineered Biosystems Building is organized around research neighborhoods: chemical biology, cell and developmental biology, and systems biology, and provides 219,000 square feet of shared laboratories, offices, and common spaces. Stairs alternate on various floors, encouraging people to move within the neighborhoods and interact with one another. Small and informal meeting areas are located near the stairwells, to further encourage interactions among the 140 faculty members and 1,000 graduate students who work there. 

“I have often said that if cancer is cured at Georgia Tech, it will happen in the facility we have been calling EBB,” said Gary S. May, EE 1985, dean and Southern Company Chair in the College of Engineering. “I could not be more pleased to say that that potential now exists for the Krone Building. Roger and Helen Krone have been great benefactors to Tech. It is fitting that this generosity is now permanently reflected in the building that will bear their name.”

Paul M. Goldbart, dean and Betsy Middleton and John Clark Sutherland Chair in the College of Sciences, echoed May’s sentiments. “I believe I speak for all of the researchers whose work will reach new heights as a result of the Krone Building, as well as all of the people whose lives and health will be enriched because of this work, when I say how immensely grateful we are to Roger and Helen Krone and all others who have made this ‘temple of science and engineering’ possible.” 

Roger Krone is the CEO of Leidos, a leader in science and technology solutions in defense, intelligence, homeland security, and civil and health markets. Before joining the company, he was president of Network and Space Systems for The Boeing Company, and was vice president and treasurer of McDonnell Douglas at the time of its 1997 merger with Boeing. Krone first began working at McDonnell Douglas in 1992 as director of financial planning after spending 14 years at General Dynamics. 

Helen Krone is secretary, treasurer, and financial manager for the Krone Foundation. She is a member of the board of trustees for the Mountain Retreat Association, which manages the Montreat Conference Center, a national Presbyterian conference center in North Carolina. 

For both of them, philanthropy is not just something they do, but an essential part of who they are. Over many years they have given generously, especially to the universities that shaped their lives — Helen’s alma mater is the University of Texas at Austin, and Roger holds a master’s degree in aerospace engineering from the University of Texas at Arlington and an MBA from Harvard Business School. 

“Our success is the integral product of all of the investments that people and institutions have made in us over the past 40 years,” they said. “The transformation we have watched at Georgia Tech over those same 40 years has been the direct result of the commitment that alumni have made in the Institute. The university that Tech will become will be a direct result of the lasting commitment we all make.” 

In 2015, the couple made an estate gift for faculty support in the Daniel Guggenheim School of Aerospace Engineering that pushed that school past its campaign goal in the final months of Campaign Georgia Tech. For 43 consecutive years, they have given to Roll Call. But it’s not only about financial support. Roger Krone currently serves on the board of the Georgia Tech Foundation and he has been a member and chair of the Georgia Tech Advisory Board. He also served as an ex-officio member of the Campaign Steering Committee.

“My education didn’t end with my graduation,” he explained. “My lifelong association with Tech through continuing education, lectures, seminars, recruiting, advisory boards, and, of course, athletics, have continuously enriched my life.”

Cancer cells kill most often by crawling away from their original tumors to later re-root in vital parts of the body in a process called metastasis. Now, a research team led by the Georgia Institute of Technology has developed a new treatment to thwart cancer's spread through the body by, in a sense, breaking cancer cells’ legs.

Cancer cells often cover themselves with bristly leg-like protrusions that enable them to creep. The researchers have used minuscule gold rods heated gently by a laser to mangle the protrusions, according to a new study. The treatment prevented cell migration, a key mechanism in metastasis, in experiments on common laboratory cultures (in vitro) of cancerous human cells.

The method could potentially, in the future, offer clinicians going after individual tumors a weapon to combat cancer’s deadly spread at the same time. The medical field is currently less than well-equipped to stop metastasis.

“If cancer stays in a tumor in one place, you can get to it, and it’s not so likely to kill the patient, but when it spreads around the body, that’s what really makes it deadly,” said lead researcher Mostafa El-Sayed, Julius Brown Chair and Regents Professor at Georgia Tech’s School of Chemistry and Biochemistry.

The treatment can also easily kill cancer cells, but in this experiment, it was vital to specifically show that it greatly slowed cell migration. The method is not scheduled for human testing.

Halting cancer softly

The experimental treatment also spared healthy cells, in these and in prior experiments, making the method potentially much less taxing on patients than commonly used chemotherapy. In past tests in animal models, the researchers have uncovered no toxic side effects from the gold used in the treatment, and have found no observable damage to healthy tissue from the low-energy laser.

And they did not see recurrence of the treated cancer.

“The method appears to be very effective as a locally administered treatment that also protects the body from cancer’s spread away from the treated tumors, and it is also very mild, so it can be applied many times over if needed,” El-Sayed said.

El-Sayed, co-lead author Ronghu Wu, and first authors Yue Wu and Moustafa Ali published the results of their current in vitro experiments, a new development in photothermal gold nanorod therapy, on June 26, 2017, in the Proceedings of the National Academy of Sciences. The research was funded by the National Science Foundation and the National Institutes of Health.

How it works: Icky legs

To understand how the treatment works, let’s take a close-up look at a cell and some things that happen to it in malignant cancer.

Many people think of cells as watery balloons -- fluid encased in a membrane sheath with organelles floating around inside. But that picture is incomplete. Cells have support grids called cytoskeletons that give them form and that have functions.

The cytoskeletons also form bristly protrusions called filopodia, which extend out from a weave of fibers called lamellipodia that are on the cell’s fringes. The protrusions normally help healthy cells shift their location in the tissue that they are part of.

But in malignant cancer, normally healthy cell functions often lunge into destructive overdrive. Lamellipodia and filopodia are wildly overproduced.

“All these lamellipodia and filopodia give the cancer cells legs,” said Yue Wu, a graduate student in bioanalytical chemistry. “The metastasis requires those protrusions, so the cells can travel.”

How it works: Sticky rods

The gold nanorods thwart the protrusions in two ways. The rods are comprised of a small collection of gold atoms – nano refers to something being just billionths of meters (or feet) in size.

First, El-Sayed’s nanorods are introduced locally, where they encumber the leggy protrusions on cancerous cells. The rods are coated with molecules (RGD-peptides) that make them stick specifically to a type of cell protein called integrin.

“The targeted nanorods tied up the integrin and blocked its functions, so it could not keep guiding the cytoskeleton to overproduce lamellipodia and filopodia,” said Yan Tang, a postdoctoral assistant in computational biology who worked on the study. The binding of the integrin alone slowed down the migration of malignant cells.

But healthy cells were not targeted. “There are certain, specific integrins that are overproduced in cancerous cells,” said Moustafa Ali, one of the study’s first authors. “And you don’t find them so much in healthy cells.”

How it works: Gentle laser heating

In the second phase, researchers hit the gold nanoparticles with a low-energy laser of near-infrared (NIR) light. It brought the migration of the cancer cells to an observable halt.

“The light was not absorbed by the cells, but the gold nanorods absorbed it, and as a result, they heated up and partially melted cancer cells they are connected with, mangling lamellipodia and filopodia,” Ali said. “It didn’t kill all the cells, not in this experiment. If we killed them, we would not have been able to observe whether we stopped them from migrating or not.”

If desired, the treatment can also be adjusted to kill the cells.

Early experiments in animal models in vivo with hotter lasers didn’t work as well.  “That caused inflammation, which made it possible to heat one time only,” Ali said. “As a result, that high temperature would wipe out many cancer cells, but not all of them. Some hidden ones might have survived, and also still been able to migrate.”

“This gentle laser didn’t burn the skin or damage tissue, so it could be dosed multiple times and more thoroughly stop the cancer cells from being able to travel,” said researcher Ronghu Wu.

Medical possibilities

The researchers presently envision treating head, neck, breast, and skin cancers with direct, local nanorod injections combined with the low-power near-infrared laser, which can hit the gold nanorods 2-3 centimeters (a bit under or over an inch) deep inside tissue. “But it could go as deep as 4-5 centimeters,” Ali said.

Deeper tumors could conceivably be treated with deeper injections of nanorods. “Then you’d need to go in with a fiber optic or endoscopic laser,” El-Sayed said. Injecting the nanorods directly into the bloodstream as a broad treatment would not currently be a viable option.

El-Sayed’s group has previously published in vivo experiments in mice in the Proceedings of the National Academy of Sciences together with Emory University School of Medicine. That study showed no observable toxicity from the gold in mice 15 months after treatment.

“A lot of it ended up in the liver and spleen,” El-Sayed said. “But the functions of these organs appeared intact upon examination, and treated mice were alive and healthy over a year later.”

Presidential honors

Mostafa El-Sayed is one of the world’s most highly decorated and cited living chemists, and a pioneer of nanoscience and technology. Among his many recognitions are the President’s National Medal of Science, awarded by President George W. Bush, and the Priestley Medal, the American Chemical Society’s highest honor. President Barack H. Obama appointed El-Sayed to the President’s National Medal of Science Committee. El-Sayed also participated in the nomination of chemistry Nobel Laureate Ahmed Zewail.

El-Sayed is known throughout physical chemistry for “El-Sayed’s Rule,” which handles complexities of electron spin orbits, and which has found a lasting place in photochemistry textbooks. After losing his wife to cancer in 2005, El-Sayed dedicated his knowledge and research to ending the scourge.

Also read: Cancer and Technology

Also read: Punching Cancer with RNA Knuckles

The following authors also contributed to this research: Haopeng Xiao and Tiegang Han from Georgia Tech, and Kuangcai Chen and Ning Fang from Georgia State University. This research was funded by the National Science Foundation Division of Chemistry (grants 1608801, CAREER Award CHE-1454501), and the National Institutes of Health Nanotechnology Study Section (grant 1R01GM115763). Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.

Though he couldn’t have known it at the time, Darwin was describing the kind of enlightened (and evolved) self-interest that can also be found in a manmade entity such as the long bio-research partnership between the Georgia Institute of Technology (with its multidisciplinary engineering heft) and Emory University (with its sprawling medical school and clinical research capacity).

 It’s a partnership that has produced biomedical discoveries for decades, one of the most dramatic being the recent successful human clinical trial of a microneedle patch for flu vaccines, a project headed up for years by Georgia Tech researcher Mark Prausnitz, whose own appraisal echoed Darwin’s 19th century assertion: "From the very start of this project, our team at Georgia Tech has been working with the Emory team to develop the microneedle patches,” Prausnitz said. “And the success of the project has been due to the strong collaboration between Georgia Tech engineers and the bioscience and medical experts at Emory."

                                          * * *

The Georgia Institute of Technology and Emory University are connected by twisting ribbons of asphalt, five or six miles long depending on your destination. It’s a route that Bob Guldberg, executive director of the Petit Institute for Bioengineering and Bioscience at Georgia Tech, knows really well.

“When I started I was going to Emory almost every day for my in vivo studies, and to be honest, if it wasn’t for Emory, I would not be at Georgia Tech,” says Guldberg, who came to Atlanta fresh from the University of Michigan in 1996, and has been a grateful beneficiary and influential proponent of another kind of connection between the two universities – a longstanding, ever-evolving biomedical research partnership.

Guldberg arrived as an up and coming leader in orthopedic musculoskeletal research, which didn’t really have a presence at Georgia Tech at the time, “but there were potential collaborators in orthopedics at Emory," he says.

So he joined the unique and growing research partnership that existed between a private university (Emory) and a public one (Tech).

A year after Guldberg arrived, that partnership took a bold and historic step with the creation of a new academic unit. The Wallace H. Coulter Department of Biomedical Engineering (BME, launched in 1997) was the result of several things converging in the ecosystems of Emory and Georgia Tech.

This joint academic department formally linking private and public institutions is the first of its kind and rated among the best in the world. BME was the organic offspring of earlier developments, such as the Emory/Georgia Tech Biomedical Technology Research Center and its seed grant program, which nurtured an expanding faculty interest in collaborative research when it was established in 1987.

“That seed grant program was absolutely essential and its influence on success of the Emory-Georgia Tech partnership can’t be underestimated,” says Bob Nerem, founding director of the Petit Institute, which launched in 1995. “It provided a foundation for everything else that has taken place since.”

Airport Diplomacy

As Mike Johns remembers it, a conversation in 1996 on an airport escalator with Nerem ultimately led to the creation of a joint BME department. Johns had recently been named executive vice president director of Emory’s Woodruff Health Sciences Center and CEO of its Healthcare System.

Nerem had been at Georgia Tech since 1987, playing a leading role in growing the collaborative bioengineering research efforts between the two universities. Now he was settling into his role as director of the fledgling Petit Institute, a multidisciplinary research center that strengthened the bond between Georgia Tech and Emory, with its faculty from both universities and focus on a team approach.

Johns and Nerem had been attending a meeting in Washington, D.C., “and as we were coming up the escalators I said, ‘Hey, Bob, I really think Emory and Georgia Tech need to come together and form a biomedical engineering department. We don’t have an engineering school and you guys don’t have a medical school. This is something we can do together,’” Johns recalls.

So Nerem put him in touch with Georgia Tech’s provost at the time, Mike Thomas. “We agreed that if we were going to do something in any formal way, we needed a task force and that the logical person to lead it was Don Giddens,” says Nerem. “We had to bring him back from Hopkins to Atlanta.”

Giddens left Georgia Tech in 1992 to become Dean of Engineering at Johns Hopkins University, where he worked closely with Mike Johns, who had been dean of the Johns Hopkins School of Medicine.

“The opportunity to work with Mike Thomas and Mike Johns and build this thing from scratch was very appealing,” says Giddens, who led the task force through the summer of 1997. The team wrapped up its report and sent its recommendations to the Georgia Board of Regents, as well as Emory’s Board of Trustees. “Then things started moving very quickly.”

By September, the department was approved, Giddens was named as its inaugural chair, and a new era of collaboration had begun.

Team Bioscience

In 1889, an Emory graduate and former Emory president, Isaac Stiles Hopkins, became Georgia Tech’s first president. Then it took almost a hundred years for the two institutions to embark on an official partnership. When that happened, bioengineering and biomedical research were the sparks.

Interest in applying engineering principles to biomedical research was percolating at Georgia Tech by the mid 1970s, Giddens says.

“It was people like myself, Ray Vito, Ajit Yoganathan, Art Koblasz, and a couple of others,” recalls Giddens, who eventually became dean of Georgia Tech’s College of Engineering (2002-2011). “A lot of that interest was clustered within the ‘mechanics department,’ which no longer exists, and electrical engineering. Georgia Tech faculty would interact and collaborate with Emory faculty.”

Giddens was among the researchers who banded together to form the Georgia Tech Bioengineering Center, “which was kind of a key cornerstone for building the rest of what’s happened,” says Giddens. He and his colleagues had some ideas about research and education opportunities between the two universities. “One of the first things we did was to approach Emory,” Giddens adds.

Bill Todd, a Georgia Tech graduate who was Emory’s assistant vice president of health affairs at the time, remembers getting a call from his boss, Charles Hatcher (Johns’ predecessor at Emory). Hatcher had been talking to Georgia Tech’s Vice President for Research Tom Stelson, and he reached out to Todd, who recalls, “He said, ‘Georgia Tech and Emory have been talking for years about collaborating in a more formal way. Everybody says the right words, but we’ve got to do something deliberate.’ He told me to connect with Don Giddens, and leadership at both schools promised support and money to move forward in a structured, intentional way.”

The way forward led to the establishment in 1987 of the Emory/Georgia Tech Biomedical Technology Research Center and the influential seed grant program.

 “That was our venture into the first phase of the Georgia Tech-Emory relationship on a formal basis,” says Yoganathan, Regents professor and Wallace H. Coulter Distinguished Faculty Chair in Biomedical Engineering. “And I’m not even sure if ‘venture’ is the right word. Maybe ‘adventure’ is correct, because we were really trying out something new.”

Todd and Giddens understood the potential of collaborative research between the two universities – one a hotbed of bioengineering and biomedical research, the other home to one of the nation’s leading medical schools and healthcare systems. So they devised a seed grant that required faculty from both institutions to work together.

“That seed grant was catalytic in getting researchers to move into the biomedical research environment,” notes Wayne Alexander, former chair of Emory’s Department of Medicine.

One of those researchers was Nerem, who came to Georgia Tech after being recruited from the University of Houston, where he chaired the Department of Mechanical Engineering. “One of the main attractions for me coming to Georgia Tech was the fact that the seed grant had been set up,” Nerem says.

Years later, Nerem’s successor at the Petit Institute could say the same thing. Guldberg credits the program with catalyzing his sustained collaborative research with Emory’s Bob Taylor (division director of cardiology). “Our initial $25,000 Georgia Tech/Emory seed grant led to four funded multi-investigator R01 awards from NIH, probably totaling about $10 million in funding,” he says. Just as importantly, it’s helped train the next generation of investigators. For example, there’s Craig Duvall, co-advised as a student by Guldberg and Taylor, and now an associate professor of BME at Vanderbilt, working on NIH-funded research.  

The seed grant experience was also particularly educational for Todd, who took the idea with him when he became the founding president and CEO of the Georgia Research Alliance in 1990. “The Emory-Georgia Tech program was illustrative to me as we set up the GRA, because we were learning things – learning how to navigate the complexities of a joint venture, when two parties have their own sets of needs,” says Todd, now professor of practice in the Scheller College of Business at Georgia Tech.

Academic Standing

While the Georgia Tech/Emory seed grant program helped spur collaborative research, the two schools focused on academic pursuits, another objective of the biomedical research center, and began attracting the interest of major donors, like the Whitaker Foundation.

In 1993 the Emory-Georgia Tech partnership secured one of just three Whitaker Foundation Biomedical Engineering Program Development grants, which supported development of a Ph.D. program in bioengineering (BioE). The first faculty member recruited through that grant was Mark Prausnitz, the microneedle patch leading researcher, a long-time member of the Petit Institute who now holds the J. Erskine Love Chair in the School of Chemical Biomolecular Engineering.

Under Yoganathan’s guidance, the multidisciplinary BioE program soon became one of the top rated academic programs of its kind in the nation. Then, with the creation of the BME department in 1997 (it wasn’t named for Wallace H. Coulter yet), began a push to develop new academic programs, including graduate degrees in BME awarded jointly.

While he was dean of engineering at Johns Hopkins, Giddens guided the top ranked biomedical engineering department in the U.S. When he returned to Atlanta, he was charged with building a department from the ground up. The BME task force led by Giddens that summer of 1997 pitched the idea to Emory’s trustees, writing, “There is every reason to believe that Atlanta can be a national center for biomedical research and education if our two institutions pool capabilities. On the other hand, failure to act decisively at this time may create a handicap that will be difficult to surmount.”

They acted decisively, both Emory’s trustees and the University System of Georgia’s Board of Regents (which governs public universities, like Georgia Tech), approving the department in a matter of weeks.

The plan was to hire 15 to 18 new faculty within five years, and create a brand new graduate program. That task fell into Yoganathan’s capable hands, so he led the effort to map out a joint Ph.D. program in biomedical engineering, which was approved in 1999, while Paul Benkeser (currently senior associate chair of BME) led development of the undergraduate program. Students began enrolling in both programs in 2000, the same year the Whitaker Foundation granted a $16 million leadership development award.

“We knew the Whitaker Foundation wanted to support an undergraduate program,” Giddens says. “Their belief was that by developing an undergrad program, you ensure the permanence of the discipline.”

In 2001 the Georgia Tech/Emory Department of Biomedical Engineering was renamed for Wallace H. Coulter (one of the influential engineers of the 20^th century, who shaped the fields of automated cell analysis and hematology) when the Coulter Foundation committed $25 million to the department. The gift supported a department chair, faculty chairs at Georgia Tech and Emory, labs, graduate fellowships, undergraduate clinical education, and the Coulter Endowment for Translational/Clinical Research.

Learning Science

Early on in the life of the Emory-Georgia Tech BME venture, Giddens made one of the most significant moves of his career: he brought Wendy Newstetter, a learning scientist, to the department.

“I’d become aware of the cognitive and learning scientists that were working at Georgia Tech in the College of Computing and thought that since we were going to build a curriculum, undergraduate and graduate, maybe we could get them interested in collaborating and using us as guinea pigs,” Giddens says.

That move began a culture of innovation in education that still fuels the department today, according to Joe Le Doux, one of BME’s first faculty hires, and now the department’s associate chair of undergraduate learning and experience.

“Don had the foresight and vision for what BME could become as a major and as a discipline,” Le Doux says. Hiring a learning scientist like Newstetter, “was a bold move and made the statement that education and learning was a top priority in our program.”

Newstetter, now director of learning science research for the College of Engineering, developed a new way of teaching engineering based on problem-based learning (PBL), “a pedagogical approach that came from medical school, that we adapted to a biomedical engineering environment,” she says. “We were able to observe classes at Emory, which uses problem-based learning, and figure out what we wanted it to look like at Georgia Tech.”

They created an environment for undergraduate students that emphasized collaboration over competition, immersing students in real-world, complex problems. As student enrollment soared and faculty resources were stretched thin, grad students and post docs (and later, upper classmen among the undergrads) were recruited to serve as PBL facilitators.

There were no BME textbooks at the undergraduate level. “There was no curriculum that could be considered the curriculum for BME,” notes Larry McIntire, who became chair of the department after Giddens vacated the post to become dean of the College of Engineering. “We were fortunate to have some very creative people.”

The curriculum has evolved but the focus is still on PBL, more than ever. There are fewer lecture courses now in BME, and more design courses. The BME curriculum continues to get rave reviews nationally, which is manifested in annual department rankings. Over time, both the graduate and undergraduate programs have climbed in the rankings with the undergraduate program currently listed No. 1 on the U.S. News and World Report annual rankings and the graduate program No. 3.

“Innovative, problem-focused learning has always been part of our departmental DNA,” says Ross Ethier, a Petit Institute researcher and Georgia Research Alliance Eminent Scholar who became interim chair of BME after Ravi Bellamkonda left the post to become dean of engineering at Duke University the summer of 2016. “We’ve always encouraged our students to be fearless in their approach to complicated problems, not to be constrained by preconceived notions about what is or isn’t too difficult. We have worked hard to inculcate that mindset in students, so that they can go out there and do the things that will change the world, quite frankly.”

Beyond Borders

The Georgia Tech-Emory partnership gained further momentum in 1998 when the National Science Foundation awarded $12.5 million for establishment of the Georgia Tech/Emory Center for the Engineering of Living Tissues (GTEC). Headed by Nerem, that joint research center has evolved into its current incarnation, the Regenerative Engineering and Medicine research center, a collaboration of Emory, Georgia Tech, and the University of Georgia.

Two years later, success followed success as Emory and Georgia Tech, with support from the GRA, created EmTech Bio, a biotech incubator with lab space and scientific equipment for start-up and early-stage companies on the Emory Briarcliff campus.

Through the first decade of the 21^st century, the Georgia Tech-Emory partnership continued to attract large grants, especially from the National Institutes of Health, for nanotechnology research. In 2004, NIH made awards totaling $10 million to launch a multidisciplinary research program in cancer nanotechnology.

In 2005, the National Cancer Institute of NIH awarded $19 million to the two universities for the creation of the Emory-Georgia Tech Nanotechnology Center, one of seven National Centers of Cancer Nanotechnology Excellence. That same year, NIH awarded Tech and Emory scientists $11.5 million for a new program to create advanced nanotechnologies aimed at detecting and analyzing plaque at the molecular level.

“Our researchers were doing cutting edge research in nanotechnology before nanotechnology was being done by everyone. It brought us some high profile grants and gave us a lot of visibility in the scientific community,” says McIntire, who came to Georgia Tech from Rice University in 2003, as the U.A. Whitaker Building (home of BME on the Tech campus, next door to the Petit Institute) was still getting its final touches, while over at Emory, labs and offices were renovated for BME in the Woodruff Memorial Research Building.

In 2007, the NIH awarded more than $31 million over five years to a partnership that included Emory, Tech, the Morehouse School of Medicine, and Children’s Healthcare of Atlanta. The partnership focused on accelerating the translation of lab discoveries into healthcare innovations for patients. The result is the Atlanta Clinical and Translational Science Institute (ACTSI).

Biomedical Bridge

Ravi Bellamkonda, who was the third Coulter Department chair (2013-2016) always thought of BME as, “the firm, successful bridge between the two universities, a corridor that links Georgia Tech and Emory.”

BME remains one of a number of powerful links between Emory and Tech, whose partnership continues to draw major support, such as the $15.7 million grant from the Atlanta-based Marcus Foundation in early 2016 to create the Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M) on the Georgia Tech campus.

Directed by Petit Institute researcher and BME Professor Krishnendu Roy, the new center will partner with institutions around the country, such as Emory and the University of Georgia, among others.

Meanwhile, leadership at both universities envision even more of this kind of high-octane collaboration. It’s vital. What used to be a pioneering notion has become something of a necessity.

“Team science is increasingly a strategic goal for our researchers and is certainly a focus of our federal funders,” says David Stephens, interim dean of Emory’s School of Medicine and vice president for research, Woodruff Health Sciences Center. “The Emory-Georgia Tech partnership is perfectly suited for that. So I’d like to see even more emphasis on team science, involving a broader group of faculty in more areas of health care.”

The two schools began a new chapter with the announcement in May that Susan Margulies had been named chair of the Coulter Department (and a GRA Eminent Scholar in Injury Biomechanics). Currently a professor of bioengineering at the University of Pennsylvania, Margulies is the fourth chairperson and first woman to head what is now the largest BME department in the country with more than 1,500 undergraduate and graduate students.

“Dr. Margulies will be an outstanding addition and leader for our joint department of biomedical engineering,” says Stephens. “Throughout her career, she has distinguished herself as an educator, scientist, mentor, and a national and international leader in the biomedical sciences, and I look forward to working with her in our many shared initiatives.”

Although the leadership has changed over the years, one constant has been the continual commitment to the Georgia Tech/Emory partnership.  In January of this year, Jon Lewin, the president, CEO, and chairman of Emory Healthcare visited Georgia Tech for a half day discussion of the partnership history and future opportunities.

Lewin envisions an expansion of BME, as well as regenerative medicine and immuno-engineering research, “and embracing new joint programs in critical areas of medicine, such as cancer and neuroscience, and emerging fields of antibiotic resistance and the microbiome, as well as precision medicine – taking advantage of health care informatics and big data is an obvious area of future collaboration,” he says.

“I believe we can have an even greater impact on advancing biomedical research generally and on patient outcomes here in Atlanta and globally,” adds Lewin. “We also can jointly continue to impact the economies of Atlanta and Georgia through research dollars, faculty recruitment, retention of talented graduates, and startup companies. I see an even brighter future for our partnership.”

The technique, which has been validated against a drug-resistant bacterial strain, identifies compounds that target two or more receptor sites on proteins that inhibit a key cellular function. To obtain resistance to drug compounds developed with the technique, the microbes would have to simultaneously develop mutations in all the receptor pockets targeted by the drug – a challenge much more significant than developing resistance in a single receptor site.

Researchers from the Georgia Institute of Technology and Harvard University believe the technique could provide a new general approach for battling drug resistance that may potentially also be applied to cancer cells and viruses which also develop drug resistance. The research, supported by the National Institutes of Health, was reported May 19 in the journal ACS Chemical Biology.

“We have developed an entirely novel mechanism for increasing antibiotic effectiveness,” said Jeffrey Skolnick, director of Georgia Tech’s Center for the Study of Systems Biology and a Georgia Research Alliance Eminent Scholar in Computational Systems Biology “The problem of emerging antibiotic resistance is a major health care crisis, and we think this approach could allow the rapid design of new classes of molecules that would be able to maintain their effectiveness longer, allowing us to stay one step ahead of the bugs.”

Antibiotic resistance often develops when proteins – often enzymes – mutate the receptor pockets that allow the drugs to bind to the protein. Bacterial populations often include individuals that have these mutations randomly, and when antibiotics kill off the susceptible cells, the population of those with the specific mutation grows. In order to control these resistant bacteria, doctors must employ a drug compound that targets a different receptor or different binding site on a key bacterial protein.

The technique identified three classes of inhibitor drugs that targeted both primary and secondary receptor pockets on the dihydrofolate reductase (DHFR) enzyme in a drug-resistant strain of Escherichia coli (E. coli). DHFR is necessary for the synthesis of important cellular building blocks, and is a classical target for antibiotics. Without production of these compounds, bacteria cannot reproduce.  

Using their algorithm, Skolnick and his Georgia Tech collaborators identified 10 potentially useful drug compounds and prioritized compounds from the three categories – stilbenoid, deoxybenzoin and chalcone family of compounds – for their ability to target a secondary receptor pocket. Interestingly, one of the molecules was resveratrol which is found in red wine and which has been reported to have anti-aging and anti-cancer effects. In the laboratory, the researchers confirmed that the commercially available compounds could indeed bind with DHFR.

But the real test was whether the compounds would work on living bacteria. To evaluate that, the Georgia Tech researchers worked with Eugene Shakhnovich, a professor in the Department of Chemistry and Chemical Biology at Harvard University. Shakhnovich and his colleagues confirmed that the drug compounds shut down the production of folates in the drug-resistant E. coli, dramatically slowing the growth of the bacterium. They also showed that the addition of folates to the bacterial population allowed the bugs to survive despite treatment by the DHFR-inhibiting drugs.

“We tested the compounds in vitro with purified variants of the enzyme,” Shakhnovich said. “We engineered E. coli strains that carry escape mutations in the folA locus – which encodes DHFR – on their chromosomes and proved that the newly-found compounds effectively inhibit growth in both wild-type and escape mutant strains of DHFR, albeit at high concentrations.”

Because it is a relatively small protein with well-defined biophysical properties, DHFR “represents a desirable model to explore the genotype-phenotype relationship between biophysical properties of the enzyme and the fitness and evolution of a microorganism,” Shakhnovich added.

As a next step, Skolnick would like to test the principle on other proteins essential to other microorganisms to see if two or more binding pockets can be targeted. That could require development of new therapeutic molecules able to attack the microbial targets. Ultimately, the technique could be used to shut down other avenues of antibiotic resistance, including the ability of cells to break down drugs or eject them before they can bind.

If the technique proves successful in other laboratory studies, testing with an animal model would be necessary to determine whether it can be beneficial in living organisms.
DHFR has been targeted for anti-cancer drugs, and Skolnick is hopeful that the two-receptor technique may prove useful in developing new chemotherapy agents that could fight off the resistance that often renders them useless.

Skolnick believes the approach may help scientists stay ahead of bacterial resistance by providing a technique to rapidly develop new drugs. The compounds would be used in combination therapies to further guard against development of resistance.

“We are always going to be at war with microbes,” he said. “The bacterial system is going to evolve to respond to new antibiotics, so we have to keep targeting something else so the system never gets to evolve resistance. It’s likely that we’ll need to use combination therapies that use multiple drugs to eliminate the development of resistance.”

This project was funded by 1R35GM118039 and 1RO1068670 (to Shakhnovich) of the Division of General Medical Sciences of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

CITATION: Bharath Srinivasan, Joa?o V. Rodrigues, Sam Tonddast-Navaei, Eugene Shakhnovich, and Jeffrey Skolnick, “Rational Design of Novel Allosteric Dihydrofolate Reductase Inhibitors  Showing Antibacterial Effects on Drug-Resistant Escherichia coli Escape Variants,” (ACS Chemical Biology, 2017) http://dx.doi.org/10.1021/acschembio.7b00175

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The arrays' inventors say they could be harnessed to make nanotech sensors or amplifiers. Potentially, they could be combined to form logic gates, the parts of a molecular computer.

The arrays' properties are scheduled for publication online by Science.

The DNA machines can relay discrete bits of information through space or amplify a signal, says senior author Yonggang Ke, Ph.D., an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Emory and Georgia Tech.

"In the field of DNA-based computing, the DNA contains the information, but the molecules are floating around in solution," says Ke, who also is a researcher at the Petit Institute for Bioengineering and Bioscience at Georgia Tech. "What's new here is that we are linking the parts together in a physical machine."

Similarly, several laboratories have already made nanotech machines such as tweezers and walkers out of DNA. Ke says his team's work with DNA arrays sheds light on how to build structures with more complex, dynamic behaviors.

The arrays' structures look like accordion-style retractable security gates. Extending or contracting one unit pushes nearby units to change shape as well, working like a domino cascade whose tiles are connected.

The arrays' units get their stability from the energy gained when DNA double helices stack up. To be stable, the units' four segments can align as pairs side by side in two different orientations. By leaving out one strand of the DNA at the edge of an array, the engineers create an external trigger. When that strand is added, it squeezes the edge unit into changing shape (see illustration).

To visualize the DNA arrays, the engineers used atomic force microscopy. They built rectangular 11x4 and 11x7 arrays, added trigger strands and could observe the cascade propagate from the corner unit to the rest of the array.

The arrays' cascades can be stopped or resumed at selected locations by designing break points into the arrays. The units' shape conversions are modulated by temperature or chemical denaturants.

For reference, the rectangular arrays are around 50 nanometers wide and a few hundred nanometers long - slightly smaller than a HIV or influenza virion.

To build the DNA array structures, the engineers used both origami (folding one long "scaffold" strand with hundreds of "staple" strands) and modular brick approaches. Both types of arrays self-assemble through DNA strands finding their complimentary strands in solution. The origami approach led to more stable structures in conditions of elevated temperature or denaturant.

In the Science paper, the engineers showed that they could build rectangles and tubes of array units. They also include a cuboid that has three basic conformations, more than the two-dimensional array units with two conformations. Ke says his team is working on larger, more complex machines with three-dimensional shapes, which can be made using the same basic design principles.

The laboratory of Chengde Mao, PhD in Purdue University's Department of Chemistry contributed to the paper. The co-first authors of the paper are postdoctoral fellow Jie Song, PhD, now at Shanghai Jiaotong University, postdoctoral fellow Pengfei Wang, PhD, and Purdue graduate student Zhe Li.

The research was supported by the National Science Foundation (CAREER DMR-1654485, CMMI-1437301), the Marcus Foundation, the Office of Naval Research (N00014-15-1-2707) and the National Natural Scientific Foundation of China (21605102).

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All muscles typically have slight oscillations at the same time — less than three per second or three Hz — when they’re used. This is the common motor drive.

This common drive may also be a reason why stroke survivors have trouble keeping their hands from becoming rigid and shaking. Only when you control both sets of muscles individually, or overcome this common drive, the rigidity and wobbling may stop.

Georgia Institute of Technology researchers wanted to learn why some people are better than others at controlling joint stiffness by co-contracting opposing muscles to overcome this common drive. They also wanted to know if that skill could be taught. If so, it could lead to more effective rehabilitation exercises for stroke survivors or people with Parkinson’s disease.

In a new study, the researchers set up an experiment for healthy young adults. They were tasked with flexing their bicep muscles and maintaining that activation at a designated level while also extending their triceps and keeping them steady at a different level. By wearing EMG sensors, the researchers were able to determine who was more effective in steady co-contraction.

“The opposing muscles fought against each other to maintain different activation levels,” said Minoru Shinohara, an associate professor in the School of Biological Sciences at Georgia Tech. “It wasn’t easy. Some participants were actually sweating after just 30 seconds, struggling to keep both muscles activated and consistent at different levels.”

The people who were worst at the experiment were unable to reduce the synchronized oscillations from both muscles. They rose and fell at the same time.

“In contrast, better performers were able to dissociate the signal to both muscles and control them individually,” said Shinohara. “They overcame the mind’s willingness to send synchronized signals across muscles. They activated individually to better control both.”

The next part of the experiment was to see if the healthy adults could train their muscles to more easily overcome the common drive. A third of the participants were trained for dissociated co-contraction — to flex and contract both muscles simultaneously but at different levels, back and forth, for an hour. Others worked on one muscle for a while, then switched to the other. The third group rested for 60 minutes.

Afterward, everyone did the first test again. The improvement was the same across groups. Those who did nothing for an hour were just as successful (or not) as those who practiced, simply due to familiarization with the test.

“If you practice anything specific for an hour, you’re likely to see specific improvement,” said Shinohara. “But there were no specific improvements with the dissociation practice. This means that the common drive is deeply embedded into the mind. It would take a long time for healthy adults to efficiently dissociate their muscles.”

And that may partially explain why stroke survivors are slow to see any improvement after extensive rehab.

“If healthy adults have trouble controlling their muscles individually, we shouldn’t be surprised that those who always struggle to control their muscles would have an even more difficult experience. An hour isn’t enough, which isn’t too surprising. But it’s important that people don’t give up if it takes a while to progress.”

The paper, “Slow intermuscular oscillations are associated with cocontraction steadiness,” is currently published ahead of print in the journal Medicine & Science in Sports & Exercise.

The study is supported by the National Science Foundation (IIS-1317718). Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsor.

But this time, there was some added excitement over future potential with the introduction of an innovative, additional granting mechanism from the Georgia Research Alliance (GRA). The Allen Fund, a $1 million gift (from Dr. J. David Allen and family), to be disbursed over 10 years to the GRA to advance cellular manufacturing research and development at REM’s three member institutions.

“The Allen gift represents a significant milestone in the partnership between Emory, Georgia Tech, and the University of Georgia, in that this is the first gift that was given to the Georgia Research Alliance specifically to be split between all three partner institutions to support joint projects,” said Johnna Temenoff, Petit Institute researcher and REM co-director from Georgia Tech.

“I believe this is reflective of our collective leadership in the field of regenerative medicine as a whole, and cell manufacturing in particular,” Temenoff added.

Since 2011, the REM has fostered the fundamental transformation of treatment options and outcomes for human disease and injuries through the development and translation of new technologies that boost the body’s ability to heal itself.

REM’s roots actually go back 30 years, to 1987 when Emory and Georgia Tech forged a historic alliance with creation of the Emory/Georgia Tech Biomedical Technology Research Center. That partnership evolved in 1998 with creation of the Georgia Tech/Emory Center or the Engineering of Living Tissues (GTEC, a National Science Foundation Engineering Research Center).

GTEC evolved to become REM, an Emory-Georgia Tech initiative until 2014, when UGA and its vaunted Regenerative Bioscience Center (RBC) joined.

“The purpose of these retreats has always been about getting people together from the three institutions to continue the discussion of how we can collaborate on our research,” says Steve Stice, the REM co-director from UGA, where he is a professor and director of the RBC, and a researcher with the Petit Institute for Bioengineering and Bioscience at Georgia Tech. “We’ve been doing this for some time now and some fantastic things that have come from it, and we expect more of that going forward.”

Participants in this year’s retreat also set out to demonstrate examples of commercial and academic success as a way to highlight the impact that traditional REM seed grants have had on fostering collaborative research and commercial translation across the state.

“We then tried to capture that momentum to establish more intra-institutional collaborations through interactions at the poster and speed dating sessions, and make next year’s grants even more successful,” Temenoff said.

Several accounts were shared from fledgling companies that either emerged from REM collaborations, or were assisted by REM interactions and grants, or exist within the realm of regenerative medicine in general. The companies – Sanguina, ArunA Biomedical, and Cambium Medical Technologies – represent the kind of success stories that REM, and its seed grants program, was built for. Since 2010 (a year before the actual launch of the REM center), the seed grants have resulted in nearly $18 million in leveraged funding (a return on investment of over 3:1).

In her presentation on the ‘academic path to success,’ Petit Institute researcher Susan Thomas emphasized the importance of the REM seed grant she and Emory researcher Ian Copland (who passed away suddenly in July 2015) received in 2014-2015. “That grant has helped us expand our research,” she said. “It opened up doors to new directions and additional funding and to new avenues that we’re still exploring.”

Representatives from each REM institution also had a chance to present their distinct SWOT (Strengths, Weaknesses, Opportunities, Threats) analyses before adjourning for a poster session featuring research from previous seed grant winners. Then they moved onto a ‘research speed dating’ networking session. (“Now is the time to practice your elevator speech,” quipped Stice, who wore a referee’s whistle around his neck and used it to move the conversations along).

That was followed by a ‘wrap session,’ to discuss the REM seed grants and how best to utilize those going forward. Seed grant applications for the coming year are due in July.

Ultimately, the goal is to keep the momentum going, and that may include expanding the partnership that currently comprises REM. Present for last month’s gathering were representatives from Augusta University (AU), including David Hess, dean of AU’s Medical College of Georgia.

“It’s great to see this become a broader group,” said Ned Waller, REM co-director from Emory. “The spirit of REM is to encourage collaboration, and a Georgia-wide initiative is to the benefit of everyone.”

REM Center

An assistant professor in the Georgia Tech School of Electrical and Computer Engineering (ECE) since 2014, Sarioglu leads the Biomedical Microsystems Laboratory. He will use his award to develop a radical lab-on-a-chip technology with integrated electronic readout to analyze heterogeneous cell populations. Lab-on-a-chip systems are microfluidic devices that analyze small volumes of biological samples in a compact-footprint, with minimal cost and with the ultimate goal of replacing centralized laboratories. However, lab-on-a-chip devices typically lack an on-chip readout mechanism, and therefore, require microscopy or other benchtop instruments for quantitative results, negating their cost and size advantages.

Sarioglu’s research combines two traditionally distant technical disciplines, microfluidics and telecommunications, to integrate a low-cost, scalable electronic sensor network into lab-on-a-chip devices. Specifically, he uses code-division multiplexing employed in CDMA telecommunication networks to develop a network of biosensors for quantitatively monitoring bioanalytical processes in a microfluidic device. Given the need for disposable, quantitative biomedical assays, Sarioglu's research, enabled by this award, will have wide-ranging applications from basic biology research to point-of-care diagnostics.



The Beckman Young Investigator (BYI) Program provides research support to the most promising young faculty members in the early stages of their academic careers in the chemical and life sciences, particularly to foster the invention of methods, instruments, and materials that will open up new avenues of research in science. Projects supported by the BYI program are truly innovative, high-risk, and show promise for contributing to significant advances in chemistry and the life sciences. They represent a departure from current research directions rather than an extension or expansion of existing programs. The 2017 BYI Awardees were selected from a pool of over 300 applicants after a three-part review led by a panel of scientific experts.

Kosal is an associate professor in the Sam Nunn School of International Affairs within Georgia Tech’s Ivan Allen College of Liberal Arts. Her research (which explores the relationships among technology, strategy, and governance) is focused on two areas that often intersect: reducing the threat of weapons of mass destruction, and understanding the role of emerging technologies for security.

The author of Nanotechnology for Chemical and Biological Defense, Kosal’s research considers the role nanotechnology, cognitive science, biotechnology, and converging sciences have on states, non-state actors, balance of power, deterrence postures, security doctrines, nonproliferation regimes, and programmatic choices.

Pokutta is the David M. McKenney Family Associate Professor in the Stewart School of Industrial & Systems Engineering, where his research has concentrated on combinatorial optimization and polyhedral combinatorics, with a particular focus on cutting-plane methods and extended formulations.

His industry research interests are in optimization and machine learning in the context of analytics with a focus on real-world applications, both in established industries as well as in emerging technologies. Pokutta is also director of the Interactive Optimization and Learning Lab and associate director of the Center for Machine Learning, both at Georgia Tech.

Rhee, who might be best known as the attending physician to U.S. Representative Gabrielle Giffords, as well as other victims, following the 2011 shootings in Tucson, Arizona, is chief of acute care surgery and medical director of the Marcus Trauma Center at Grady Memorial Hospital in Atlanta. Rhee served 24 years in the U.S. Navy, working as a battlefield casualty physician in Afghanistan and Iraq.

Among other things, Rhee was President Barack Obama’s guest at the 2011 State of the Union Address, designated surgeon for President Bill Clinton during a trip to China, and in 2001 was one of the first American military surgeons deployed in Afghanistan. His research interests include hemorrhagic shock, suspended animation for trauma, hemostatic agents, resuscitation immunology and formulation of resuscitation fluids, traumatic brain injury, transfusion and coagulopathy, trauma training, and advanced portable electronic medical devices.

Weinberg is a professor in Georgia Tech’s School of Music and the founding director of the Georgia Tech Center for Music Technology, where he leads the Robotic Musicianship group. A lifelong musician born in Israel, Weinberg developed a number of instruments for novices (such as the Beatbugs and the Squeezables) before conceiving the field of robotic musicianship.

His research focuses on developing artificial creativity and musical expression for robots and augmented humans. Among the projects he’s developed is a prosthetic robot arm for amputees that restores and enhances human drumming abilities.

These four researchers, from a diverse range of disciplines, were recently approved by the steering committee of the Petit Institute, whose roster of world-class researchers is more than 200 members.

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

New simulations of DNA as a transport conduit could shatter the way scientists have thought about how large molecules called transcription factors diffuse on their way to carry out genetic missions, according to a study by researchers at the Georgia Institute of Technology. The simulations add important brush strokes to our picture of elusive inner mechanics of cells.

The simulations strongly support the hypothesis that, in a live cell, DNA is in constant motion, making it the dominant mover of transcription factors, to their target sites on DNA. There, the factors regulate the transcription of genetic code into life-sustaining action.

DNA gorilla cage

How transcription factors travel through DNA has been a mystery, because the protein molecules are so large, and natural DNA is so tightly tangled. Spaces inside the windings are usually much smaller than the transcription factors that need to pass through them.

“If the thicket is so thick, and on top of that doesn’t move, then it should be impenetrable. So, how do you get stuff through to the right site?” asked Jeffrey Skolnick, a professor in Georgia Tech’s School of Biological Sciences.

If DNA were indeed immobile, the protein molecule would appear jammed into the DNA thicket like a gorilla into a dog cage.

DNA watch springs

But Skolnick and collaborator Edmond Chow, a computer scientist specializing in algorithms that tackle very large scientific questions, believe the widely held assumption that naturally occurring DNA is rigid like bars is false. Their simulations turn the bars into wires, tense like watch springs, that flex and rattle around with snake-like motions.

"The DNA motion is far and away the dominant force moving molecules through its thicket," Skolnick said. "DNA is a bully."

Skolnick, who directs Georgia Tech’s Center for the Study of Systems Biology, and Chow, an associate professor at Georgia Tech’s School of Computational Science and Engineering, published a paper on their simulations on June 6 in Biophysical Journal.

Chow and Skolnick modeled the simulation on a transcription factor called LacI moving through the DNA of an Escherichia coli bacterial cell. LacI is an inhibitory molecule that depends on lactose, but that function played no role in the study. The well-known transcription factor is a mainstay in many experimental studies on transcription factor movement.

Slide, hop, and hopscotch

In the simulations, DNA strands flex out of LacI’s path and also juggle the large molecule forward into the next pocket in the thicket, and so on.

Hypotheses based on rigid DNA would leave transcription factors moving more slowly than they actually appear to. But Chow and Skolnick’s wiggly simulations square with rates of diffusion established in lab experiments and explain why they’re so fast.

Transcription factors have been known to slide along DNA strands, like magnets down slippery wires, until they click into a specific groove where they fit perfectly, which is where they do their work. And they’ve been known to hop off the DNA strand and then reattach.

“But the sliding and hopping combined still don’t account for the speed of diffusion,” Chow said.

Reattaching after a hop can actually reduce the transcription factor’s speed through the DNA, by putting it back on a place on the strand where it’s been before. The simulated wobble of the DNA thicket flicks transcribers to make them hopscotch more and farther, increasing their speed of diffusion.

Herculean computations

The simulations will aid other researchers’ understanding of important cell processes and potentially help boost speed and accuracy in biological and medical research. The computation behind the simulated dynamics was herculean.

“These simulations are unique to this problem because of their enormity and the advanced computing techniques used. Very efficient algorithms ran in parallel on powerful computers, and, still, it took three weeks for the simulations to complete,” Chow said.

Parallel computing chops a problem into pieces that can be run simultaneously, or in parallel, instead of in one long, time-consuming process. This allows programs to exploit many processors at the same time, multiplying the speed of computation.

Even with that power, to make the simulation computable at all, the researchers had to slim down the model of the DNA and LacI to reveal motion dynamics without dressing up all the details of cellular DNA. “You have to choose which parts you ignore and which parts you put in,” Skolnick said. “If you put everything in, you can’t do it, even with the fastest codes.”

Cellular toy land

The researchers want to take on much tougher challenges that could, years from now, lead to a toy-like, simplified model of a complete cell.

“The ultimate goal is to put a whole cell on a computer. Let it live. Let it divide, and understand the processes,” Skolnick said. “Maybe even let the cell mutate and evolve.”

The computer science behind that would be aspirational. “When the size of a problem grows, the computing costs to solve it can grow disproportionately,” Chow said. “You have to build algorithms that can run efficiently even when you scale up the problem size.”

Also read: Instruction Manual to Repair DNA

Also read: Did RNA evolve in puddles?

Also read: Was the Secret Spice in Primal Gene Soup a Thickener?

This research was supported by the National Science Foundation (grant ACI-1147843). Tadashi Ando from the Tokyo University of Science contributed insights that aided in this research. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsoring agencies.

Radiation and chemotherapy can cause a DNA double-strand break, one of the most harmful types of DNA damage. The process of homologous recombination — which involves the exchange of genetic information between two DNA molecules — plays an important role in DNA repair, but certain gene mutations can destabilize a genome. For example, mutations in the tumor suppressor BRCA2, which is involved in DNA repair by homologous recombination, can cause the deadliest form of breast and ovarian cancer. 

Alexander Mazin, a professor at Drexel University’s College of Medicine, and Francesca Storici, an associate professor at Georgia Tech’s School of Biological Sciences, have dedicated their research to studying mechanisms and proteins that promote DNA repair. 

In 2014, Storici and Mazin made a major breakthrough when they discovered that RNA can serve as a template for the repair of a DNA double-strand break in budding yeast, and Rad52, a member of the homologous recombination pathway, is an important player in that process. 

“We provided evidence that RNA can be used as a donor template to repair DNA and that the protein Rad52 is involved in the process,” said Mazin. “But we did not know exactly how the protein is involved.”

In their current study, the research team uncovered the unusual, important role of Rad52: It promotes “inverse strand exchange” between double-stranded DNA and RNA, meaning that the protein has a novel ability to bring together homologous DNA and RNA molecules. In this RNA-DNA hybrid, RNA can then be used as a template for accurate DNA repair. 

It appeared that this ability of Rad52 is unique in eukaryotes, as otherwise similar proteins do not possess it. 

“Strikingly, such inverse strand exchange activity of Rad52 with RNA does not require extensive processing of the broken DNA ends, suggesting that RNA-templated repair could be a relatively fast mechanism to seal breaks in DNA,” Storici said. 

As a next step, the researchers hope to explore the role of Rad52 in human cells. 

“DNA breaks play a role in many degenerative diseases of humans, including cancer,” Storici added. “We need to understand how cells keep their genomes stable. These findings help bring us closer to a detailed understanding of the complex DNA repair mechanisms.”

The research was supported by the National Institutes of Health, the National Science Foundation and the Howard Hughes Medical Institute.

These results offer a new perspective on the multifaceted relationship between RNA, DNA and genome stability. They also may help to identify new therapeutic targets for cancer treatment. It is known that active Rad52 is required for proliferation of BRCA-deficient breast cancer cells. Targeting this protein with small molecule inhibitors is a promising anticancer strategy.  However, the critical activity of Rad52 required for cancer proliferation is currently unknown.

This new Rad52 activity in DNA repair, discovered by Mazin, Storici and their team, may represent this critical protein activity that can be targeted with inhibitors to develop more specific — and less toxic — anti-cancer drugs. Understanding of the mechanisms of RNA-directed DNA repair may also lead to development of new RNA-based mechanisms of genome engineering. 

This research was supported by the National Institute of General Medical Sciences (NIGMS) of the NIH (grant GM115927), the National Science Foundation (grant 1615335), and the Howard Hughes Medical Institute Faculty Scholar Program (grant 55108574). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsoring agencies.

Written by Drexel University.

CITATION: Olga M. Mazina, Havva Keskin, Kritika Hanamshet, Francesca Storici,
Alexander V. Mazin, “Rad52 Inverse Strand Exchange Drives RNA Templated
DNA Double-Strand Break Repair,” (Molecular Cell, 2017). http://dx.doi.org/10.1016/j.molcel.2017.05.019

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Media Relations Contacts: Georgia Tech – John Toon (404-894-6986) (jtoon@gatech.edu) or Ben Brumfield (404-385-1933) (ben.brumfield@comm.gatech.edu) or Drexel University -- Lauren Ingeno, (215-895-2614) (lmi28@drexel.edu).

As the annual honoree, Platt was selected for his outstanding contributions to improving gender and racial diversity in his field.

As part of the award, he will have the opportunity to give a lecture offering his vision of the challenges and opportunities of greater diversity in biomedical engineering at the BMES Annual Meeting in Phoenix. His lecture will also be published in The Annals of Biomedical Engineering.

Platt is the Diversity Director for the NSF Center on Emergent Behaviors of Integrated Cellular Systems, and he is a co-founder and co-director of Project ENGAGES, a biotechnology and engineering research program for African-American high school students in Georgia Tech laboratories. He was also featured in the Diverse: Issues in Higher Education magazine in 2015 as an Emerging Scholar.

Platt’s research focuses on understanding how cells sense, respond, and remodel their immediate environments for repair and regeneration in health and disease, and translating this knowledge into addressing global health disparities.

BMES is an international society that aims to build the biomedical engineering community and support the professionals who develop and use engineering and technology to advance human health and well-being.

By Polly Ouellette

View highlights of Manu Platt's presentation at BMES in Phoenix, Oct 2017.

Full video of Manu Platt's presentation.

Researchers know that much. The problem is, underlying causes of memory problems in Alzheimer’s disease are still poorly understood.