Outstanding Paper
 Jordan Ciciliano, a trainee in Dr. Lam's lab.

“Resolving the multifaceted mechanisms of the ferric chloride thrombosis model using an interdisciplinary microfluidic approach” recently published in Blood (Impact Factor: 10.452)

 
Outstanding Thesis
Adrian Lam, PhD , who was a member of Dr. Oshinski’s lab, until his graduation in Fall 2015.

“Development of a combined angiography and late Gadolinium enhancement MRI sequence”

Outstanding Advisor
Krishnendu Roy, PhD  
 
The awards were presented at the BioE recruitment event on March 11th.
Please join us in congratulating the winners and we look forward to hearing from Jordan Ciciliano and Dr. Roy on BioE Day, May 12th. 
Please note that the Christopher Ruffin Award will be announced at BioE Day as well.

“I’m starting to realize that maybe I want something different and the idea of entrepreneurship is really attractive,” says Nelson. “Making something based on your research, and looking back to say it succeeded or failed – that kind of independence appeals to me.”

Nelson recently got a substantial boost for his research efforts when he was named an American Heart Association (AHA) Fellowship Award winner. The award began January 1 and will extend through 2017.

AHA is supporting Nelson’s project, titled ‘The effects of diet induced obesity on lymphatic function and therapeutic intervention in lymphedema progression,’ with an award totaled at $52,000 over two years.

“Lymphedema affects about one in six cancer survivors,” says Nelson, who works in the lab of J. Brandon Dixon, faculty member of the Petit Institute for Bioengineering and Bioscience. “It basically occurs as the result of some common cancer treatments, like lymph node removal, chemotherapy, radiation.”

The disease causes irreversible swelling, mostly in the arms or legs. It results from a blockage in the lymphatic system (part of your immune system). This blockage prevents lymph fluid from draining well and that fluid buildup leads to swelling. There is presently no cure, but lymphedema can be managed with early diagnosis.

“It turns out that people who are obese develop lymphedema at a much higher rate than the rest of the population,” Nelson says. “We want to understand how obesity affects the lymphatic system and its function.”

Nelson, who is from the Nashville, Tennessee, area, earned his undergraduate degree in mechanical engineering at Mississippi State. After enrolling at the Georgia Institute of Technology, he joined Dixon’s Laboratory of Lymphatic Biology and Bioengineering (LLBB), where researchers focus on developing non-invasive methods to quantify lymphatic function.

He’s always been interested in pursuing a career in industry once he earns his PhD. But since arriving at Georgia Tech, is thoughts on what that might look like have shifted a little bit. 

“Now, I’m thinking that I’d really like to start up a small company, or work with an early-stage company,” he says.

That line of thought is driven in part by his experience in the TI:GER (Technological Innovation: Generating Economic Results) program, administered through the Scheller College of Business at Tech. The program is designed to teach students how to address the multidisciplinary issues that are part of technology commercialization. 

Through TI:GER, Nelson has teamed with two MBA students and two Emory Law students. Together, they’re focused on the commercialization of diagnostic and monitoring devices for lymphedema. 

The team, called Lumenostics, is working on a product designed to detect swelling in the earliest stages of the disease. This semester, the students will be engaged in business plan competitions.

“The training I’ve gotten through TI:GER is irreplaceable,” Nelson says. “It really sets you apart and gives you great exposure to the business side of research.”

CONTACT:

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

García, who works in the lab of Petit Institute researcher Andrés García (no relation), has been honored with a 2016 Society for Biomaterials Student Award for Outstanding Research.

The Society for Biomaterials (SFB), which promotes advances in biomedical research and development, annually recognizes significant contributions to the field of biomaterials science from industry, academia, regulatory agencies and students. 

The 2016 awards and respective recipients include: 

• Founders Award: Cato Laurencin, MD, PhD (University of Connecticut)

• Clemson Award for Applied Research: Justin Hanes, PhD (The Johns Hopkins University School of Medicine) 

• Clemson Award for Basic Research: Molly Stevens, PhD (Imperial College of London)

• Clemson Award for Contributions to the Literature: Rocky Tuan, PhD (University of Pittsburgh)

• C. William Hall Award: Jim Curtis, PhD (Dow Corning Corporation)

• SFB Award for Service: Alan Litsky, MD, ScD (Ohio State University)

• Technology, Innovation and Development Award: Joseph Salamone, PhD (Rochal Industries LL)

• Young Investigators Award: Fan Yang, PhD (Stanford University)

• Student Awards for Outstanding Research: Jose García (Georgia Institute of Technology)

• Student Awards for Outstanding Research: Abigail Erin Loneker (University of Pittsburgh)

• Student Awards for Outstanding Research: Veronica Ibarra (Illinois Institute of Technology)

“Every year we recognize our members for their outstanding achievements in the biomaterials industry, whether it be from industry, academia, regulatory agencies or from the student population,” said Tom Webster, SFB president. “The 2016 recipients have shown tremendous thought leadership in their respective fields. I commend each and every one of them on this achievement and look forward to their continued contributions to our industry and Society.” 

García is a trainee in the Integrative Graduate Education and Research Traineeship (IGERT) program in Stem Cell Manufacturing, awarded to Georgia Tech in 2010 to educate and train the first generation of Ph.D. students in the transition and commercialization of stem cell technologies for diagnostic and therapeutic applications. He earned his Bachelor of Science degree in biological engineering with a concentration in biomechanics from the University of Florida in May 2012.

The recipients are honored for their contributions to advancing the Society’s objectives and goals in a variety of ways and will be honored during the 2016 World Biomaterials Congress, May 18, 2016, Montreal, Canada.

CONTACT:

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

CONTACT:

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

CONTACT:

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

Outstanding Paper
He Zheng, a trainee in Dr. Stanley’s lab.
Paper Title, “The Adaptive Trade-Off between Detection and Discrimination in Cortical Representations and Behavior” and was published in Neuron (a division of CELL) in January of 2014.
 
Outstanding Thesis
Andrew Siefert, PhD , who was a member of Dr. Yoganathan’s lab, until his graduation in Spring 2014.
Thesis Title: “Mitral Valve Force Balance: A Quantitative Assessment of Annular and Subvalvular Forces”
 
Outstanding Advisor
J. Brandon Dixon, PhD (Mechanical Engineering)
 
The awards will be presented at the BioE recruitment event on March 27th.
Please join us in congratulating the winners and we look forward to hearing from He Zheng and Dr. Dixon on BioE Day, April 30th.
Please note that the Christopher Ruffin Award will be announced at BioE Day as well.

Outstanding BioE Student Paper

• All BioE students are eligible - Must be currently enrolled
• $750 cash and plaque award
• Nominated by Advisor - nominations must include a letter of support from advisor discussing impact and significance of the work
• Electronic copy of paper must accompany nomination
• Paper must be published, in press or accepted in the time frame January 1 - December 31, 2014

Outstanding BioE PhD Thesis

• All BioE students are eligible - Do not have to be currently enrolled 
• $750 cash and plaque award
• Nominated by Advisor
• Nominations must include a letter of support from advisor
• Electronic copy of Ph.D. thesis must accompany nomination
• Thesis Certificate of Completion form must be signed by ALL committee members in the time frame January 1 - December 31, 2014

Outstanding BioE Advisor

• All BioE Program Faculty are eligible
• $500 discretionary funds and plaque
• Nominated by graduate student(s) – Submit a letter explaining why you are nominating a faculty member. 

Christopher Ruffin Leadership Award

The Student Leadership Award was established to honor the memory of Christopher Ruffin and his exceptional contributions to the BioE Program. Chris began working at GT in 1994 and joined the bioengineering community in April 2001. As Academic Advisor in the BioE Program, Chris worked tirelessly to support the BioE students and faculty.  This award recognizes a current graduate student for his or her superior contributions to the BioEngineering Program. The Leadership Award will be awarded to a student whose influence, ideals and activities throughout his/her time in the BioEngineering Program has left a long lasting and positive impression on the institution and has raised the standard of excellence for future BioEngineering classes. Examples of strong leadership qualities include activities such as peer mentoring, teaching, and service.

Nominations should be submitted to Laura Paige with the BioE program. Nominations for the Outstanding Awards will be reviewed by the BioE Faculty Advisory Committee and nominations for the Ruffin Leadership Award will be reviewed by a BGA committee. Winners will be announced at the BioE Reception on March 27, 2015 (Recruitment Day).

“He had 100-plus students to work with, but he treated all of us like we were individuals, really went above and beyond to make sure everything went smoothly for every student who came in,” says Pacheco, inaugural winner of the Chris Ruffin Graduate Leadership Award, announced at BioE Day.

Pacheco is a fifth year Ph.D. student in Todd Sulchek's lab, has a string of honors and awards behind her, including: an NSF Graduate Research Fellowship, Goizueta Foundation Fellowship, NIH-Georgia Tech Biomaterials Training Grant, and the Georgia Institute of Technology Presidential Fellowship.

She’s also been a busy participant in the Graduate Leadership Program, which gets to the heart of the Ruffin Award. Among other things, she’s served as Education and Outreach co-chair for the Bioengineering and Bioscience Unified Graduate Students (BBUGS), ambassador and interim vice president of the Georgia Tech Salsa Club, been a mentor to other students, and has been active on the Bioengineering Graduate Student Advisory Committee (BGSAC) and the Latino Organization of Graduate Students.

So basically, she does Ruffin’s legacy proud, according to Robert Butera, bioengineering professor and former program director for BioE (2005-2008), who says, “it’s totally appropriate to name a graduate student leadership award after Chris, because he wasn’t just a staff person, he was a leader. Running the BioE program is an important task, with a lot of moving parts, and it required him to interface with all the participating schools and their own rules and cultures. He made it look effortless and easy.”

The Ruffin Award, like BioE Day, was invented and defined by students in the BioE community. “They made the nominations, set the criteria,” says Butera, who was asked at the last minute to be the award presented, and notes that Pacheco “played a critical role in motivating other students and pitching in to volunteer and help lead student organizations.”

Andrés García, current BioE program director, was approached in the spring by students who wanted to create a special day focused on the BioE community, before anyone really was sure what shape it would take. Grad students Jessica Butts and Katie Hammersmith, the BioE co-chairs, originally figured on a program that would last a couple of hours, but as the idea developed, “we realized we had enough programming to make it a whole day,” says Hammersmith.

The morning began with rapid-fire presentations by students (Ph.D. student Jenna Wilson, from Todd McDevitt's lab and an NSF-IGERT Stem Cell Biomanufacturing Trainee and GAANN Fellow, won this award). The poster presentation contest was won by Ph.D. students Tom Bongiorno (Todd Sulchek's lab) and Lauren Priddy (Bob Guldberg's lab). Bongiorno, also an NSF-IGERT Stem Cell Biomanufacturing Trainee, also won the award for outstanding paper. Jonathan Newman (Steve Potter's lab), who earned his Ph.D. in 2013, won the outstanding thesis award. Julie Champion, an assistant professor in the School of Chemical and Biomolecular Engineering and a member of the Parker H. Petit Institute for Bioengineering and Biosciences, was named outstanding advisor.

“Since it was the first year, we weren't sure what to expect for the turnout, but it ended up being very well attended. We are really looking forward to the event growing in future years,” Hammersmith says. “We were impressed with the attendance by programs outside of Petit Institute who came to inform students about the many opportunities to enrich their graduate education as well as the high-quality presentations by students.”

There was a cookout, there were games, the highlight being the faculty-student water balloon toss – the winners were assistant professor J. Brandon Dixon and grad student Josh Hooks, i.e., they were the last team standing (dry). But a major unifying theme to the first BioE Day had to be the Ruffin Award

“I knew Chris, knew him really well, and what kind a person he was,” Pacheco says. “So, I’m very honored.”

“This is the best model for interdisciplinary research, a program that spans multiple schools and departments, with faculty participating from multiple colleges at Georgia Tech and Emory,” explains Andrés García, Regents’ Professor in the George W. Woodruff School of Mechanical Engineering, and program director for BioE. “The goal is to integrate engineering with life science and everything rotates around that. So, as you can imagine, we have some outstanding students, remarkable young people with great ideas. But when they came to me earlier this year and said, ‘we’d like to have a BioE Day,’ I was like, ‘what’s that?’”

It’s an opportunity to build community, to bring together the 100 or so grad students from disparate backgrounds and pathways, and honor their work, in one place on one day, which is this Monday, May 12, when the first BioE Day takes place in the Parker H. Petit Institute for BioEngineering and Bioscience (11 a.m. to 6 p.m.).

As you might expect from an interdisciplinary program, the idea took shape out of a collective thought process.

“Someone suggested we have something called BioE Day, and the reaction was, ‘sounds great … what do you mean?’ So we took some time to define what we wanted that to be,” says Tom Bongiorno, a third-year Ph.D. student and president of the BioEngineering Graduate Student Advisory Committee.

“So we talked a lot about BioE identity. We come from up to eight home schools, so we don’t all take classes together. This seemed like a good idea, a way to build or improve our identity.”

They’ll now use BioE Day as the venue to announce BioE’s annual awards, but the graduate students have even given that a new twist. This year, they’ve replaced the “best” appellation with “outstanding.” 

“’Best’ seemed kind of arrogant and a little intimidating,” says Bongiorno, who will be honored as the BioE Outstanding Paper winner and offer a presentation about his paper at the event.

Several other awards will be given out, including Outstanding Thesis (Jonathan Newman, who earned his Ph.D. in 2013) and Outstanding Advisor (Julie Champion, assistant professor in the School of Chemical and Biomolecular Engineering). This will also mark the first year of the Chris Ruffin Graduate Student Leadership Award, which honors the memory of the former longtime BioE academic advisor.

“Chris was a tireless champion for the BioE Program. He truly cared about the students and faculty, was a fantastic listener, and problem solver,” says García, who will make the announcement Monday afternoon. “He contributed significantly to the success of BioE.”

There will be, among other things, speeches by the award winners, rapid-fire research presentations from students, a poster presentation, a senior graduate student panel discussion, a cookout at the end of the day, and plenty of games (including a faculty water balloon toss competition).

“This all about community building,” Bongiorno says. “It’s a way to make everyone a little more visible to everyone else.”

View the agenda and register here. 

Award Winners

Julie Champion, Outstanding Advisor

Champion is an assistant professor in the School of Chemical and Biomolecular Engineering and a member of the Parker H. Petit Institute for Bioengineering and Biosciences. She earned her B.S.E. in Chemical Engineering from the University of Michigan in 2001 and completed her Ph.D. in Chemical Engineering at the University of California – Santa Barbara, in 2007, as a National Science Foundation graduate fellow. She was a National Institutes of Health postdoctoral fellow from 2007-2009 at the California Institute of Technology. Champion’s current research focuses on design and self-assembly of therapeutic nanomaterials made from engineered proteins for applications in cancer and immunology. She has received a BRIGE award from the National Science Foundation and the Georgia Tech Women in Engineering Faculty Award for Excellence in Teaching.

Tom Bongiorno, Outstanding Paper

Bongiorno is a third year Ph.D. candidate in BioEngineering. He received a B.S. in Mechanical Engineering in 2011 from the University of Notre Dame, where he worked on a stem cell-based tissue-engineering project. As an undergraduate, Bongiorno conducted a summer research project on microparticle phagocytosis in the lab of Todd Sulchek, where he has returned for his graduate work. Bongiorno is seeking to use the mechanical properties of individual cells as bases for identifying and sorting differentiating stem cells. The goal of his research is to use microfluidic technology that sorts cells based on their mechanical properties to obtain a purified population of a desired cell phenotype. Bongiorno is a Georgia Tech President's Fellow and was a trainee on the stem cell biomanufacturing IGERT at Georgia Tech from 2011-2013. His winning paper is titled, “Mechanical stiffness as an improved single-cell indicator of osteoblastic human mesenchymal stem cell differentiation.”

Jonathan Newman, Outstanding Thesis

Newman completed his undergraduate studies at the State University of New York (SUNY) – Binghamton in 2007, majoring in BioEngineering. He attended the Georgia Institute of Technology for his graduate studies under the mentorship of Steve Potter, earning his PhD in 2013 (his thesis work was supported by a National Science Foundation IGERT Fellowship and a National Science Foundation Graduate Research Fellowship). He is now a postdoctoral associate in the laboratory of Matt Wilson at MIT, leveraging the skills he gained during his thesis work at Georgia Tech in order to understand the neural basis of memory consolidation in freely moving rodents.

Optogenetics is a set of technologies that enable optically triggered gain or loss of function in genetically specified populations of cells. Optogenetic methods have revolutionized experimental neuroscience by allowing precise excitation or inhibition of firing in specific neuronal populations embedded within complex, heterogeneous tissue. During his thesis work at Georgia Tech, Newman developed a feedback control technology that automatically adjusts optical stimulation in real-time to precisely control neuronal network activity levels. This technique (called the ‘optoclamp’ in Steve Potter's lab) allows extremely robust and precise control of network firing levels, far surpassing the abilities of existing technologies. Ming-fai Fong and Pete Wenner from Emory University have subsequently used the optoclamp to show conclusively that reductions in excitatory neurotransmission directly trigger homeostatic increases in synaptic strength, independent of changes in firing activity. These results oppose a large body of literature on the subject and have significant implications for memory formation and maintenance in the central nervous system. 

“We have incredible clinicians at Emory, brilliant engineers at Tech, and tremendous entrepreneurial resources through VentureLab, the Advanced Technology Development Center, and FlashPoint,” said Erik Reinertsen, an M.D./Ph.D. student at Emory and Tech and managing director of Forge. “Atlanta will be a leader in this space.”

Forge builds on a history of productive collaborations between clinicians and engineers in Atlanta, but with a human-centric focus.

“It’s driven by the graduate and medical students,” said Yogi Patel, a Ph.D. student in bioengineering. “We focus on startups, people, and learning through doing. Our colleagues in Silicon Valley and Boston have helped us understand that people are more important than specific technologies.”

Forge aspires to bring other lessons learned from those colleagues into the Atlanta medical community.

“We hope to instill elements of the Silicon Valley culture into medicine: big vision, pay-it-forward mentorship, and a get-it-done attitude,” said Evan McClure, an Emory M.D./MBA student and Forge director of finance and operations.

Forge has already hosted pitch nights, workshops, and networking events, and is planning its first Healthcare Hackathon for the fall, all with the aim of connecting innovators and clinicians to existing resources.

“Healthcare innovation in Atlanta is growing quickly, but suffers from fragmentation,” said Reinertsen.

Though graduate students and entrepreneurs are spearheading Forge — under the guidance of academic leadership from Emory and Tech — undergraduates, faculty, postdoctoral scholars, residents, and fellows are encouraged to participate.

Forge is looking for work spaces on both the Tech and Emory campuses. More information is available at forgeatl.com.

 Nomination letters from students, faculty or staff describing the nominee’s contributions should be submitted to the Laura Paige in the BioE office (laura.paige@bioengineering.gatech.edu) by COB April 18. Nominations will be evaluated by a selected group of BioE students and staff. This award also carries a monetary prize.

“That’s the beauty of this class, not only is the topic of stem cell engineering unique, but thanks to video conferencing technology, Georgia Tech students can now take a class with their peers from across the country,” said McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering.

Stem Cell Engineering (BMED 8813) has been offered since the spring of 2011 and was created by McDevitt as a way to educate graduate students about a research area that is becoming increasingly popular.

Including the 10 students at Tech, there are 39 students enrolled in this semester’s course. Aside from Tech, they are located at Washington University, the Massachusetts Institute of Technology, Boston University, University of California, Merced, and the University of Wisconsin. And although this is a graduate-level course, undergraduates can take the course with McDevitt’s permission.

So what can students expect during a week of classes? On Tuesdays, students from all of the participating campuses hear a lecture via the video conferencing system on a stem cell engineering topic — think everything from stem cell biology basics to stem cell biomanufacturing.

When the class meets on Thursdays, two students (at each location) typically lead a 50-minute discussion on a recently published journal article related to the lecture topic to their in-person peers.

Then, for the remainder of class, the Tech group video conferences with the students at other locations to discuss the key points brought up by each local group.

“It’s very helpful to have the perspective of students and faculty from other universities,”  said Jenna Wilson, a Ph.D. student in the bioengineering program who is a former student of the course turned teaching assistant. “Because people at other universities have different areas of research expertise, they can provide greater insight into aspects of the stem cell engineering field and pose interesting questions for discussion.”

Wilson also appreciated the small class size and discussion format of the course.

“Both aspects allow for great conversations with other students and some of the leading faculty in the stem cell engineering field,” she added. “Even though the class is broadcast across six universities, it's still a small group where you can feel comfortable sharing ideas and opinions.”

The course is typically offered during spring semester. For more information, email McDevitt .

The Institute’s College of Engineering ranked No. 6 and all 11 of the programs within the college are ranked in the top 10, including industrial engineering (No. 1), biomedical and bioengineering (No. 2), environmental (No. 4), civil (No. 5), aerospace (No. 5), mechanical (No. 5), electrical (No. 6), computer (No. 7), nuclear (No. 8), materials (No. 9) and chemical (No. 10). Georgia Tech appears on the top 10 list of engineering specialties more than any other ranked institution.

"Georgia Tech's strong rankings with U.S. News & World Report year after year reflect the Institute's ongoing commitment to excellence in research and teaching, as well as a legacy of preparing innovators and leaders," said Georgia Tech President G.P. "Bud" Peterson.

The Institute tied for the No. 9 spot in overall computer science rankings, coming in No. 6 in both systems and artificial intelligence and No. 8 in theory.

Georgia Tech moved from No. 26 to No. 24 in overall chemistry rankings and up to No. 29 in overall physics rankings. In discrete mathematics and combinatorics, the Institute moved up four spots to No. 4.

The Scheller College of Business full-time MBA program ranked No. 27, while the Institute’s part-time MBA program ranked No. 20, moving up from the No. 24 spot in 2014.

Arrays of the tweezers could be combined to study multiple molecules and cells simultaneously, providing a high-throughput capability for assessing the effects of mechanical forces on a broad scale. Details of the devices, which were developed by researchers at the Georgia Institute of Technology and Emory University in Atlanta, were published February 19, 2014, in the journal Technology.

“Our lab has been very interested in mechanical-chemical switches in the extracellular matrix, but we currently have a difficult time interrogating these mechanisms and discovering how they work in vivo,” said Thomas Barker, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “This device could help biologists and biomedical engineers answer questions that cannot be answered right now.”

For example, a cell that’s binding the extracellular matrix may bind with one receptor while the matrix is being stretched, and a different receptor when it’s not under stress. Those binding differences could drive changes in cell phenotype and affect processes such as cell differentiation. But they are now difficult to study.

“Having a device like this will allow us to interrogate what the specific binding sites are and what the specific binding triggers are,” Barker explained. “Right now, we know very little about this area when it comes to protein biochemistry.”

Scientists have been able to study how single cells or proteins are affected by mechanical forces, but their activity can vary considerably from cell-to-cell and among molecules. The new tweezers, which are built using nanolithography, can facilitate studying thousands or more cells and proteins in aggregate. The researchers are currently testing prototype 15 by 15 arrays which they believe could be scaled up.

“For me, it’s not sufficient to pull and hold onto a single protein,” said Barker. “I have to pull and hold onto tens of thousands of proteins to really use the technologies we have to develop molecular probes.”

At the center of the tweezers are 2.8- micron polystyrene microbeads that contain superparamagnetic nanoparticles. The tiny beads are engineered to adhere to a sample being studied. That sample is attached to a bead on one side, and to a magnetic pad on the other. The magnet draws the bead toward it, while an electrophoretic force created by current flowing through a gold wiring pattern pushes the bead away.

“The device simultaneously pushes and pulls on the same particle,” Barker explained. “This allows us to hold the sample at a very specific position above the magnet.”

Because the forces can be varied, the tweezers can be used to study structures of widely different size scales, from protein molecules to cells – a size difference of approximately a thousand times, noted Wilbur Lam, an assistant professor in the Coulter Department. Absolute forces in the nano-Newton range applied by the two sources overcome the much smaller effects of Brownian motion and thermal energy, allowing the tweezers to hold the cells or molecules without constant adjustment.

“We are basically leveraging microchip technology that has been developed by electrical and mechanical engineers,” Lam noted. “We are able to leverage these very tiny features that enable us to create a very sharp electrical field on one end against an opposing short magnetic field. Because there are two ways of controlling it, we have tight resolution and can get to many different scales.”

As a proof of principle for the system, the researchers demonstrated its ability to distinguish between antigen binding to loaded magnetic beads coated with different antibodies. When a sufficient upward force is applied, non-specific antibody coated beads are displaced from the antigen-coated device surface, while beads coated with the specific antibody are more strongly attracted to the surface and retained on it.

Barker and Lam began working together on the tweezers three years ago when they realized they had similar interests in studying the effects of mechanical action on different biological systems.

“We shouldn’t be surprised that biology can be dictated by physical parameters,” Lam explained. “Everything has to obey the laws of physics, and mechanics gets to the heart of that.”

Lam’s interest is at the cellular scale, specifically in blood cells.

“Blood cells also respond differently, biologically, when you squeeze them and when you stretch them,” he said. “For instance, we have learned that mechanics has a lot to do with atherosclerosis, but the systems we currently have for studying this mechanism can only look at single-cell events. If you can look at many cells at once, you get a much better statistical view of what’s happening.”

Barker’s interests, however, are at the molecular level.

“We are primarily interested in evolving antibodies that are capable of distinguishing different force-mediated conformations of proteins,” he explained. “We have a specific protein that we are interested in, but this technique could be applied to any proteins that are suspected to have these force-activated changes in their biochemical activity.”

While the tweezers meet the specific experimental needs of Lam and Barker, the researchers hope to find other applications. The tweezers were developed in collaboration with graduate student Lizhi Cao and post-doctoral fellow Zhengchun Peng.

“Because of the scale we are able to examine – both molecular and cellular – I think this will have a lot of applications both in protein molecular engineering and biotechnology,” Lam said. “This could be a useful way for people to screen relevant molecules because there currently aren’t good ways to do that.”

Beyond biological systems, the device could be used in materials development, microelectronics and even sensing.

“This ability to detect discrete binding and unbinding events between molecular species is of high interest right now,” Barker added. “Biosensor applications come out of this naturally.”

CITATION: Lizhi Cao, et al., “A combined magnetophoresis/dielectrophoresis based microbead array as a high-throughput biomolecular tweezers,” (Technology 2014). http://dx.doi.org/10.1142/S2339547814500058

Research News
Georgia Institute of Technology
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Media Relations Contacts: John Toon (404-894-6986) (jtoon@gatech.edu) or Brett Israel (404-385-1933) (brett.israel@comm.gatech.edu).
Writer: John Toon

A new study found that neural circuits in the brain rapidly multitask between detecting and discriminating sensory input, such as headlights in the distance. That’s different from how electronic circuits work, where one circuit performs a very specific task. The brain, the study found, is wired in way that allows a single pathway to perform multiple tasks.

“We showed that circuits in the brain change or adapt from situations when you need to detect something versus when you need to discriminate fine details,” said Garrett Stanley, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, whose lab performed the research. “One of the things the brain is good at is doing multiple things. Engineers have trouble with that.”

The research findings were published online in the journal NEURON on March 5. The research was funded by the National Institutes of Health (NIH) and the National Science Foundation (NSF).

“Every day we are bombarded with sensations and the brain automatically chooses which ones to detect. This study may help scientists answer fundamental questions about how neurological disorders may disrupt the brain circuits that make those choices,” said Jim Gnadt, Ph.D., program director at the National Institute of Neurological Disorders and Stroke, part of NIH. “Insights into sensory perception may help design new therapies, including prosthetic devices for amputees that recreate human touch.”

The distance at which a person can discern two headlights from a single light is controlled by the acuity of the body’s sensory pathway. For decades neuroscientists have assumed that the level of one’s acuity is controlled by the distance between areas in the brain that are triggered by the sensory input. If these two areas of the brain closely overlap, then two sensory inputs — two headlights in the distance — will appear as one, the thinking went. The new study, for the first time, used animal models and optical imaging to directly assess how acuity is controlled in the brain, and how acuity can adapt to the task at hand. One neuronal circuit can do different things and do them in a robust way, the study found.

“The general problem that is not well understood is how information about the outside world makes its way into our brain, into these patterns of electrical activity that ultimately let us perceive the outside world,” Stanley said. “This paper squarely goes after that link between what the brain is doing, how it’s activated and what that means for perception.”

Sensory information is encoded in the brain, much like gene sequences in DNA code for some physical representation. The brain has corresponding codes for when the visual pathway detects an object, like a coffee cup. There’s a representation in the brain to transform that input into sensation.

Researchers had yet to adequately quantify the link between discerning whether an object exists and discriminating finer details about what that object is, Stanley said.

“Surprisingly, we don’t understand neural coding problems very well, either in normal physiology or in disease states,” Stanley said. “I think it’s great to be an engineer that works on this because engineers tend to love and think about very complicated systems.”

To learn about the details of the brain’s acuity, the researchers studied an animal with a high level of acuity — the rat. Rats are nocturnal animals that use their whiskers to sense the outside world. Their whiskers are arranged in rows, and chunks of brain tissue correspond to those individual whiskers. That’s similar to how a human’s body surface is mapped onto the brain surface. When a rat’s whisker touches something, a specific part of the brain becomes activated. When a person’s finger touches something, a specific part of the brain becomes activated.

“When we image the brain, we can move a whisker on the side of the face and on the opposite side of the brain there’s a little hotspot that you can image in real time,” Stanley said.
The researchers deflected rats’ whiskers and then used optical imaging technology to observe the areas of the brain that were activated and measured the overlap between those areas. Rats were also trained to perform a specific task depending on which whisker was deflected.

The researchers found that pathways in the brain have the ability to switch between doing different kinds of tasks, such as detecting a sensory input and deciding what to do with that information.

“Same circuit, same cells, but doing something different in two different contexts,” Stanley said.

When engineers want a circuit to do something, they build a circuit specific for that task. When they want a circuit to do something else, they build a different circuit. But in the brain, a pathway adaptively changes between being good at detecting something to being good at discriminating something, the study showed.

“As an engineer, I can’t design a circuit that would do that,” Stanley said. “This is where the brain jumps out and says, ‘I’m better than you are at this.’”

Learning more about how circuits in the brain multitask could lead to a better understanding of disease, therapeutic applications or to potentially improving how the brain functions. Stanley said that down the road engineers might be able to experimentally manipulate brain circuits to perform a desired task.

“Can we make individuals better at doing something? Can we have them detect things more rapidly or discriminate between things with better acuity?” Stanley said. “Using modern techniques, we believe that we can actually influence the circuit and have it selectively grab one kind of information from the outside world versus another.”

This research is supported by the National Institutes of Health (NIH) under award number R01NS48285, and by the National Science Foundation (NSF) Collaborative Research in Computational Neuroscience (CRCNS) program under award number IOS-1131948. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agencies.

CITATION: Douglas Ollerenshaw, et al., “The adaptive trade-off between detection and discrimination in cortical representations and behavior,” (NEURON, March 2014). (http://dx.doi.org/10.1016/j.neuron.2014.01.025).

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Writer: Brett Israel

The device integrates ultrasound transducers with processing electronics on a single 1.4 millimeter silicon chip. On-chip processing of signals allows data from more than a hundred elements on the device to be transmitted using just 13 tiny cables, permitting it to easily travel through circuitous blood vessels. The forward-looking images produced by the device would provide significantly more information than existing cross-sectional ultrasound.

Researchers have developed and tested a prototype able to provide image data at 60 frames per second, and plan next to conduct animal studies that could lead to commercialization of the device.

“Our device will allow doctors to see the whole volume that is in front of them within a blood vessel,” said F. Levent Degertekin, a professor in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology. “This will give cardiologists the equivalent of a flashlight so they can see blockages ahead of them in occluded arteries. It has the potential for reducing the amount of surgery that must be done to clear these vessels.”

Details of the research were published online in the February 2014 issue of the journal IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. Research leading to the device development was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health.

“If you’re a doctor, you want to see what is going on inside the arteries and inside the heart, but most of the devices being used for this today provide only cross-sectional images,” Degertekin explained. “If you have an artery that is totally blocked, for example, you need a system that tells you what’s in front of you. You need to see the front, back and sidewalls altogether. That kind of information is basically not available at this time.”

The single chip device combines capacitive micromachined ultrasonic transducer (CMUT) arrays with front-end CMOS electronics technology to provide three-dimensional intravascular ultrasound (IVUS) and intracardiac echography (ICE) images.  The dual-ring array includes 56 ultrasound transmit elements and 48 receive elements. When assembled, the donut-shaped array is just 1.5 millimeters in diameter, with a 430-micron center hole to accommodate a guide wire.

Power-saving circuitry in the array shuts down sensors when they are not needed, allowing the device to operate with just 20 milliwatts of power, reducing the amount of heat generated inside the body. The ultrasound transducers operate at a frequency of 20 megahertz (MHz).

Imaging devices operating within blood vessels can provide higher resolution images than devices used from outside the body because they can operate at higher frequencies. But operating inside blood vessels requires devices that are small and flexible enough to travel through the circulatory system. They must also be able to operate in blood.

Doing that requires a large number of elements to transmit and receive the ultrasound information. Transmitting data from these elements to external processing equipment could require many cable connections, potentially limiting the device’s ability to be threaded inside the body.

Degertekin and his collaborators addressed that challenge by miniaturizing the elements and carrying out some of the processing on the probe itself, allowing them to obtain what they believe are clinically-useful images with only 13 cables.

“You want the most compact and flexible catheter possible,” Degertekin explained. “We could not do that without integrating the electronics and the imaging array on the same chip.”

Based on their prototype, the researchers expect to conduct animal trials to demonstrate the device’s potential applications. They ultimately expect to license the technology to an established medical diagnostic firm to conduct the clinical trials necessary to obtain FDA approval.

For the future, Degertekin hopes to develop a version of the device that could guide interventions in the heart under magnetic resonance imaging (MRI). Other plans include further reducing the size of the device to place it on a 400-micron diameter guide wire.

In addition to Degertekin, the research team included Jennifer Hasler, a professor in the Georgia Tech School of Electrical and Computer Engineering; Mustafa Karaman, a professor at Istanbul Technical University; Coskun Tekes, a postdoctoral fellow in the Woodruff School of Mechanical Engineering; Gokce Gurun and Jaime Zahorian, recent graduates of Georgia Tech’s School of Electrical and Computer Engineering, and Georgia Tech Ph.D. students Toby Xu and Sarp Satir.

This research was supported by award number R01EB010070 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIBIB or NIH.

CITATION: Gokce Gurun, et al., “Single-Chip CMUT-on-CMOS Front-end System for Real-Time Volumetric IVUS and ICE Imaging,” (IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 2014). (http://dx.doi.org/10.1109/TUFFC.2014.6722610).

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There is no question that the Georgia Institute of Technology provides a mental workout. Academically, we rank with the best schools in the nation.

Georgia Tech also ranks among the most physically fit college campuses in the country. The Institute was listed #19 on the 50 Fittest Colleges in America by The Active Times. 

The hub of physical activity here helped Georgia Tech land so high on that ranking.

Read the full story:
Good as Gold: Inside Georgia Tech's Rec Center

AIMBE’s College of Fellows comprises a select group of about 1,500 members who have made significant and transformational contributions to medical and biological engineering. The College of Fellows is comprised of the top two percent of medical and biological engineers in the country.

McDevitt’s research program is focused on engineering stem cell technologies, which represents efforts to transform the potential of stem cells into clinically viable and useful regenerative therapies and diagnostic tools. To date, McDevitt has been responsible for over $10 million of research funding and has mentored more than 30 pre- and postdoctoral trainees and advised over 50 undergraduate researchers.  He has published over 50 articles in the top journals in his field and he has a number of local and national awards to his credit. McDevitt joined the BME department in 2004 and in 2010 was appointed as the director of Georgia Tech’s Stem Cell Engineering Center.

The nominations were peer reviewed by the College of Fellows Selection Committee, submitted for election, and approved by the votes of the entire College of Fellows to form AIMBE’s College of Fellows Class of 2014. McDevitt will be officially be inducted during AIMBE’s Annual Meeting at the National Academy of Sciences in Washington, D.C. on March 24, 2014.

A new technique for studying the structure of the RSV virion and the activity of RSV in living cells could help researchers unlock the secrets of the virus, including how it enters cells, how it replicates, how many genomes it inserts into its hosts – and perhaps why certain lung cells escape the infection relatively unscathed. That could provide scientists information they need to develop new antiviral drugs and perhaps even a vaccine to prevent severe RSV infections.

“We want to develop tools that would allow us to get at how the virus really works,” said Philip Santangelo, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We really need to be able to follow the infection in a single living cell without affecting how the virus infects its hosts, and this technology should allow us to do that.”

The research was supported by the National Institutes of Health’s National Institute of General Medical Sciences and published online ahead of print in the journal ACS Nano on December 30, 2013. While RSV will be the first target for the work, the researchers believe the imaging technique they developed could be used to study other RNA viruses, including influenza and Ebola.

“We’ve shown that we can tag the genome using our probes,” explained Santangelo. “What we’ve learned from this is that the genome does get incorporated into the virion, and that the virus particles created are infectious. We were able to characterize some aspects of the virus particle itself at super-resolution, down to 20 nanometers, using direct stochastic optical reconstruction microscopy (dSTORM) imaging.”

RSV can be difficult to study. For one thing, the infectious particle can take different forms, ranging from 10-micron filaments to ordinary spheres. The virus can insert more than one genome into the host cells and the RNA orientation and structure are disordered, which makes it difficult to characterize.

The research team, which included scientists from Vanderbilt University and Emory University, used a probe technology that quickly attaches to RNA within cells. The probe uses multiple fluorophores to indicate the presence of the viral RNA, allowing the researchers to see where it goes in host cells – and to watch as infectious particles leave the cells to spread the infection.

“Being able to see the genome and the progeny RNA that comes from the genome with the probes we use really give us much more insight into the replication cycle,” Santangelo said. “This gives us much more information about what the virus is really doing. If we can visualize the entry, assembly and replication of the virus, that would allow us to decide what to go after to fight the virus.”

The research depended on a new method for labelling RNA viruses using multiply-labeled tetravalent RNA imaging probes (MTRIPS). The probes consist of a chimeric combination of DNA and RNA oligonucleotide labeled internally with fluorophores tetravelently complexed to neutravidin. The chimeric combination was used to help the probes evade cellular defenses.

“There are lots of sensors in the cell that look for foreign RNA and foreign DNA, but to the cell, this probe doesn’t look like anything,” Santangelo explained. “The cell doesn’t see the nucleic acid as foreign.”

Introduced into cells, the probes quickly diffuse through a cell infected with RSV and bind to the virus’s RNA. Though binding tightly, the probe doesn’t affect the normal activities of the virus and allows researchers to follow the activity for days using standard microscopy techniques. The MTRIPS can be used to complement other probe technology, such as GFP and gold nanoparticles.

Work done by graduate student Eric Alonas to concentrate the virus was essential to the project, Santangelo said. The concentration had to be done without adversely affecting the infectivity of the virus, which would have impacted its ability to enter host cells.

“It took quite a bit of work to get the right techniques to concentrate the RSV,” he said. “Now we can make lots of infectious virus that’s labelled and can be stored so we can use it when we want to.”

To study the infection’s progress in individual cells, the researchers faced another challenge: living cells move around, and following them complicates the research. To address that movement, the laboratory of Thomas Barker – also in the Coulter Department – used micro-patterned fibronectin on glass to create 50-micron “islands” that contained the cells during the study.

Among the mysteries that the researchers would like to tackle is why certain lung cells are severely infected – while others appear to escape ill effects.

“If you look at a field of cells, you see huge differences from cell to cell, and that is something that’s not understood at all,” Santangelo said. “If we can figure out why some cells are exploding with virus while others are not, perhaps we can figure out a way to help the bad ones look more like the good ones.”

In addition to those already mentioned, the research team included James Crowe, professor of pediatrics at Vanderbilt University; Elizabeth Wright, assistant professor in the School of Medicine at Emory University; Daryll Vanover, Jeenah Jung, Chiara Zurla, Jonathan Kirschman, Vincent Fiore, and Alison Douglas from the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University; Aaron Lifland and Manasa Gudheti from Vutara Inc. in Salt Lake City, and Hong Yi from the Emory University School of Medicine.

One of the challenges of studying RSV is maintaining its activity in the laboratory setting – a problem parents of young children don’t share.

“When you handle this virus in the lab, you have to always be careful about it losing infectivity,” Santangelo noted. “But if you take a room full of children who have not been infected and let one infected child into the room, 15 minutes later all of the children will be infected.”

The research described here was supported by the National Institute of General Medical Sciences of the National Institutes of Health under contract R01 GM094198-01. Any conclusions or opinions expressed are those of the authors and do not necessarily represent the official views of the NIH.

CITATION: Eric Alonas, et al., “Combining Single RNA Sensitive Probes with Subdiffraction-Limited and Live-Cell Imaging Enables the Characterization of Virus Dynamics in Cells,” (ACS Nano, December 2013). (http://dx.doi.org/10.1021/nn405998v).

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Election as a fellow of AAAS, the world’s largest general scientific society, is an honor bestowed upon members by their peers. Fellows are recognized for meritorious efforts to advance science or its applications.

New fellows include:

• School of Interactive Computing Professor Henrik Christensen, cited “for contributions to applied estimation methods in mapping, robot localization, visual tracking and recognition, as well as national-level leadership of the robotics community.”
• School of Biology Professor Mark Hay, cited “for distinguished contributions in ecology, particularly for developing marine chemical ecology and for elucidating how chemical cues and signals structure populations, communities, and ecosystems.”
• School of Chemical and Biomolecular Engineering Professor Hang Lu, cited “for distinguished contributions to the field of engineering systems for high-throughput quantitative and systems biology, particularly for microfluidics, automation, image-based science, and phenomics.”
• School of Aerospace Engineering Professor Suresh Menon, cited “for distinguished and innovative contributions to the field of multi-scale computational simulation and modeling of turbulent combustion in power and propulsion systems.”

By feeding stem cells tiny particles made of magnetized iron oxide, scientists at Emory University and the Georgia Institute of Technology can then use magnets to attract the cells to a particular location in the body after intravenous injection.

The results are published online in the journal Small and will appear in an upcoming issue.

The paper was a result of collaboration between the laboratories of W. Robert Taylor of Emory, and Gang Bao of Georgia Tech. Taylor is professor of medicine and biomedical engineering and director of the Division of Cardiology at Emory University School of Medicine. Bao is professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. Co-first authors of the paper are postdoctoral fellows Natalia Landazuri and Sheng Tong. Landazuri is now at the Karolinska Institute in Sweden.

The type of cells used in the study, mesenchymal stem cells, are not embryonic stem cells. Mesenchymal stem cells can be readily obtained from adult tissues such as bone marrow or fat. They are capable of becoming bone, fat and cartilage cells, but not other types of cell such as muscle or brain. They secrete a variety of nourishing and anti-inflammatory factors, which could make them valuable tools for treating conditions such as cardiovascular disease or autoimmune disorders.

Magnetized iron oxide nanoparticles are already FDA-approved for diagnostic purposes with magnetic resonance imaging (MRI). Other scientists have tried to load stem cells with similar particles, but found that the coating on the particles was toxic or changed the cells’ properties. The nanoparticles used in this study have a polyethylene glycol coating that protects the cell from damage. Another unique feature is that the Emory/Georgia Tech team used a magnetic field to push the particles into the cells, rather than chemical agents used previously.

“We were able to load the cells with a lot of these nanoparticles and we showed clearly that the cells were not harmed,” Taylor said. “The coating is unique and thus there was no change in viability and perhaps even more importantly, we didn’t see any change in the characteristics of the stem cells, such as their capacity to differentiate. This was essentially a proof of principle experiment. Ultimately, we would target these to a particular limb, an abnormal blood vessel or even the heart.”

The particles are coated with the nontoxic polymer polyethylene glycol, and have an iron oxide core that is about 15 nanometers across. For comparison, a DNA molecule is two nanometers wide and a single influenza virus is at least 100 nanometers wide.

The particles appear to become stuck in cells’ lysosomes, which are parts of the cell that break down waste. The particles stay put for at least a week and leakage cannot be detected. The scientists measured the iron content in the cells once they were loaded up and determined that each cell absorbed roughly 1.5 million particles.

Once cells were loaded with iron oxide particles, the Emory/Georgia Tech team tested the ability of magnets to nudge the cells both in cell culture and in living animals. In mice, a bar-shaped rare earth magnet could attract injected stem cells to the tail. The magnet was applied to the part of the tail close to the body while the cells were being injected. Normally most of the mesenchymal stem cells would become deposited in the lungs or the liver.

To track where the cells went inside the mice, the scientists labeled the cells with a fluorescent dye. They calculated that the bar magnet made the stem cells six times more abundant in the tail. In addition, the iron oxide particles themselves could potentially be used to follow cells’ progress through the body.

“Next, we plan to focus on therapeutic applications in animal models where we will use magnets to direct these cells to the precise site need to affect repair and regeneration of new blood vessels,” Taylor said.

The research was supported by the National Heart Lung and Blood Institute’s Program of Excellence in Nanotechnology (HHSN268201000043C).

Reference: N. Landazuri, S. Tong, J. Suo, G. Joseph, D. Weiss, D.J. Sutcliffe, D.P. Giddens, G. Bao and W.R. Taylor. Magnetic targeting of human mesenchymal stem cells with internalized superparamagnetic iron oxide nanoparticles. Small, early view (2013)

Media Relations Contacts: Emory University – Quinn Eastman (404-727-7829) (qeastma@emory.edu); Georgia Tech – John Toon (404-894-6986) (jtoon@gatech.edu).
Writer: Quinn Eastman

Researchers are now reporting advances in these areas by using gelatin-based microparticles to deliver growth factors to specific areas of embryoid bodies, aggregates of differentiating stem cells. The localized delivery technique provides spatial control of cell differentiation within the cultures, potentially enabling the creation of complex three-dimensional tissues. The local control also dramatically reduces the amount of growth factor required, an important cost consideration for manufacturing stem cells for therapeutic applications.

The microparticle technique, which was demonstrated in pluripotent mouse embryonic cells, also offers better control over the kinetics of cell differentiation by delivering molecules that can either promote or inhibit the process. Based on research sponsored by the National Institutes of Health and the National Science Foundation, the developments were reported online July 1 in the journal Biomaterials and were presented at the 11th Annual International Society for Stem Cell Research meeting held in Boston June 12-15, 2013 .

“By trapping these growth factors within microparticle materials first, we are concentrating the signal they provide to the stem cells,” said Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We can then put the microparticle materials physically inside the multicellular aggregate system that we use for differentiation of the stem cells. We have good evidence that this technique can work, and that we can use it to provide advantages in several different areas.”

The differentiation of stem cells is largely controlled by external cues, including morphogenic growth factors, in the three-dimensional environment that surrounds the cells. Most stem cell researchers currently deliver the growth factors into liquid solutions surrounding the stem cell cultures with a goal of creating homogenous cultures of cells. Delivering the growth factors from microparticles, however, provides better control of the spatial and temporal presentation of the molecules that govern the growth and differentiation of the stem cells, potentially allowing formation of heterogeneous structures formed from different cells.

Groups of stem cells stick together as they develop, forming multicellular aggregates that form spheroids as they grow. The researchers took advantage of that by driving microparticles containing growth factor BMP4 or noggin – which inhibits BMP4 signaling – into layers of stem cells using centrifugation. When the cell aggregates formed, the microparticles became trapped inside.

The researchers used confocal imaging and flow cytometry to observe the differentiation process and found that growth factors in the microparticles directed the cells toward mesoderm and ectoderm tissues just as they do in solution-based techniques. But because the BMP4 and noggin molecules were directly in contact with the cells, much less growth factor was needed to spur the differentiation – approximately 12 times less than what would be required by conventional solution-based techniques.

“One of the major advantages, in a practical sense, is that we are using much less growth factor,” said McDevitt, who is also director of the Stem Cell Engineering Center at Georgia Tech. “From a bioprocessing standpoint, a lot of the cost involved in making stem cell products is related to the cost of the molecules that must be added to make the stem cells differentiate.”

Beyond more focused signaling, the microparticles also provided a localized control not available through any other technique. That allowed the researchers to create spatial differences in the aggregates – a possible first step toward forming more complex structures with different tissue types such as vasculature and stromal cells.

“To build tissues, we need to be able to take stem cells and use them to make many different cell types which are grouped together in particular spatial patterns,” explained Andres M. Bratt-Leal, the paper’s first author and a former graduate student in McDevitt’s lab. “This spatial patterning is what gives tissues the ability to perform higher order functions.”

After creating stem cell aggregates with microparticles containing different growth factors, the researchers observed a hemispherical organization of cells for several days, with the different cells remaining spatially segregated.

“We can see the microparticles had effects on one population that were different from the population that didn’t have the particles,” McDevitt said. “This may allow us to emulate aspects of how development occurs. We can ask questions about how tissues are naturally patterned. With this material incorporation, we have the ability to better control the environment in which these cells develop.”

The microparticles could also provide better control over the kinetics of cell differentiation. Including different amounts of molecules – one the growth factor and the other its antagonist – could vary the rate at which the stem cell differentiation proceeds.

While the research reported in this paper manipulated pluripotent mouse cells, the researchers have moved ahead in performing similar studies with human stem cells and achieved comparable types of results with the microparticle delivery approaches.

The developments not only help move stem cell technologies closer to the clinic, but also provide a new tool for research.

“Our findings will provide a significant new tool for tissue engineering, bioprocessing of stem cells and also for better studying early development processes such as axis formation in embryos,” said Bratt-Leal. “During development, particular tissues are formed by gradients of signaling molecules. We can now better mimic these signal gradients using our system.”

In addition to those already mentioned, the research team also included Anh H. Nguyen, Katy A. Hammersmith and Ankur Singh, all associated with Georgia Tech and Emory University when the research was conducted.

This research was supported by the National Institutes of Health (NIH) through award GM088291 and the National Science Foundation (NSF) through award CBET 0651739. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the NIH or NSF.

CITATION: Andres M. Bratt-Leal, Anh H. Nguyen, Katy A. Hammersmith, Ankur Singh and Todd C. McDevitt, “A Microparticle Approach to Morphogen Delivery within Pluripotent Stem Cell Aggregates,” Biomaterials, 2013). http://dx.doi.org/10.1016/j.biomaterials.2013.05.079

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Most swimming creatures rely on an undulating pattern of body movement to propel themselves through fluids. Though differences in body flexibility may lead to different swimming styles, scientists have found “neuromechanical phase lags” in nearly all swimmers. These lags are characterized by a wave of muscle activation that travels faster down the body than the wave of body curvature.

A study of the sandfish lizard – which “swims” through sand – led to development of the new model, which researchers believe could also be used to study other swimming animals. Beyond assisting the study of locomotion in a wide range of animals, the findings could also help researchers design efficient swimming robots.

“A graduate student in our group, Yang Ding, who is now at the University of Southern California, was able to develop a theory that could explain the kinematics of how this animal swims as well as the timing of the nervous system control signals,” said Daniel Goldman, an associate professor in the School of Physics at the Georgia Institute of Technology. “For animals swimming in fluids using an undulating movement, there are basic physical constraints on how they must activate their muscles. We think we have uncovered an important mechanism that governs this kind of swimming.”

The research was reported June 3 in the early edition of the journal Proceedings of the National Academy of Sciences. It was sponsored by the National Science Foundation’s Physics of Living Systems program, the Micro Autonomous Systems and Technology (MAST) program of the Army Research Office, and the Burroughs Wellcome Fund.

Undulatory locomotion is a gait in which thrust is produced in the opposite direction from a traveling wave of body bending. Because it is so commonly used by animals, this mode of locomotion has been widely used for studying the neuromechanical principles of movement.

Sarah Sharpe, the paper’s second author and a graduate student in Georgia Tech’s Interdisciplinary Bioengineering Program, led laboratory experiments studying undulatory swimming in sandfish lizards. She used X-ray imaging to visualize how the animals swam through sand that was composed of tiny glass spheres.

At the same time their swimming movements were being tracked, a set of four hair-thin electrodes implanted in the lizards’ bodies were providing information on when their muscles were activated. The two information sources allowed the researchers to compare the electrical muscle activity to the lizards’ body motion.

“The lizards propagate a wave of muscle activations, contracting the muscles close to their heads first, then the muscles at the midpoint of their body, then their tail,” said Sharpe. “They send a wave of muscle of contraction down their bodies, which creates a wave of curvature that allows them to swim. This wave of activation travels faster than the wave of curvature down the body, resulting in different timing relationships, known as phase differences, between muscle contracts and bending along the body.”

Sand acts like a frictional fluid as the sandfish swims through it. However, a sandfish swimming through sand is simpler to model than a fish swimming through water because the sand lacks the vortices and other complex behavior of water – and the friction of the sand eliminates inertia.

“Theoretically, it is difficult to calculate all of the forces acting on a fish or an eel swimming in a real fluid,” said Goldman. “But for a sandfish, you can calculate pretty much everything.”
The relative simplicity of the system allowed the research team – which also included Georgia Tech professor Kurt Wiesenfeld – to develop a simple model showing how the muscle activation relates to motion. The model showed that combining synchronized torques from distant points in the lizards’ bodies with local traveling torques is what creates the neuromechanical phase lag.

“This is one of the simplest, if not the simplest, models of swimming that reproduces the neuromechanical phase lag phenomenon,” Sharpe said. “All we really had to pay attention to was the external forces acting on an animal’s body. We realized that this timing relationship would emerge for any undulatory animal with distributed forces along its body. Understanding this concept can be used as the foundation to begin understanding timing patterns in all other swimmers.”

The sandfish swims using a simple single-period sinusoidal wave with constant amplitude. A key finding that facilitated the model’s development was that the sandfish’s body is extremely flexible, allowing internal forces – body stiffness – to be ignored.

“This animal turns out to be like a little limp noodle,” said Goldman. “Having that result in the theory makes everything else pop out.”

The model shows that the waveform used by the sandfish should allow it to swim the farthest with the least expenditure of energy. Swimming robots adopting the same waveform should therefore be able to maximize their range.

Goldman and his colleagues have been studying the sandfish, a native of the northern African desert, for more than six years.

“Sandfish are among the champions of all sand diggers, swimmers and burrowers,” said Goldman. “This lizard has provided us with an interesting entry point into swimming because its environment is surprisingly simple and behavior is simple. It turns out that this little sand-dweller may be able to tell us things about swimming more generally.”

This research has been supported by the National Science Foundation Physics of Living Systems (PoLS) under grants PHY-0749991 and PHY-1150760, by the U.S. Army Research Laboratory’s (ARL) Micro Autonomous Systems and Technology (MAST) Program under cooperative agreement W911NF-11-1-0514, and by the Burroughs Wellcome Fund Career Award. Any conclusions are those of the authors and do not necessarily represent the official views of the NSF or ARL.

CITATION: Yang Ding, Sarah Sharpe, Kurt Wiesenfeld and Daniel Goldman, “Emergence of the advancing neuromechanical phase in resistive force dominated medium,” (Proceedings of the National Academy of Sciences, 2013).

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The group spent the morning highlighting NIH funded research. Scientists representing Georgia Tech included Robert Guldberg, Ph.D., executive director of the Petit Institute for Bioengineering and Bioscience and professor in mechanical engineering, who spoke to Collins about the Regenerative Engineering and Medicine Center, a partnership between Emory University and Georgia Tech focused on endogenous repair and healing of nerves, bone, metabolic and cardiac applications. 

Todd McDevitt, Ph.D., director of the Stem Cell Engineering Center and associate professor in biomedical engineering at Georgia Tech, presented four projects funded with NIH dollars, including wound healing studies from a “Transformative Research Award,” a program developed to fund “high-risk, high-reward” science under the NIH’s Common Fund.

“Given that Dr. Collins recently dedicated a blog post on the ongoing research of Andrés García, Todd McDevitt, Hang Lu and Steve Stice from UGA, we were excited to share the great work being done in regenerative medicine and in stem cells,” explained Stephen Cross, Ph.D., executive vice president for research. “Bob and Todd were able to present ongoing NIH funded work for which Dr. Collins expressed both admiration and strong support.” 

Later that morning, administration from each university traveled to the Centers for Disease Control and Prevention, where they were joined by representatives from Clark Atlanta University, Georgia Regents University, Georgia Southern University and Mercer University for further discussions with Congressman Jack Kingston, Collins and Tom Frieden, M.D., M.P.H, director for the Center for Disease Control.  Each representative highlighted their NIH and/or CDC funded research as well as shared concerns regarding sequestration impacts on each university’s budget and ultimately the state’s economy.  Representatives also provided Collins and Frieden with suggestions on specific grant programs and reporting, peer review processes and programs aimed at diversifying the healthcare workforce.    

Due to the sequestration, the NIH’s budget will fall by $1.71 billion in 2013, which represents a 5% decrease.  As a result, NIH expects to fund 703 fewer new and competing research grants this year.

This decline in funding will have an impact on our Georgia universities, including Georgia Tech, which was awarded $41.3 million from the NIH in 2012.  NIH estimates that every $1 in NIH funding generates $2.21 in local economic growth.

As for how these cuts will affect individual research labs, that may not be known for some time. However, Collins is already seeking anecdotes of the sequestration’s impact via a twitter discussion using the hashtag #NIHSequesterImpact. 

Georgia Tech has created a sequestration information webpage, which includes the latest updates from Georgia Tech and many of its federal search sponsors. http://tlw-proxy.gatech.edu/research/faculty-and-staff-resources/sequestration-updates

The Institute’s College of Engineering is ranked No. 5 and all 11 Engineering programs ranked within the top 10, including industrial engineering (No. 1), biomedical and bioengineering (No. 2), civil (No. 4), aerospace (No. 5), electrical (No. 5), environmental (No. 5) computer (No. 5), mechanical (No. 5), materials (No. 9), chemical (No. 10) and nuclear (No. 10).

“Georgia Tech’s continued recognition within the U.S. News & World Report graduate rankings is a reflection of the consistent quality and ongoing success of our graduate programs,” said Georgia Tech President G. P. “Bud” Peterson.

The Scheller College of Business MBA program ranked No. 27, while the part-time evening MBA program also ranked highly at No. 24.

Researchers exploring the complex stream of cellular signals produced by the body in response to a traumatic injury believe the initial response – formation of a blood clot – may control subsequent healing. Using that information, they’re developing new biomaterials, including artificial blood platelets laced with regulatory chemicals that could be included in an injector device the size of an iPhone. Soldiers wounded in action could use the device to treat themselves, helping control bleeding, stabilizing the injury and setting the right course for healing.

Formation of “designer” blood clots from the artificial platelets would be triggered by the same factor that initiates the body’s natural clotting processes. In animal models, the synthetic platelets reduced clotting time by approximately 30 percent, though the materials have not yet been tested in humans.

“The idea is to have on the battlefield technologies that would deliver a biomaterial capable of finding where the bleeding is happening and augmenting the body’s own clotting processes,” said Thomas Barker, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Simultaneously, the material would help instruct the biochemistry and biophysics of the clot structure that would govern subsequent healing.”

Barker presented information on the research Friday, Feb. 15 at the annual meeting of the American Association for the Advancement of Science (AAAS). The research has been sponsored in part by the National Institutes of Health (NIH), by the U.S. Department of Defense through the Center for Advanced Bioengineering for Soldier Survivability at Georgia Tech, and by an American Heart Association postdoctoral fellowship to Ashley Brown, a postdoctoral fellow working on the project.

After an injury, the most critical need is to stop the bleeding. But as traumatic injuries heal, they often produce significant scarring that is difficult to treat. Georgia Tech researchers are working on both sides of the problem, developing cell signaling techniques that may head off the formation of scars – as well as techniques for addressing the fibrosis that is often the long-term result. Beyond helping halt the bleeding, the synthetic platelets would deliver regulatory chemicals designed to prevent scarring.

“The blood clot actually ends up directing how the entire wound healing process is going to occur,” Barker said. “The initial clot matrix instructs very specific cellular behaviors which have consequences for the next wave of cells that comes in to do specific jobs, which have consequences for the next wave of cells. If we can modify that initial clot, it can become the three-dimensional matrix needed to build the regenerated or repaired tissue.”

The synthetic platelets, made from tiny structures known as hydrogels, could be injected into the bloodstream where they would circulate until activated by the body’s own clotting processes. Once activated, the particles – which are about one micron in diameter – would change shape, converting to a thin film that would help seal wounds. To develop these hydrogels, Barker is collaborating with Andrew Lyon, a professor in Georgia Tech’s School of Chemistry and Biochemistry.

The bloodstream contains proteins known as fibrinogen that are the precursors for fibrin, the polymer that provides the basic structure for natural blood clots. When they receive the right signals from a protein called thrombin, these precursors polymerize at the site of the bleeding. To prevent unintended activation of their synthetic platelets, the researchers use the same trigger.

The researchers followed a process known as molecular evolution to develop an antibody that could be attached to the hydrogels to cause their form to change when they encounter thrombin-activated fibrin. The resulting antibody has high affinity for the polymerized form of fibrin and low affinity for the precursor.

“We knew the molecule that we wanted and we knew the domains that were critical for recognition,” Barker said. “The primary design concept was the ability to recognize an active, forming clot from the soluble, inactive precursor.”

The artificial platelets have so far been tested in rats, and separately using in vitro simulated endothelial systems in the laboratory of Wilbur Lam, an assistant professor at Emory University in Atlanta. Though the work is a long way from a device that could be used on the battlefield, Barker envisions transitioning the research to a startup company that develop the technology to improve survivability for wounded soldiers.

“You could have it literally in the pocket of any soldier, who could pop it out when needed,” Barker explained. “As the needle is extended, you would break the package of freeze-dried particles. The device would then be placed on the abdomen, where the particles would be injected into the bloodstream. They would circulate inactive until they encountered the initiation of clotting.”

Once the bleeding was stopped, cytokines and anti-inflammatory compounds within the “designer” clot could help determine the phenotype that should be adopted by healing cells and regulate their behavior. That would set the stage for the subsequent healing process.

To help soldiers already suffering from the effects of fibrosis – the contraction of scarred tissue – the researchers are developing a polymer to which a natural peptide is attached. The peptide helps regulate the repair process that produces scars and could ultimately help reduce or reverse the effects of fibrosis. The technique has reversed the effects of pulmonary fibrosis in an animal model.

Though the research focuses on the needs of soldiers injured on the battlefield, many of the technologies could ultimately find civilian use. Because the artificial platelets would only activate when the encounter thrombin-activated fibrin, they could be used by emergency medical technicians treating patients in which internal bleeding is suspected, Barker said.

This research is supported by the National Institutes of Health (NIH) under contract R21EB013743 and by the U.S. Department of Defense (DoD) under contract W81XWH110306. The conclusions are those of the authors and do not necessarily represent the official views of the NIH or the DoD.

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The study’s findings are outlined in the journal Molecular Cell and describe a surprising new aspect of cell adhesion involving the family of cell adhesion molecules known as integrins, which are found on the surfaces of most cells. The research uncovered a phenomenon termed “cyclic mechanical reinforcement,” in which the length of time during which bonds exist is extended with repeated pulling and release between the integrins and ligands that are part of the extracellular matrix to which the cells attach.

Professor Martin Humphries, dean of the faculty of life sciences at the University of Manchester and one of the paper’s co-authors, says the study suggests some new capabilities for cells: “This paper identifies a new kind of bond that is strengthened by cyclical applications of force, and which appears to be mediated by complex shape changes in integrin receptors. The findings also shed light on a possible mechanism used by cells to sense extracellular topography and to aggregate information through ‘remembering’ multiple interaction events.”

The cyclic mechanical reinforcement allows force to prolong the lifetimes of bonds, demonstrating a mechanical regulation of receptor-ligand interactions and identifying a molecular mechanism for strengthening cell adhesion through cyclical forces.

“Many cell functions such as differentiation, growth and the expression of particular genes depend on cell interaction with the ligands of the intracellular matrix,” said Cheng Zhu, a professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and the study’s corresponding author.  “The cells respond to their environment, which includes many mechanical aspects. This study has extended our understanding of how connections are made and how mechanical forces regulate interactions.”

The research was published online by the journal on February 14th. The work was supported by the National Institutes of Health (NIH) and the Wellcome Trust.

Cells of the body regulate adhesion in response to both internally- and externally-applied forces. This is particularly important to adhesion mediated by proteins such as integrins that connect the extracellular matrix to the cytoskeleton – and provide cells with both mechanical anchorages and the means to initiate signaling.

Using delicate force measuring equipment, researchers in Zhu’s lab and the laboratory of Andres Garcia – a professor in the Woodruff School of Mechanical Engineering at Georgia Tech – collaborated to study adhesion between integrin and fibronectin, a protein component of the extracellular matrix. What they found was that cyclic forces applied to the bond switch it from a short lived state – with lifetimes of about one second – to a long-lived state that can exist for more than a hundred seconds.

“Force can be very important in biology,” said Zhu. “Force has direction, magnitude and duration, so in describing its effects on biological systems, you have to use a more complete language.”

Zhu, Garcia and Georgia Tech graduate students Fang Kong, William Parks and David Dumbauld – along with postdoctoral fellow Zenhai Li – used two different mechanical techniques to study the strength of bonds between integrin and fibronectin. One technique measured the bond strengths in purified molecules, while the other studied the effects of them in their native cellular environment.

“We have very precise force transducers that allow us to measure force on the scale of pico-newtons,” said Zhu. “We prepare the samples in such a way that we engage only one bond, then we control the application of force and observe what happens.”

The researchers first used an atomic force microscope to bring the integrin molecule together with the fibronectin, then separate the two. Instruments measured the pico-newton forces required to separate the molecules, and found that the duration of the bonds increased with the repetition of the contacts.

The second technique, known as BFP, involved the use of a fibronectin-bearing glass bead attached to a red blood cell aspirated by a micropipette. Integrin expressed on the micropipette-aspirated cell was pressed into the bead, then pulled away over repeated cycles.Lifetime measurement confirmed that repeated pulling increased the longevity of the bonds.

The researchers studied two integrins, part of a family of 24 related molecules that operate in humans. In future work, they hope to determine whether or not the cyclic mechanical reinforcement they observed is a universal property of many cellular adhesion molecules.

The researchers also hope to explore how cells use this cyclic mechanical reinforcement. Because many disease processes result from abnormal cellular adhesion mechanisms, a better understanding could provide insights into how cardiovascular disease, cancer and immune system disorders operate.

“The findings of the paper have deep implications for our understanding of force-regulated signaling,” added Humphries. “There is abundant biological evidence for profound effects of extracellular tensility and elasticity in controlling processes such as cancer cell proliferation and stem cell differentiation, but the mechanisms whereby this information is transduced across the outer cell membrane are unclear.”

This research was supported by the National Institutes of Health (NIH) under grants AI44902 and GM065918. The conclusions are those of the authors and do not necessarily represent the official views of the NIH.

CITATION: Kong, F., et al., Cyclic Mechanical Reinforcement of Integrin-Ligand Interactions, Molecular Cell (2013). http://dx.doi.org/10.1016/j.molcel.2013.01.015

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“The Institute has gone to great lengths to improve our bike facilities on campus, installing hundreds of new bike racks, safer intersection treatments, and miles of new lanes and sharrows,” said Aaron Fowler, campus transportation planner in Parking & Transportation Services. “But with this allocation of $2.5 million in bike improvements by the City of Atlanta, we get to take a major step in improving our bike connections into campus.” 

In Midtown, bike lanes will be added to the 10th Street bridge refurbishment, between Fowler and Williams Streets, and from Piedmont Avenue to Monroe Drive, connecting to the BeltLine Eastside Trail. Lanes will also be added to Hemphill Avenue in Home Park between 10th and 14th Streets. Improvements will be made to bike lanes already present on West Peachtree, running from 10th Street to North Avenue, and Fifth Street, from Williams Street to Piedmont Avenue. 

Further southwest, the city’s first bike boulevard will be created near Atlanta University Center on James P. Brawley Drive, from Jefferson Street to Greensferry Avenue. Downtown, improvements will be made to the Peachtree Street corridor, from Pine Street to Peachtree Center Avenue. Other projects will improve connectivity in Inman Park, Castleberry Hill, Grant Park and other eastside areas. Some projects will use cycle tracks instead of bike lanes, providing more separation from motor vehicle traffic than just a painted lane.

According to a 2012 commuter survey conducted by Parking & Transportation Services, 8 percent of the campus community commutes by bike; however, another 24 percent voiced an interest in biking if there were safer, more convenient bike paths available. Some of the slated city projects coincide with items in a proposed Campus Bike Master Plan and work with existing lanes and sharrows on campus.

“These projects will only further our mission in promoting sustainability on campus and will give people the commute alternatives they desire,” said Fowler, who believes this is only the beginning of improved bicycle connectivity for Atlanta in the next few years.

The five City of Atlanta projects closest to campus include:

1. Fifth Street Bike Lanes ($65,715): This project will upgrade the existing bicycle lanes along Fifth Street that connect the Georgia Tech campus to the Peachtree Street corridor and Midtown residential district, one of the busiest cycling corridors in the city. Scope includes pavement patching, long-lasting thermoplastic pavement marking installation, addition of green pavement markings at key conflict points, installation of enhanced parking/regulatory signage and bicycle wayfinding signs and the construction of new bicycle treatments at intersections with other designated bicycle connections.
2. Hemphill Avenue Bike Lanes ($55,019): This project will install bicycle lanes along the northern section of Hemphill Avenue from 10th to 14th Streets. An on-street parking modification study will be conducted to determine the feasibility of reducing the roadway to two travel lanes and a single on-street parking lane. Scope includes pavement patching, long-lasting thermoplastic pavement marking installation, addition of green pavement markings at key conflict points, installation of enhanced parking/regulatory signage and bicycle wayfinding signs and the construction of new bicycle treatments at intersections with other designated bicycle connections.
3. West Peachtree Street Bike Lanes ($62,500): This project will upgrade the existing bicycle lane along West Peachtree Street that connects the MARTA North Avenue Station to the Georgia Tech Campus and points north. Scope includes pavement patching, railroad crossing improvements, long-lasting thermoplastic pavement marking installation, addition of green pavement markings at key conflict points, installation of enhanced parking/regulatory signage and bicycle wayfinding signs and the construction of new bicycle treatments at intersections with other designated bicycle connections.
4. 10th Street Bridge Refurbishment with Bike Facilities ($125,000): This funding will serve as the City of Atlanta's contribution toward the bicycle component of the Midtown Alliance 10th Street Bridge Improvement Project. This project will improve bicycle and pedestrian facilities, add lights, landscaping and decorative fencing.
5. 10th Street Cycle Track @ Atlanta BeltLine Intersection ($122,159): This project will construct a two-way cycle track along the 10th Street corridor, from Charles Allen Drive to Piedmont Avenue to tie into the planned two-way cycle track between Charles Allen Drive and Monroe Drive, connecting the Atlanta BeltLine Eastside Trail to Piedmont Park and Midtown. Due to right-of-way constraints, the section between Myrtle Street and Piedmont Avenue will likely consist of bicycle lanes. The project will be designed to meet the standards of the National Association of City Transportation Officials.

Research has shown that alternative antimicrobials such as PlyC can effectively kill bacteria. However, fundamental questions remain about how bacteria respond to the holes that these therapeutics make in their cell wall and what size holes bacteria can withstand before breaking apart. Answering those questions could improve the effectiveness of current antibacterial drugs and initiate the development of new ones.

Researchers at the Georgia Institute of Technology and the University of Maryland recently conducted a study to try to answer those questions. The researchers created a biophysical model of the response of a Gram-positive bacterium to the formation of a hole in its cell wall. Then they used experimental measurements to validate the theory, which predicted that a hole in the bacteria cell wall larger than 15 to 24 nanometers in diameter would cause the cell to lyse, or burst. These small holes are approximately one-hundredth the diameter of a typical bacterial cell.  

“Our model correctly predicted that the membrane and cell contents of Gram-positive bacteria cells explode out of holes in cell walls that exceed a few dozen nanometers. This critical hole size, validated by experiments, is much larger than the holes Gram-positive bacteria use to transport molecules necessary for their survival, which have been estimated to be less than 7 nanometers in diameter,” said Joshua Weitz, an associate professor in the School of Biology at Georgia Tech. Weitz also holds an adjunct appointment in the School of Physics at Georgia Tech.

The study was published online on Jan. 9, 2013 in the Journal of the Royal Society Interface. The work was supported by the James S. McDonnell Foundation and the Burroughs Wellcome Fund.

Common Gram-positive bacteria that infect humans include Streptococcus, which causes strep throat; Staphylococcus, which causes impetigo; and Clostridium, which causes botulism and tetanus. Gram-negative bacteria include Escherichia, which causes urinary tract infections; Vibrio, which causes cholera; and Neisseria, which causes gonorrhea.

Gram-positive bacteria differ from Gram-negative bacteria in the structure of their cell walls. The cell wall constitutes the outer layer of Gram-positive bacteria, whereas the cell wall lies between the inner and outer membrane of Gram-negative bacteria and is therefore protected from direct exposure to the environment.

Georgia Tech biology graduate student Gabriel Mitchell, Georgia Tech physics professor Kurt Wiesenfeld and Weitz developed a biophysical theory of the response of a Gram-positive bacterium to the formation of a hole in its cell wall. The model detailed the effect of pressure, bending and stretching forces on the changing configuration of the cell membrane due to a hole. The force associated with bending and stretching pulls the membrane inward, while the pressure from the inside of the cell pushes the membrane outward through the hole.

“We found that bending forces act to keep the membrane together and push it back inside, but a sufficiently large hole enables the bending forces to be overpowered by the internal pressure forces and the membrane begins to escape out and the cell contents follow,” said Weitz.

The balance between the bending and pressure forces led to the model prediction that holes 15 to 24 nanometers in diameter or larger would cause a bacteria cell to burst. To test the theory, Daniel Nelson, an assistant professor at the University of Maryland, used transmission electron microscopy images to measure the size of holes created in lysed Streptococcus pyogenes bacteria cells following PlyC exposure.

Nelson found holes in the lysed bacteria cells that ranged in diameter from 22 to 180 nanometers, with a mean diameter of 68 nanometers. These experimental measurements agreed with the researchers’ theoretical prediction of critical hole sizes that cause bacterial cell death.

According to the researchers, their theoretical model is the first to consider the effects of cell wall thickness on lysis.

“Because lysis events occur most often at thinner points in the cell wall, cell wall thickness may play a role in suppressing lysis by serving as a buffer against the formation of large holes,” said Mitchell.

The combination of theory and experiments used in this study provided insights into the effect of defects on a cell’s viability and the mechanisms used by enzymes to disrupt homeostasis and cause bacteria cell death. To further understand the mechanisms behind enzyme-induced lysis, the researchers plan to measure membrane dynamics as a function of hole geometry in the future.

CITATION: Mitchell GJ, Wiesenfeld K, Nelson DC, Weitz JS, “Critical cell wall hole size for lysis in Gram-positive bacteria,” J R Soc Interface 20120892 (2013): http://dx.doi.org/10.1098/rsif.2012.0892.

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• All BioE students are eligible - MUST BE CURRENTLY ENROLLED
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Nominations should be submitted to Chris Ruffin in the BioE Office. Nominations will be reviewed by the BioE Faculty Advisory Committee and winners will be announced at the BioE Reception on March 8, 2013 (Recruitment Day).

This patient-specific information may be helpful in developing personalized approaches to treat these tissue-destructive diseases.

“We measured significant variability in the amount of cathepsins produced by blood samples we collected from healthy individuals, which may indicate that a one-size-fits-all approach of administering cathepsin inhibitors may not be the best strategy for all patients with these conditions,” said Manu Platt, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

The study was published online on Oct. 19, 2012 in the journal Integrative Biology. This work was supported by the National Institutes of Health, Georgia Cancer Coalition, Atlanta Clinical and Translational Science Institute, and the Emory/Georgia Tech Regenerative Engineering and Medicine Center.

Platt and graduate student Keon-Young Park collected blood samples from 14 healthy individuals, removed white blood cells called monocytes from the samples and stimulated those cells with certain molecules so that they would become macrophages or osteoclasts in the laboratory. By doing this, the researchers recreated what happens in the body—monocytes receive these cues from damaged tissue, leave the blood, and become macrophages or osteoclasts, which are known to contribute to tissue changes that occur in atherosclerosis, cancer and osteoporosis.

Then the researchers developed a model that used patient-varying kinase signals collected from the macrophages or osteoclasts to predict patient-specific activity of four cathepsins: K, L, S and V.  

“Kinases are enzymes that integrate stimuli from different soluble, cellular and physical cues to generate specific cellular responses,” explained Platt, who is also a Georgia Cancer Coalition Distinguished Cancer Scholar. “By using a systems biology approach to link cell differentiation cues and responses through integration of signals at the kinase level, we were able to mathematically predict relative amounts of cathepsin activity and distinguish which blood donors exhibited greater cathepsin activity compared to others.”

Predictability for all cathepsins ranged from 90 to 95 percent for both macrophages and osteoclasts, despite a range in the level of each cathepsin among the blood samples tested.

“We were pleased with the results because our model achieved very high predictability from a simple blood draw and overcame the challenge of incorporating the complex, unknown cues from individual patients’ unique genetic and biochemical backgrounds,” said Platt.

According to Platt, the next step will be to assess the model’s ability to predict cathepsin activity using blood samples from individuals with the diseases of interest: atherosclerosis, osteoporosis or cancer.

“Our ultimate goal is to create an assay that will inform a clinician whether an individual’s case of cancer or other tissue-destructive disease will be very aggressive from the moment that individual is diagnosed, which will enable the clinician to develop and begin the best personalized treatment plan immediately,” added Platt.

Weiwei A. Li, who received her bachelor’s degree from the Coulter Department in 2010, also contributed to this study.

Research reported in this publication was supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR000454 and the Office of the Director of the NIH under award number 1DP2OD007433. The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NIH.

CITATION: Park, Keon-Young et al., “Patient specific proteolytic activity of monocyte-derived macrophages and osteoclasts predicted with temporal kinase activation states during differentiation,” Integrative Biology (2012): http://dx.doi.org/10.1039/C2IB20197F.

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Based on electron beam-induced deposition (EBID), the work is believed to be the first to connect multiple shells of a multi-walled carbon nanotube to metal terminals on a semiconducting substrate, which is relevant to integrated circuit fabrication. Using this three-dimensional fabrication technique, researchers at the Georgia Institute of Technology developed graphitic nanojoints on both ends of the multi-walled carbon nanotubes, which yielded a 10-fold decrease in resistivity in its connection to metal junctions.

The technique could facilitate the integration of carbon nanotubes as interconnects in next-generation integrated circuits that use both silicon and carbon components. The research was supported by the Semiconductor Research Corporation, and in its early stages, by the National Science Foundation. The work was reported online October 4, 2012, by the journal IEEE Transactions on Nanotechnology.

“For the first time, we have established connections to multiple shells of carbon nanotubes with a technique that is amenable to integration with conventional integrated circuit microfabrication processes,” said Andrei Fedorov, a professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech. “Connecting to multiple shells allows us to dramatically reduce the resistance and move to the next level of device performance.”

In developing the new technique, the researchers relied on modeling to guide their process parameters. To make it scalable for manufacturing, they also worked toward technologies for isolating and aligning individual carbon nanotubes between the metal terminals on a silicon substrate, and for examining the properties of the resulting structures. The researchers believe the technique could also be used to connect multi-layered graphene to metal contacts, though their published research has so far focused on carbon nanotubes.

The low-temperature EBID process takes place in a scanning electron microscope (SEM) system modified for material deposition. The SEM’s vacuum chamber is altered to introduce precursors of the materials that researchers would like to deposit. The electron gun normally used for imaging of nanostructures is instead used to generate low energy secondary electrons when the high energy primary electrons impinge on the substrate at carefully chosen locations. When the secondary electrons interact with hydrocarbon precursor molecules introduced into the SEM chamber, carbon is deposited in desired locations.

Unique to the EBID process, the deposited carbon makes a strong, chemically-bonded connection to the ends of the carbon nanotubes, unlike the weakly-coupled physical interface made in traditional techniques based on metal evaporation. Prior to deposition, the ends of the nanotubes are opened using an etching process, so the deposited carbon grows into the open end of the nanotube to electronically connect multiple shells. Thermal annealing of the carbon after deposition converts it to a crystalline graphitic form that significantly improves electrical conductivity.

“Atom-by-atom, we can build the connection where the electron beam strikes right near the open end of the carbon nanotubes,” Fedorov explained. “The highest rate of deposition occurs where the concentration of precursor is high and there are a lot of secondary electrons. This provides a nanoscale sculpturing tool with three-dimensional control for connecting the open ends of carbon nanotubes on any desired substrate.”

Multi-walled carbon nanotubes offer the promise of higher information delivery throughput for certain interconnects used in electronic devices. Researchers have envisioned a future generation of hybrid devices based on traditional integrated circuits but using interconnects based on carbon nanotubes.  

Until now, however, resistance at the connections between the carbon structures and conventional silicon electronics has been too high to make the devices practical.

“The big challenge in this field is to make a connection not just to a single shell of a carbon nanotube,” said Fedorov. “If only the outer wall of a carbon nanotube is connected, you really don’t gain much because most of the transmission channel is under-utilized or not utilized at all.”

The technique developed by Fedorov and his collaborators produces record low resistivity at the connection between the carbon nanotube and the metal pad. The researchers have measured resistance as low as approximately 100 Ohms – a factor of ten lower than the best that had been measured with other connection techniques.

“This technique gives us many new opportunities to go forward with integrating these carbon nanostructures into conventional devices,” he said. “Because it is carbon, this interface has an advantage because its properties are similar to those of the carbon nanotubes to which they are providing a connection.”

The researchers don’t know exactly how many of the carbon nanotube shells are connected, but based on resistance measurements, they believe at least 10 of the approximately 30 conducting shells are contributing to electrical conduction.

However, handling carbon nanotubes poses a significant challenge to their use as interconnects. When formed through the electric arc technique, for example, carbon nanotubes are produced as a tangle of structures with varying lengths and properties, some with mechanical defects. Techniques have been developed to separate out single nanotubes, and to open their ends.

Fedorov and his collaborators – current and former graduate students Songkil Kim, Dhaval Kulkarni, Konrad Rykaczewski and Mathias Henry, along with Georgia Tech professor Vladimir Tsukruk – developed a method for aligning the multi-walled nanotubes across electronic contacts using focused electrical fields in combination with a substrate template created through electron beam lithography. The process has a significantly improved yield of properly aligned carbon nanotubes, with a potential for scalability over a large chip area.

Once the nanotubes are placed into their positions, the carbon is deposited using the EBID process, followed by graphitization. The phase transformation in the carbon interface is monitored using Raman spectroscopy to ensure that the material is transformed into its optimal nanocrystalline graphite state.

“Only by making advances in each of these areas can we achieve this technological advance, which is an enabling technology for nanoelectronics based on carbon materials,” he said. “This is really a critical step for making many different kinds of devices using carbon nanotubes or graphene.”

Before the new technique can be used on a large scale, researchers will have to improve their technique for aligning carbon nanotubes and develop EBID systems able to deposit connectors on multiple devices simultaneously. Advances in parallel electron beam systems may provide a way to mass-produce the connections, Fedorov said.

“A major amount of work remains to be done in this area, but we believe this is possible if industry becomes interested,” he noted. “There are applications where integrating carbon nanotubes into circuits could be very attractive.”

CITATION: Songkil Kim, et.al, Fabrication of an Ultra-Low-Resistance Ohmic Contact to MWCNT-Metal Interconnect Using Graphitic Carbon by Electron Beam Induced Deposition (EBID), IEEE Transactions on Nanotechnology (2012). http://dx.doi.org/10.1109/TNANO.2012.2220377

This research has been supported by the Semiconductor Research Corporation (SRC) under GRC grant 2008OJ1864.1281 and in part by the National Science Foundation (NSF) under grant DMI 0403671. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NSF or the SRC.

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Taking a short hop before a big jump could allow spring-based “pogo-stick” robots to reduce their power demands as much as ten-fold. The formula for the two-part jump was discovered by analyzing nearly 20,000 jumps made by a simple laboratory robot under a wide range of conditions.

“If we time things right, the robot can jump with a tenth of the power required to jump to the same height under other conditions,” said Daniel Goldman, an assistant professor in the School of Physics at the Georgia Institute of Technology. “In the stutter jumps, we can move the mass at a lower frequency to get off the ground. We achieve the same takeoff velocity as a conventional jump, but it is developed over a longer period of time with much less power.”

The research was reported October 26 in the journal Physical Review Letters. The work was supported by the Army Research Laboratory’s MAST program, the Army Research Office, the National Science Foundation, the Burroughs Wellcome Fund and the GEM Fellowship.

Jumping is an important means of locomotion for animals, and could be important to future generations of robots. Jumping has been extensively studied in biological organisms, which use stretched tendons to store energy.

The Georgia Tech research into robot jumping began with a goal of learning how hopping robots would interact with complicated surfaces – such as sand, granular materials or debris from a disaster. Goldman quickly realized he’d need to know more about the physics of jumping to separate the surface issues from the factors controlled by the dynamics of jumping.

Inspired by student-directed experiments on the dynamics of hopping in his nonlinear dynamics and chaos class, Goldman asked Jeffrey Aguilar, a graduate student in the George W. Woodruff School of Mechanical Engineering, to construct the simplest jumping robot.

Aguilar built a one-kilogram robot that is composed of a spring beneath a mass capable of moving up and down on a thrust rod. Aguilar used computer controls to vary the starting position of the mass on the rod, the amplitude of the motion, the pattern of movement and the frequency of movement applied by an actuator built into the robot’s mass. A high-speed camera and a contact sensor measured and recorded the height of each jump.

• Website shows how changes affect jumping

Aguilar and Goldman then collaborated with theorists Professor Kurt Wiesenfeld and Alex Lesov, from the Georgia Tech School of Physics, to explain the results of the experiments.

The researchers expected to find that the optimal jumping frequency would be related to the resonant frequency of the spring and mass system, but that turned out not to be true. Detailed evaluation of the jumps showed that frequencies above and below the resonance provided optimal jumping – and additional analysis revealed what the researchers called the “stutter jump.”

“The preparatory hop allows the robot to time things such that it can use a lower power to get to the same jump height,” Goldman explained. “You really don’t have to move the mass rapidly to get a good jump.”

The amount of energy that can be stored in batteries can limit the range and duration of robotic missions, so the stutter jump could be helpful for small robots that have limited power. Optimizing the efficiency of jumping could therefore allow the robots to complete longer and more complex missions.

But because it requires longer to perform than a simple jump, the two-step jump may not be suitable for all conditions.

“If you’re a small robot and you want to jump over an obstacle, you could use low power by using the stutter jump even though that would take longer,” said Goldman. “But if a hazard is threatening, you may need to generate the additional power to make a quick jump to get out of the way.”

For the future, Goldman and his research team plan to study how complicated surfaces affect jumping. They are currently studying the effects of sand, and will turn to other substrates to develop a better understanding of how exploration or rescue robots can hop through them.

Goldman’s past work has focused on the lessons learned from the locomotion of biological systems, so the team is also interested in what the robot can teach them about how animals jump. “What we have learned here can function as a hypothesis for biological systems, but it may not explain everything,” he said.

The simple jumping robot turned out to be a useful system to study, not only because of the interesting behaviors that turned up, but also because the results were counter to what the researchers had expected.

“In physics, we often study the steady-state solution,” Goldman noted. “If we wait enough time for the transient phenomena to die off, then we can study what’s left. It turns out that in this system, we really care about the transients.”

This research is supported by the Army Research Laboratory under cooperative agreement number W911NF-08-2-004, by the Army Research Office under cooperative agreement W911NF-11-1-0514, and by the National Science Foundation under contract PoLS PHY-1150760. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Army Research Laboratory, the Army Research Office or the National Science Foundation.

CITATION: Aguilar, Jeffrey et al., “Lift-off dynamics in a simple jumping robot,” Physical Review Letters (2012): http://prl.aps.org/abstract/PRL/v109/i17/e174301

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Georgia Tech’s efforts in addressing such needs have traditionally received recognition from various sources. Diverse Issues in Higher Education, for instance, ranks  the University No. 1 in multiple categories: engineering bachelor’s degrees awarded to all minority students, engineering doctoral degrees awarded to African Americans, engineering doctoral degrees awarded to Hispanics and engineering doctoral degrees awarded to all minority students. Hispanic Business Magazine also recently named Georgia Tech No. 1 among engineering graduate schools.

Dr. Rafael L. Bras, provost and executive vice president for Academic Affairs at Georgia Tech, accepted the award during NACME’s Awards Dinner and Celebration, and thanked all of the individuals and departments at Georgia Tech – from Enrollment Services to the College of Engineering – dedicated to attracting and supporting underrepresented students as they pursue careers in engineering.

“I am proud that our efforts to improve diversity span the full spectrum,” Bras said. “We work with all age groups to cultivate a diverse pipeline by increasing engineering awareness in the K-12 arena and exposing students to real-world, hands-on engineering experiences; we work with high school students; we celebrate our minority students and their accomplishments; and we have programs to promote graduate education – particularly in science, technology, engineering and math (STEM) fields – among women and underrepresented minorities.”

Bras added that Georgia Tech remains committed to its goals of diversity and inclusiveness and to providing the best education to all students.

“The support and recognition of great organizations like NACME is very much appreciated,” he said.

"I am truly honored by this award and recognition,” said García, who is a Woodruff Professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech. “The Society for Biomaterials has had a huge impact in my scientific and professional career and I am delighted to join past awardees from our community. I am also proud to represent my great colleagues along with past and present trainees from Georgia Tech who have contributed to this recognition."

The Society for Biomaterials is the oldest scientific organization in the field of biomaterials and has a mission of encouraging, fostering, promoting and advancing education, and research and development, in biomaterials science.  The society has grown to more than 2,000 members since its inception in 1974.

"García is an outstanding recipient of this award," said Buddy Ratner, Ph.D., professor of bioengineering and chemical engineering at the University of Washington, who recommended García for the Clemson award. "His strong commitment to polymeric biomaterials and to the modern biology of healing and regeneration, coupled with a fine intelligence, a charismatic personality and super-charged energy, has propelled his career and technical impact to the top of the discipline."

In addition to this award, the society announced that a pioneering publication by García was one of twenty-five articles selected as part of a special virtual edition of the Journal of Biomedical Materials Research celebrating the 100^th volume of the journal. The criteria for inclusion of a paper in the special issue was the identification of articles that, in their time, were considered novel, original, state-of-the-art, ground-breaking, and opened new areas of biomaterials research.

García’s work established the paradigm that cell response to material properties could be mediated by protein adsorption. This research established an experimental framework to analyze adhesive mechanisms controlling cell-surface interactions and provided a general strategy for surface-directed control of adsorbed protein activity to manipulate cell function in biomaterial and biotechnology applications.  This finding established a new strategy to direct cellular responses to biomaterials and has broad application to the engineering of materials to elicit specific biological responses.

The article, “Surface Chemistry Modulates Fibronectin Conformation and Directs Integrin Binding and Specificity to Control Cell Adhesion,” was co-authored by collaborator David M. Collard, a professor in the School of Chemistry and Biochemistry at Georgia Tech, and by Benjamin G. Keselowsky, who was then a graduate student in the García laboratory.  Keselowsky is now an associate professor at the University of Florida.

García’s research program focuses on engineering biomaterials that promote tissue repair and healing; quantitative analyses of mechanisms regulating cell adhesive forces; and cell-based therapies for regenerative medicine.  These integrated cellular engineering strategies have provided new insights into mechanisms regulating cell-material interactions and established new approaches for the rational design of biomaterials and cell-delivery vehicles for regenerative medicine applications, including bone repair, vascularization and inflammation.

His laboratory’s research has led to advances across many areas of regenerative medicine including applications related to the bone and cartilage, angiogenesis, neurogenesis, inflammation, and implant integration with tissues.

García has co-authored papers in leading biomaterials, tissue engineering, and cell biology journals as well as several patents and invention disclosures.  He has received several distinctions throughout his successful career, including the NSF CAREER Award, Arthritis Investigator Award, Georgia Tech’s CETL/BP Junior Faculty Teaching Excellence Award, Young Investigator Award from the Society for Biomaterials, Petit Institute Above and Beyond Award and Georgia Tech’s Outstanding Interdisciplinary Activities Award.

Currently García serves as chair of the Interdisciplinary Bioengineering Graduate Program at Georgia Tech. He is also the director of a NIH/NIGMS biotechnology training grant on cell and tissue engineering.  He serves on the editorial boards of leading biomaterial and regenerative medicine journals as well as NIH and NSF review panels.  García has been recognized as a top Latino educator by the Society of Hispanic Professional Engineers and has been elected a Fellow of Biomaterials Science and Engineering by the International Union of Societies of Biomaterials Science and Engineering.

García joined Georgia Tech as assistant professor in 1998.  He received a B.S. in mechanical engineering with honors from Cornell University in 1991. He received M.S.E. in 1992 and Ph.D. in 1996 in bioengineering from the University of Pennsylvania. 

“This grant provides a unique training opportunity for top engineering graduate students looking to understand how to control stem cells into clinically relevant numbers,” stated Todd McDevitt, PhD.

McDevitt, associate professor in the Wallace H. Coulter Department of Biomedical Engineering is co-directing the IGERT program with Robert M. Nerem, professor emeritus of the George W. Woodruff School of Mechanical Engineering at Georgia Tech.  McDevitt is also director of the Stem Cell Engineering Center which administers this award.

Recently highlighted by Nature magazine as one of the “out of the box” manufacturing educational programs in the country, the $3 million NSF-funded IGERT was awarded to Georgia Tech in 2010 to educate and train the first generation of Ph.D. students in the translation and commercialization of stem cell technologies for diagnostic and therapeutic applications.

The Stem Cell Biomanufacturing IGERT program supports new incoming Georgia Tech Ph.D. students for their first two years of graduate school. The program offers a core curriculum in stem cell engineering and bioprocessing coupled with elective tracks in advanced technologies, public policy, ethics or entrepreneurship.

“The current state of the field of stem cell research offers a unique opportunity for engineers to contribute significantly to the generation of robust, reproducible and scalable methods for phenotypic characterization, propagation, differentiation and bioprocessing of stem cells,” McDevitt added.

Trainees are afforded opportunities to meet with leading experts in the field who visit as part of the Stem Cell Engineering seminar series, attend the annual stem cell engineering workshop, participate in outreach activities and interact with representatives from leading companies during Georgia Tech’s annual Bio Industry Symposium.

Georgia Tech's Stem Cell Biomanufacturing IGERT award will support at least 30 graduate students over the 5 years of the award.

2012 Trainees

Olivia Burnsed - Wallace H. Coulter Department of Biomedical Engineering

Efrain Cermeno - Wallace H. Coulter Department of Biomedical Engineering

Albert Cheng - Wallace H. Coulter Department of Biomedical Engineering

Jose Garcia - George W. Woodruff School of Mechanical Engineering

Emily Jackson - School of Chemical and Biomolecular Engineering

2011 Trainees

Tom Bongiorno – George W. Woodruff School of Mechanical Engineering

Rob Dromms – School of Chemical and Biomolecular Engineering

Devon Headen – Wallace H. Coulter Department of Biomedical Engineering

Greg Holst – George W. Woodruff School of Mechanical Engineering

Torri Rinker – Wallace H. Coulter Department of Biomedical Engineering

Shalini Saxena – School of Material Science & Engineering

Josh Zimmerman – Wallace H. Coulter Department of Biomedical Engineering

2010 Trainees

Amy Cheng – George W. Woodruff School of Mechanical Engineering

Alison Douglas – Wallace H. Coulter Department of Biomedical Engineering

Jennifer Lei – George W. Woodruff School of Mechanical Engineering

Douglas White – Wallace H. Coulter Department of Biomedical Engineering

Jenna Wilson – Wallace H. Coulter Department of Biomedical Engineering

“This year’s GAANN fellows were selected from an outstanding pool of applicants, who are carrying out high-impact research addressing a broad range of pharmaceutical needs” said Mark Prausnitz, PhD, Regents' professor and Love Family professor in Chemical & Biomolecular Engineering and director of CD4, who serves as the principle investigator of the program. 

The new class of fellows represent a diverse group of students from biomedical engineering, chemistry, chemical and biomolecular engineering and materials science and engineering.  

“While most academic training programs address one particular aspect of pharmaceutical research, at Georgia Tech, we have an integrative approach that brings together scientists and engineers from many disciplines to improve the process of pharmaceutical development that includes drug design, manufacturing and delivery. Through the GAANN training grant, we are training future leaders of pharmaceutical research who understand the complex, interconnected process of bringing a drug from idea to product,” Prausnitz added

Since the program’s inception in 2003, over 130 fellowships have been awarded.  Solicitation for the 2013-2013 fellows will take place beginning in April 2013.

The 2012-2013 GAANN fellows:

Rayaj Ahmed – Chemistry & Biochemistry
Samantha Au – Chemical & Biomolecular Engineering
W. Chris Edens – Biomedical Engineering
Hiroyuki Ichikawa – Chemistry & Biochemistry
Russell Jampol – Chemical & Biomolecular Engineering
Yoo Chun Kim – Chemical & Biomolecular Engineering
Jonathan Park – Chemical & Biomolecular Engineering
Michelle Razumov – Chemistry & Biochemistry
Mark Spears – Chemistry & Biochemistry
Maeling Tapp – Material Science and Engineering
Aubrey Tiernan – Chemical & Biomolecular Engineering
Alex Weller – Material Science and Engineering
Jenna Wilson – Biomedical Engineering 

A team of surgeons and university researchers recently reported promising results from a novel surgical connection intended to streamline blood flow between the heart and lungs of such infants.

Typically, the final stage of the Fontan procedure is performed by connecting a cylindrical conduit to the pulmonary arteries, forming a ‘T’ shaped junction. In a pilot study, six patients at Children’s Healthcare of Atlanta received a commercially available Y-shaped conduit for their Fontan procedure instead of the cylindrical conduit to create a smoother transition of the blood flow to the pulmonary arteries. Postoperative imaging data from the patients indicated improved blood flow distribution and similar energy efficiency when compared with computer simulations of two alternative connections the patients could have received instead of a Y-graft.

“Based on improved energy characteristics predicted by computer modeling for the Y-shaped conduit, we felt it was time to try it in the clinical realm,” said Kirk Kanter, M.D., chief of cardiothoracic surgery at Children’s Healthcare of Atlanta and professor of surgery at Emory University School of Medicine, who performed the operations. “The pilot study revealed that surgical implementation of a Y-graft for Fontan procedures is feasible and promising because early outcome was good in these patients.”

The surgical procedure and the postoperative outcomes were detailed in two articles recently published online in the Journal of Thoracic and Cardiovascular Surgery (articles available here and here). The research was funded by the National Institutes of Health and the American Heart Association.

Also involved in the study were Ajit Yoganathan, Ph.D., Regents’ professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University; W. James Parks, M.D., associate professor of pediatrics and radiology at Emory University and Children’s Healthcare of Atlanta at Egleston; Mark A. Fogel, M.D., director of cardiac magnetic resonance at The Children’s Hospital of Philadelphia; Georgia Tech School of Interactive Computing Professor Jarek Rossignac, Ph.D., and Coulter Department graduate student Christopher Haggerty.

The TCPC typically creates a four-way intersection. Blood from the upper half of the body enters the intersection from the top and blood from the lower body enters from the bottom. The blood flows collide and mix in the intersection before they are split and redirected 90 degrees toward the left or right pulmonary arteries. The collision of blood from the two veins at the intersection causes inefficient blood flow.

Because the blood flows passively from the body to the lungs without being pumped by the heart, it is assumed that any energy inefficiencies inherent in the construction of the Fontan pathway may translate into diminished life expectancy and quality of life.

Substituting a Y-shaped conduit should avoid the collision of blood in the intersection and enable a smooth and streamlined transition of the blood to the pulmonary arteries, which carry deoxygenated blood from the heart to the lungs.

For the pilot study, Kanter surgically implanted a commercially available Y-graft, made of a synthetic polymer called polytetrafluoroethylene, in each patient to direct flow from the lower half of the body to the left and right pulmonary arteries. This was a variation of a conduit design, called the Optiflo, which was patented by Yoganathan and colleagues for its ability to efficiently direct an even distribution of blood flow to the left and right pulmonary arteries.

After surgery, the researchers acquired magnetic resonance or computed tomography images to evaluate the operative connections. The images allowed Yoganathan and Haggerty to evaluate the hemodynamic outcomes of the surgical procedures for five of the six patients and compare them to the simulated outcomes of two alternative connections the patients could have received instead of a Y-graft.

They used the images to model blood flow through the arteries under resting and exercise conditions. These simulations assessed the robustness of each connection geometry because small inefficiencies under resting conditions may be amplified with higher flows.

Results for the patients who received the Y-graft showed balanced distribution of flow to both pulmonary arteries with minimal flow disturbance. The resistance of the vessels to blood flow at the connections varied considerably among patients, but the Y-graft results demonstrated resistance levels similar to the alternative connections in four patients and marked improvement in a fifth patient.

“We found desirable flow distribution characteristics using the Y-graft, but the flow efficiency performance fell short of the outcomes we previously predicted,” said Yoganathan. “The results suggest that the Y-graft performs as well as the standard procedure with a T-graft even when the Y-graft design is theoretically sub-optimal.”

The study allowed the researchers to identify ways of refining the surgical technique that should help them improve the theoretical efficiency of the conduit design. Before conducting future clinical trials, the research team plans to address two features of the Y-graft design that limited hemodynamic efficiency in the current study. They plan to introduce curvature to the Y-graft branches and extend the distance between the Y-graft branches to reduce continued interaction and mixing between the two blood streams.

Research reported in this publication was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) under award numbers HL67622 and HL098252 and by a Pre-Doctoral Fellowship Award from the American Heart Association (AHA) (10PRE372002). The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NIH.

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To address this problem, a startup company based on technology developed at the Georgia Institute of Technology is creating an efficient, safe and repeatable delivery method that protects cells from death and migration from the treatment site. Using microbead technology developed in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, SpherIngenics is producing protective capsules for the delivery of cell-based therapies.

Supported by a broad range of Georgia Tech initiatives, the company recently received a two-year $730,000 Phase II Small Business Innovation Research (SBIR) grant from the U.S. Department of Defense to continue development of the technology.

“When damaged tissue is being repaired by a cell-based therapy, our microbead technology ensures that cells travel to and remain in the targeted area while maintaining continued viability,” said SpherIngenics CEO Franklin Bost, who is also a professor in the Coulter Department. “This technology has the potential to reduce the cost of treatment by eliminating the need for multiple therapeutic procedures.”

Bost and Coulter Department Professors Barbara Boyan and Zvi Schwartz founded the company in 2007. They worked with the Georgia Tech Research Corporation to license five patents from Boyan’s lab for technology originally developed in the Georgia Tech/Emory Center for the Engineering of Living Tissue (GTEC), which was funded by a grant from the National Science Foundation. Then they secured $450,000, which included a Phase I SBIR grant from the U.S. Department of Defense and grants from the Georgia Research Alliance and the Coulter Foundation.

During Phase I of the SBIR grant, the researchers confirmed that as many as 250 human adult stem cells could remain viable in culture if they were encapsulated in a 200-micron-diameter bead made of natural algae materials and that they could release factors that enhance tissue regeneration.

“For the Phase II SBIR grant, we’re going to examine whether delivering microbeads full of stem cells can enhance cartilage repair and regeneration of craniofacial defects in an animal model,” said Boyan, who is the company’s chief scientific officer. Boyan is also the associate dean for research and innovation in the Georgia Tech College of Engineering, the Price Gilbert, Jr. Chair in Tissue Engineering at Georgia Tech, and a Georgia Research Alliance Eminent Scholar.

The company will perform this research in its laboratory space located in the Advanced Technology Development Center (ATDC) biosciences incubator.

The company’s ultimate goal is to commercialize the microbead technology for use in hospitals and by cell therapy companies. To help reach this goal, a group of students wrote a business plan for SpherIngenics last year through the Georgia Tech Scheller College of Business Technological Innovation: Generating Economic Results (TI:GER) program.

The team -- which included Coulter Department doctoral student Christopher Lee, Georgia Tech MBA students Chris Palazzola and Eric Diersen, and Emory University law students Bryan Stewart and Natalie Dana -- won third place in the 2011 Georgia Tech Business Plan Competition. The competition, while largely an education experience, provided students an opportunity to develop their venture ideas and present them to a panel of highly experienced judges in the venture capital, technology transfer and legal fields.

“The TI:GER team’s business plan helped us learn about where the market for our technology is right now and where it is going in the future, which is extremely valuable knowledge as we work toward determining the most promising pathway to market,” said Bost.

Additional members of the company include Anthony Nicolini, the principal investigator on the Phase II SBIR grant, and Joseph Williams, clinical director of craniofacial plastic surgery at Children’s Healthcare of Atlanta at Scottish Rite and clinical assistant professor in the Department of Plastic and Reconstructive Surgery at Emory University.

Research reported in this publication was supported by the U.S. Army Medical Research and Materiel Command under award numbers W81XWH-07-1-0219 and W81XWH-11-C-0071. The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the U.S. Government.

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“From a professional standpoint I am looking forward to expanding my research training and skill-set, which will provide a solid foundation as I begin my independent career in academic research,” said Timmins.

Timmins’ travel to London will enable him to develop computational methods and techniques required to construct computational fluid dynamic models.  He will use microtomography and magnetic resonance imaging data to understand biomechanical stimuli in the development of atherosclerosis.

"Luke will be working with a unique, hemodynamically altered model of atherosclerosis that allows for a multi-scale approach in understanding this disease.  Luke's knowledge of computational fluid dynamics will be a significant benefit to Rob Krams' research group,” Giddens explained. "In addition, Luke's visit will strengthen the long-standing professional relationship between my research group and Imperial College London, and serve as a greater benefit in further developing the linkages between bioengineering research in the Petit Institute and Imperial."

The Nerem International Travel Award was endowed by Nerem’s colleagues and friends in appreciation of the impact that Nerem has had on many. As the Petit Institute’s founding director, Nerem passionately served the community for 14 years and successfully led the institute to national and international prominence in the fields of bioengineering and bioscience.

“Everyone who knows Nerem, knows he loves to travel. His travels have brought him to all corners of the world and it is through his travel that he has served as a great champion of Georgia Tech, the Petit Institute and biocommunity as a whole,” stated Robert Guldberg, executive director of the Petit Institute.  

Beginning in 2005, this award has allowed trainees an opportunity to travel to a wide variety of international research universities and institutes, including the Karolinska Institute, Stockholm, Sweden; RIKEN Brain Science Institute, Japan; the National University of Singapore; University of Twente,The Netherlands; Queensland University of Technology, Australia; and Consorzio Interuniversitario Lombardo per L’Elaborazione Automatica, Milan, Italy.

“I am so proud of this annual award as it affords the opportunity for a trainee to broaden their research experiences by establishing an international collaboration and travel to another university or institution,” Nerem stated. “Opening one's eyes to new techniques and research facilities will have a profound impact on Timmins’ research and training.”

“It is truly is an honor to receive an award that bears Dr. Nerem's name given his distinguished dedication to bioengineering research and commitment to mentorship,” said Timmins. “I also want to sincerely thank the friends of Dr. Nerem’s and the Petit Institute for providing such an outstanding opportunity to its graduate students and post-docs.”

Timmins has co-authored nine well-cited peer reviewed publications, serving as lead author on five. He is co-author on 20 conference abstract proceedings and has given numerous presentations at engineering and clinical professional conferences. Timmins currently serves as an ad-hoc reviewer for over 12 journals and is a member of the Fluid Mechanics and Solid Mechanics Technical Committees of the ASME Bioengineering Division. In addition, Timmins also received an inaugural Whitaker International Fellowship from the Whitaker Program and was awarded an American Heart Association Postdoctoral Fellowship.

Fellows are appointed based on significant contributions to the biomaterials field as well as national and international recognition of accomplishments documented by a continuous productivity in biomaterials research and are considered role models in the biomaterials science and engineering field.

The Fellows program began in1992 after the constituent biomaterials societies of the World Biomaterials Congress recognized the need for public recognition of their members who have gained a status of excellent professional standing and earned high achievements in the biomaterials field. For this reason, the honorary status of "Fellow, Biomaterials Science and Engineering" (FBSE) was established.

Boyan and García have had significant accomplishments throughout their careers which include receiving awards from the Society for Biomaterials, authoring papers in leading biomaterials journals and they both have several biomaterials-related patents and invention disclosures.

Boyan’s research laboratory focuses on bone and cartilage cell biology and tissue engineering of musculoskeletal tissues. Researchers are investigating signaling pathways involved in implant osseointegration, or the connection between the bone and a material. Specifically, they are exploring how surface properties influence biological processes and pathways such as cell proliferation, differentiation, angiogenesis and apoptosis to better understand healing and regeneration.

Boyan was recently elected to the National Academy of Engineering and other 2012 awards include and the Orthopaedic Research Society Women's Leadership Forum Award and she was named a fellow of the International Team for Implantology.

García’s research activities center on analyses of cell adhesive forces and mechanotransduction, cell-biomaterial interactions and the engineering of biomaterials to control cell delivery and engraftment and tissue repair, including bone repair, therapeutic vascularization, pancreatic islet delivery for the treatment of diabetes, and inflammation and infection. These findings provide fundamental insights into mechanisms regulating cell-material interactions and constitute novel approaches to the engineering of bioactive materials for enhanced tissue repair.

García was awarded the Clemson Award for Basic Research from the Society of Biomaterials and will be presented with that award in New Orleans in October 2012. García serves on the editorial board of leading biomaterial and regenerative medicine journals as well as National Institutes of Health and National Science Foundation review panels.

Even though a single raindrop can weigh 50 times more than a mosquito, the insect is still able to fly through a downpour.

Georgia Tech researchers used high-speed videography to determine how this is possible. They found the mosquito’s strong exoskeleton and low mass render it impervious to falling raindrops.

The research team, led by Assistant Professor of Mechanical Engineering and Biology David Hu and his doctoral student Andrew Dickerson, found that mosquitoes receive low impact forces from raindrops because the mass of mosquitoes causes raindrops to lose little momentum upon impact. The results of the research will appear in the June 4 issue of the Proceedings of the National Academy of Sciences of the United States of America.

“The most surprising part of this project was seeing the robustness this small flyer has in the rain,” Dickerson said. “If you were to scale up the impact to human size, we would not survive. It would be like standing in the road and getting hit by a car.”

What the researchers learned about mosquito flight could be used to enhance the design and features of micro-airborne vehicles, which are increasingly being used by law enforcement and the military in surveillance and search-and-rescue operations.

To study how mosquitoes fly in the rain, the research team constructed a flight arena consisting of a small acrylic cage covered with mesh to contain the mosquitoes but permit entry of water drops. They used a water jet to simulate rain stream velocity and observed six mosquitoes flying into the stream. All the mosquitoes survived the collision.

“The collision force must equal the resistance applied by the insect,” Hu said. “Mosquitoes don’t resist at all, but simply go with the flow.”

The team also filmed free-flying mosquitoes that were subjected to rain drops. They found that upon impact the mosquito is adhered to the front of the drop for up to 20 body lengths.  

“To survive, the mosquito must eventually separate from the front of the drop,” Hu said. “The mosquito accomplishes this by using its long legs and wings, whose drag forces act to rotate the mosquito off the point of contact. This is necessary, otherwise the mosquito will be thrown into the ground at the speed of a falling raindrop.”

CD4 fellowship awards are expected to be announced by early July 2012 for funding starting Fall semester 2012 and continuing through Summer semester 2013 (i.e., for 12 months). The stipend for this fellowship will be at the standard stipend level of the department in which the fellow is enrolled plus a $3,000 supplement. This stipend will be paid with a combination of funds from the CD4 fellowship program and the fellow’s thesis advisor. The amount provided by the CD4 fellowship program will be determined by the fellow’s financial need level according to federal guidelines administered by the Georgia Tech financial aid office. In the past, financial need levels have varied widely, with a representative value of about $18,000. Thus, the cost-sharing contribution of the thesis advisor cannot be predicted until the fellow’s financial need level is determined. In addition, the CD4 fellowship program will provide $5,000 to support research, travel and educational activities by the fellow, in consultation with his/her advisor.

There are four eligibility requirements for a CD4 fellowship: (1) candidates must be U.S. citizens or permanent residents, (2) candidates must be pursuing a Ph.D. degree (although they need not have passed the qualifying exam yet), (3) candidates must have significant financial need and (4) research must be on at least one of the program focus areas: (i) drug design, (ii) development of drugs or genes and (iii) delivery of drugs or genes.

Drug design includes creation of new compounds for pharmaceutical applications. Drug development includes synthesis, purification and other aspects of drug production. Drug delivery includes formulations, devices and methods to control drug transport into and within the body. These focus areas are intended to broadly encompass topics relevant to pharmaceutical research.  Current CD4 fellows cannot apply for a second consecutive year of support.  Students who were CD4 fellows in years prior to the 2011-2012 academic year are eligible. The primary basis for evaluation of CD4 fellowship applications is (i) demonstrated interest and direct activity in pharmaceutical research, as evidenced by prior and planned activities in the field, (ii) academic credentials, as demonstrated by grades, GRE scores, research and other accomplishments, and (iii) recommendation letters. Applications from all eligible candidates are welcome.  Women and underrepresented minorities are especially encouraged to apply.  

For complete applicant criteria/program information, contact Donna Bondy.

The BioE Program is interdisciplinary in that it is not a standalone academic unit like most departments or schools at Georgia Tech. Rather, 8 different academic units from the Colleges of Engineering and Computing make up the program.

Why did you choose the BioE program?

"I have always been interested in interdisciplinary research with an immediate impact on the well being of others. The BioE program provides me with an ideal platform to pursue my interest in problem solving while not limiting myself to a particular discipline." - Timothy Kassis, School of Electrical and Computer Engineering

"You have more choice in classes and could take more real engineering courses." - Adrian Lam, Wallace H. Coulter Department of Biomedical Engineering

"Flexible classes, more interesting classes. Ability to work with professor outside of BME." - Apoorva Kalasuramath, George W. Woodruff School of Mechanical Engineering

"I needed the BioE Program's course flexibility to match my interdisciplinary research focus. My research does not fit into one specific discipline, and the BioE Program allowed me to create the graduate experience I wanted mixing ME, BME, APPH, and BIO courses and having a committee members from each of these disciplines." - Julia Henkels, George W. Woodruff School of Mechanical Engineering

"I really liked the fact that we are able to choose an advisor from multiple departments. I also liked the fact that the coursework was not restricted to specific classes, but could be tailored to our research areas." - Rachel Simmons, School of Chemical and Biomolecular Engineering

"The BioEngineering program enabled me to have a solid education in the classical engineering disciplines while allowing me to apply those concepts in my medical research." - Jonathan Suever, Wallace H. Coulter Department of Biomedical Engineering What has been your favorite part of the BioEngineering Program?

What has been your favorite part of the BioEngineering Program?

"The interdisciplinary nature of the program where I am continuously challenged. My project involves various areas of the basic sciences in addition to various engineering disciplines. The people in the program are also very accepting and collaboration seems to be a central pivot of the program. There is no shortage of people working together across labs both officially and unofficially." - Timothy Kassis, School of Electrical and Computer Engineering

"Access to a large number of faculty and picking my own classes." - Ivan Caceres, Wallace H. Coulter Department of Biomedical Engineering

"I like the coursework requirements and the flexibility I had in selecting an advisor." - Ashley Allen, Wallace H. Coulter Department of Biomedical Engineering "You get to work with the best in science and engineering, no matter which background you come from." - Rich Hammett, Wallace H. Coulter Department of Biomedical Engineering

"The faculty and my fellow BioEs have made this experience for me. My PhD committee has been an invaluable support to my research, and my fellow BioEs have been with me all the way to commiserate, celebrate, or lend a hand. It's a great community. The people here want to be here, and they want to help you succeed." - Julia Henkels, George W. Woodruff School of Mechanical Engineering

"I think my favorite part has ended up being the very collaborative nature of the BioE program. I feel that I more readily have access to people that do not necessarily have the same background as I do." - Rachel Simmons, School of Chemical and Biomolecular Engineering

Best BioE Ph.D. Thesis
Edward Phelps, Ph.D. - Garcia Lab -  Award Recipient 2012

Best BioE Advisor
Dr. Melissa Kemp, BMED - Award Recipient 2012

To honor these recipients, an awards ceremony will be held Fall semester 2012.

During her visit in February, Boyan met with several congressmen, urging them to reauthorize “The Pediatric Medical Device Safety and Improvement Act." The law provides grants to fund non-profit pediatric device consortia, such as the Atlanta Pediatric Device Consortium. The grants connect scientists and innovators with device manufacturers, providing them financial resources and regulatory guidance needed to advance the development of devices for children.

“The funding from the FDA has opened many doors and some of our small companies have been able to secure venture capital funding to pursue these devices,” Boyan said.

One of three FDA-sponsored consortia awarded last year, the Atlanta Pediatric Device Consortium is a partnership between Georgia Tech, Children’s Healthcare of Atlanta and Emory University.

The Atlanta Pediatric Consortium provides assistance with engineering design, prototype development, pre-clinical and clinical studies and commercialization for novel pediatric medical devices. It is currently composed of nine projects, three main projects and six pilot projects, which were incorporated from the first Pediatric Device Competition.

“This consortium has brought excitement to the Atlanta Community and strengthened our research partnerships to develop the future of pediatric medical devices,” Boyan said.

Passed in 2007, “The Pediatric Medical Device Safety and Improvement Act" includes important incentives that promote the development of medical devices for children, which currently lags five to 10 years behind those for adults. Significant barriers to pediatric device development exist, including physiological differences in pediatric patients and challenges with recruiting pediatric participants for clinical trial. The law helps to support the creation of more pediatric devices, with 107 device projects developed during the program’s first two years, according to a report by the General Accounting Office.

Boyan was accompanied to D.C. by consortium co-directors Kevin Maher, MD, a cardiologist and researcher specializing in pediatrics with appointments at the Children’s Healthcare of Atlanta Sibley Heart Center and Emory University and Wilbur Lam, MD, PhD, a pediatric hematologist/oncologist and bioengineer with appointments at Emory, the Aflac Cancer Center of Children’s Healthcare of Atlanta and Georgia Tech.

The Institute’s College of Engineering ranked No. 4 for theeighth consecutive year and all eleven of the programs within the college areranked in the top 10 including industrial engineering (No. 1), biomedical and bioengineering (No.2), civil (No. 3), aerospace (No. 4), electrical (No. 5), nuclear (No. 5), environmental(No. 6), computer (No. 6), mechanical (No. 6), materials (No. 7) and chemical(No. 10).

“All of Georgia Tech’s graduateengineering programs are ranked in the top ten in the nation.  We’re proud that our College of Engineeringis not only one of the best in the U.S., but also the largest, preparing nearly3,000 graduates each year,” said Georgia Tech President G. P. “Bud”Peterson.  “We commend our outstandingfaculty, staff and students who helped make this a reality.”

Georgia Tech appears on the top 10 list of engineering specialties more than any other ranked institution.

The Georgia Tech College of Management full-time MBA programranked No. 32, while the Institute’s part-time MBA program ranked No. 28.

Georgia Tech researchers are developing new ways to diagnose and treat heart problems -- from advanced imaging techniques and guidance for drug therapies to sophisticated surgical procedures. Georgia Tech’s emphasis on translational research accelerates the pace at which new heart-related discoveries are put to use in patient care.

Improving Heart Surgery

To advance the goal of minimally invasive cardiac surgery, researchers have developed a technology that simplifies and standardizes the technique for opening and closing the beating heart during surgery.

Apica Cardiovascular, a Georgia Tech and Emory University medical device startup, licensed the technology from the two institutions. The firm recently received a $5.5 million investment to further develop the system, which will make the transapical access and closure procedure required for delivering therapeutic devices to the heart more routine for cardiac surgeons. The goal is to expand the use of surgery techniques that are less invasive and do not require stopping the heart.

With research and development support from the Coulter Foundation Translational Research Program and the Georgia Research Alliance, the company has already completed a series of pre-clinical studies to test the functionality of the device and its biocompatibility. James Greene currently serves as the CEO of the company, which has offices in Galway, Ireland, and in Atlanta.

For more information on this work, visit http://gtresearchnews.gatech.edu/apica-cardiovascular/.

Diagnosing Heart Disease

Levent Degertekin is designing tiny devices micromachined from silicon that may make diagnosing and treating coronary artery diseases easier.

Degertekin, the George W. Woodruff Chair in Mechanical Systems, and Paul Hasler, a professor in the School of Electrical and Computer Engineering at Georgia Tech, micromachined intravascular ultrasound imaging arrays with integrated electronics. Placed on catheters inserted into the body, the devices image the arteries of the heart in three dimensions at high resolution using high-frequency ultrasound waves.

The system boasts a more compact design and three-dimensional imaging capability for guiding cardiologists during interventions, such as those for completely blocked arteries. The technology also offers higher resolution than current intravascular ultrasound systems, which help diagnose vulnerable plaque, a leading cause of heart attacks.

Funding for this research currently is provided by the National Institutes of Health. To commercialize the technology, the researchers have formed a startup company called SIBUS Medical, which is receiving assistance from VentureLab, a unit of Georgia Tech’s Enterprise Innovation Institute that nurtures faculty startup companies.

Detecting and Treating Atherosclerosis

With a five-year $14.6 million contract from the National Institutes of Health (NIH), Georgia Tech and Emory University researchers are developing nanotechnology and biomolecular engineering tools and methodologies for detecting and treating atherosclerosis. The award supports the interdisciplinary Center for Translational Cardiovascular Nanomedicine, which is led by Gang Bao, the Robert A. Milton Chair in Biomedical Engineering in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Atherosclerosis typically occurs in branched or curved regions of arteries where plaques form because of cholesterol build-up. Inflammation can alter the structure of plaques so they become more likely to rupture, potentially causing a blood vessel blockage and leading to heart attack or stroke.

The researchers are working to accomplish four goals:

• Using nanoparticle probes to image and characterize atherosclerotic plaques
• Diagnosing cardiovascular disease from a blood sample
• Designing new methods for delivering anti-atherosclerosis drugs and genes into the body
• Developing stem cell based therapies to repair damaged heart tissue

Additional researchers from the Coulter Department and from Emory University are also contributing to the project. For more information on this work, visit http://gtresearchnews.gatech.edu/cardiovascular-nanomedicine-center/.

Improving Drug Dosing Following a Heart Attack

A research team led by Georgia Tech mechanical engineering assistant professor Craig Forest is designing a device to quickly and accurately personalize a patient’s drug dosage to prevent blood clots that can cause heart attacks.

When someone experiencing heart attack symptoms arrives at an emergency room, he or she typically receives a standard dose of aspirin and/or clopidogrel to prevent further blood clotting. But that standard dose may not be the best dose for a given individual.

With Forest’s device, a small blood sample is sent through a microchip containing a network of microfabricated capillaries that mimic the branching coronary arteries around the human heart. Because the branches contain flow restrictions of different sizes, the failure of blood to flow through the branches with smaller restrictions indicates that a higher drug dose may be required.

Determining the necessary dose of anti-clotting drugs can be difficult. Too much of the drug may cause the patient to experience gastrointestinal bleeding. Too little drug may allow additional clot formation and set the stage for another heart attack. Forest’s device should help determine the right dosage for each patient.

Emory University Department of Emergency Medicine assistant professor Jeremy Ackerman and Georgia Tech Regents’ professor of mechanical engineering David Ku are working with Forest on this project, which is supported by the American Heart Association.

Examining Heart Valve Leakage

An estimated 1.6 million Americans suffer moderate to severe leakage through their tricuspid valve, a complex structure that closes off the heart’s right ventricle from the right atrium. If left untreated, severe leakage can affect an individual’s quality of life and can even lead to death.

Research teams led by Ajit Yoganathan, Georgia Tech Regents’ professor and Wallace H. Coulter Distinguished Faculty Chair in Biomedical Engineering, have discovered causes for the tricuspid valve’s leakage and ways to predict the severity of leakage in the valve. These study results could lead to improved diagnosis and treatment of the condition.

A study published in the journal Circulation found that either dilating the tricuspid valve opening or displacing the papillary muscles that control its operation can cause the valve to leak. A combination of the two actions can increase the severity of the leakage, which is called tricuspid regurgitation.

Standard clinical procedures that detail when and how tricuspid valve repairs should be performed need to be developed and this study suggests several items that should be considered in developing those protocols, according to the researchers.

In another study published in the journal Circulation: Cardiovascular Imaging, researchers found that the anatomy of the heart’s tricuspid valve can be used to predict the severity of leakage in the valve. Using 3-D echocardiograms from 64 individuals who exhibited assorted grades of tricuspid leakage, the researchers found that pulmonary arterial pressure, the size of the valve opening and papillary muscle position measurements could be used to predict the severity of an individual’s tricuspid regurgitation.

The study will change the focus and direction of future surgical therapies for tricuspid regurgitation to make them better and more durable, the researchers said.

Researchers from the Coulter Department, Emory University, Children’s Hospital Boston and Mount Sinai Medical Center contributed to these two studies.

For more information on this work, visit http://gtresearchnews.gatech.edu/tricuspid-valve-leakage/ and http://gtresearchnews.gatech.edu/tricuspid-regurgitation/. 

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Additionally, the new BBUGS website has incorporated a message board whereby BBUGS members can post announcements pertaining to job openings, scholarship/grant availabilities, seminars/workshops or upcoming social activities. The new website design includes new and improved functionality to make navigation throughout the website less complicated and more manageable.

BBUGS is currently the largest, most diverse, graduate student group on the Georgia Tech campus and is an interdisciplinary student group, comprised of 8 different departments, with their home in the Parker H. Petit Institute for Bioengineering and Bioscience. Comprised of over 500 members, BBUGS serves as the core student group for the bioengineering and bioscience community and is open to all Georgia Tech and Emory University students from bio-related fields.  Existing members are encouraged to go to the new website and create a profile to stay engaged. 

Thescientists showed for the first time how the virus called “Lambda” evolved tofind a new way to attack host cells, an innovation that took four mutations toaccomplish. This virus infects bacteria, in particular the common E. coli bacterium. Lambda isn’tdangerous to humans, but this research demonstrated how viruses evolve complexand potentially deadly new traits, said Justin Meyer, MSU graduate student, whoco-authored the paper with Richard Lenski, MSU Hannah Distinguished Professorof Microbiology and Molecular Genetics.

“Wewere surprised at first to see Lambda evolve this new function, this ability toattack and enter the cell through a new receptor­ – and it happened so fast,”Meyer said. “But when we re-ran the evolution experiment, we saw the same thinghappen over and over.”

Thispaper comes on the heels of news that scientists in the U.S. and theNetherlands produced a deadly version of bird flu. Even though bird flu is amere five mutations away from becoming transmissible between humans, it’shighly unlikely the virus could naturally obtain all of the beneficialmutations all at once. However, it might evolve sequentially, gaining benefitsone-by-one, if conditions are favorable at each step, he added.

Throughresearch conducted at BEACON, MSU’s National Science Foundation Center for theStudy of Evolution in Action, Meyer and his colleagues’ ability to duplicatethe results implied that adaptation by natural selection, or survival of thefittest, had an important role in the virus’ evolution.

Whenthe genomes of the adaptable virus were sequenced, they always had fourmutations in common.

“Theparallelism shown in the evolutionary history of adaptable viruses was strikingand was far beyond what is expected by chance,” noted paper co-author Joshua Weitz, anassistant professor in the School ofBiology at Georgia Tech.

Incontrast, the viruses that didn’t evolve the new way of entering cells had someof the four mutations but never all four together, said Meyer, who holds theBarnett Rosenberg Fellowship in MSU’s College of Natural Science.

“Inother words, natural selection promoted the virus’ evolution because themutations helped them use both their old and new attacks,” Meyer said. “Thefinding raises questions of whether the five bird flu mutations may also havemultiple functions, and could they evolve naturally?”

Additionalauthors of the paper include Devin Dobias, former MSU undergraduate (now agraduate student at Washington University in St. Louis); Ryan Quick, MSUundergraduate; and Jeff Barrick, a former Lenski lab researcher now on thefaculty at the University of Texas at Austin.

Fundingfor the research was provided in part by the National Science Foundation,Defense Advanced Research Projects Agency, James S. McDonnell Foundation andBurroughs Wellcome Fund.

This research was supported in part bythe Defense Advanced Research Projects Agency (DARPA) (Award No.HR0011-09-1-0055) and the National Science Foundation (NSF). The content issolely the responsibility of the principal investigator and does notnecessarily represent the official views of DARPA or NSF.

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Writer: Layne Cameron

“Given that breast cancer is the most common cancer in U.S. women and the second leading cause of cancer death, many people could benefit from the development of effector nanoclusters,” Champion says. “This work validates the idea of using bacterial proteins for therapeutic applications and the concept can be expanded for a variety of drug development and delivery needs for other diseases.”

A select group of bacterial pathogens secrete proteins called effectors during infection, which enable them to survive and grow in a hostile host. Some of these effectors have the capability to interfere with the same pathways that are altered in breast cancer.

“The goal of my research is to use these effector proteins as novel breast cancer therapies,” Champion says. “In order for these proteins to be used as anticancer drugs, the normal bacterial delivery mechanisms must be replaced by a drug delivery system able to deliver biologically active protein to breast cancer cells.” 

To engineer this modified drug delivery system, the effector proteins must be linked together into nano-sized clusters that can enter breast cancer cells and then fall apart to allow the individual proteins to act inside the cells. By fabricating effector nanoclusters, Champion will be able to access their ability to restore normal behaviors in breast cancer cells, such as increased apoptotic cell death, decreased proliferation, decreased metastasis, and increased sensitivity to chemotherapeutics.

After receiving her PhD from the University of California, Santa Barbara in 2007, Champion completed a postdoctoral appointment as a National Institutes of Health Postdoctoral Fellow at the California Institute of Technology. She joined the faculty at Georgia Tech in 2009, where she focuses her research on protein engineering strategies to synthesize novel materials capable of specific interactions with cells or other proteins. The overall goal of her research is to reverse disease through interference with inflammatory pathways or promotion of healing mechanisms.

This project was supported by the National Science Foundation (NSF) (Award No. DMR-1105248). The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NSF.

The Atlanta-based startup, Clearside Biomedical, plans to develop microinjection technology that will use hollow microneedles to precisely target therapeutics within the eye. If the technique proves successful in clinical trials and wins regulatory approval, it could provide an improved method for treating diseases that affect the back of the eye, including age-related macular degeneration.

The technology was developed in collaboration between the research groups of Mark Prausnitz, a Regents' professor in Georgia Tech's School of Chemical and Biomolecular Engineering, and Henry Edelhauser, a professor in the Department of Ophthalmology at Emory School of Medicine. Research leading to development of the technology was sponsored by the National Institutes of Health (NIH).

"We expect that targeting drug delivery within the eye will be helpful because we should be able to concentrate drugs at the disease sites where they need to act, and keep them away from other locations," said Prausnitz. "This could reduce side effects and possibly also decrease the dose required."

Prior to this development, drugs could be delivered to the retinal tissues at the back of the eye in three indirect ways: (1) injection by hypodermic needle into the eye's vitreous humor, the gelatinous material that fills the eyeball, (2) eye drops, which are limited in their ability to reach the back of the eye, and (3) pills taken by mouth that expose the whole body to the drug.

The technology developed by Georgia Tech and Emory uses a hollow micron-scale needle to inject therapeutics into the suprachoroidal space located between the outer surface of the eye -- known as the sclera -- and the choroid -- a deeper layer that provides nutrients to the rest of the eye. Preclinical research has demonstrated that fluid can flow between the two layers, where it can spread out to the entire eye, including structures such as the retina that are now difficult to reach.

By targeting this suprachoroidal space using microscopic needles, the researchers believe they can reduce trauma to the eye, make drugs more effective and reduce complications. The new delivery method could help advance a new series of drugs being developed to target the retina, choroid and other structures in the back of the eye.

"This is a significant advance in the field of ophthalmology," said Edelhauser. "Until now, it has been difficult to target drug delivery to specific locations within the eye. This new microneedle technology enables precise drug targeting to the suprachoroidal space and other locations within the eye."

In research reported in the January 2011 issue of the journal Pharmaceutical Research, the Georgia Tech-Emory team demonstrated for the first time that this technique can be used to deliver nanoparticles and microparticles to specific parts of the eye. In later research, they also showed that microneedle injections into the suprachoroidal space rapidly resulted in concentrations of drugs and particles that could be maintained for several months.

Between two and three million eye injections are made each year, many of them to treat age-related macular degeneration (AMD). The researchers believe that the microneedle-based technique could be useful for treating both AMD and glaucoma, as well as other ocular conditions related to diabetes.

The $4 million in funding for Clearside Biomedical will come from Hatteras Venture Partners, a venture capital firm based in Research Triangle Park, N.C. Hatteras focuses on seed and early-stage investments in companies developing products in biopharmaceutical, medical device, diagnostic and related human health areas.

"Clearside Biomedical represents an ideal fit for Hatteras Discovery as the platform technology is highly innovative, based on elegant science and the lead product is expected to be in clinical trials in the United States in less than 18 months," said Christy Shaffer, Ph.D., venture partner and managing director of the Hatteras Discovery Fund.

So far, the technique has been tested only in animals. The Hatteras funding will allow the company to conduct additional efficacy and safety testing needed to seek regulatory approval. The company's first product is expected to address macular edema and retinal vein occlusion.

Clearside was formed with the assistance of Georgia Tech's VentureLab program, which helped obtain early-stage seed funding from the Georgia Research Alliance. Georgia Tech VentureLab also helped the founders connect with the company's president and CEO, Daniel White, a veteran ophthalmic entrepreneur. Before joining Clearside, White was a co-founder of Alimera Sciences, an Atlanta company that is developing ophthalmic pharmaceuticals.

Two researchers from the Prausnitz lab who have been involved in development of the ocular drug delivery technique will also join the company. They are Samirkumar Patel, a postdoctoral researcher and Vladimir Zarnitsyn, a research scientist.

Research leading to the development of the technology has been supported by the National Institutes of Health (NIH). The content of this article is solely the responsibility of the principal investigators and does not necessarily represent the official view of the NIH.

Henry Edelhauser, Samirkumar Patel, Mark Prausnitz, Vladimir Zarnitsyn, Emory University and Georgia Tech have financial interests in Clearside Biomedical and its ocular platform. Edelhauser, Patel, Prausnitz and Zarnitsyn own equity in Clearside and the terms of this arrangement have been reviewed and approved by Emory University or Georgia Tech in accordance with their conflict of interest policies.

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Writer: John Toon

Three of the new AAAS Fellows at Georgia Tech hail from the College of Engineering and one is on the faculty in the College of Computing. The Fellows were announced today in the journal Science and will be honored at the Fellows Forum, held Feb. 18 at the AAAS Annual Meeting in Vancouver, Canada.

The new AAAS Fellows at Georgia Tech are:

Ali Adibi, professor of electrical and computer engineering, who was honored for his “distinguished contributions to the fields of integrated nanophotonics, photonic crystals, and volume holography."

David Bader, professor of computational science and engineering in the College of Computing, who earned the distinction for “distinguished contributions to the field of computational science and engineering.”

Robert Butera, professor of electrical and computer engineering who also holds a joint appointment in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, was named Fellow “for advances in computational neuroscience and neurotechnology, promoting engineering through society, editorial, and university leadership, and contributing to STEM policy and educational initiatives."

Paul Steffes, professor of electrical and computer engineering, who earned the distinction for “contributions to the understanding of planetary atmospheres through innovative microwave measurements."

AAAS is an international non-profit organization dedicated to advancing science around the world by serving as an educator, leader, spokesperson and professional association. AAAS publishes the journal Science as well as many scientific newsletters, books and reports, and spearheads programs that raise the bar of understanding for science worldwide. The four Georgia Tech faculty members were among 539 Fellows elected by the AAAS Council in November. 

Bellamkonda directs the Neurological Biomaterials and Cancer Therapeutics Laboratory, a part of the Laboratory for Neuroengineering in the joint Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. He also serves as associate vice president within the Office of the Executive Vice President for Research (EVPR), directs a T32 training grant called Rational Design of Biomaterials, directs a Graduate Leadership Program for BioE/BME graduate students and is a Georgia Cancer Coalition Distinguished Scholar.  

Current research projects in the Neurological Biomaterials and Cancer Therapeutics Laboratory include: developing scaffolds for peripheral nerve regeneration and interfacing; developing vehicles for contrast agents and receptor-targeted nano-scale drug delivery for the treatment of malignant tumors; and engineering a system for tumor exvasion. He is also leading a research team exploring interfacing technologies that will better integrate external electronics to the nervous system. In addition to the Flanagan endowment, Bellamkonda’s research is funded by grants from NIH, NSF, the Coulter Foundation, the Georgia Cancer Coalition, and Ian's Friend's Foundation.

A new five-year grant of $1.6 million from the National Institutes of Health will create a training center in computational neuroscience, one of only five national training centers supported by the NIH through its NIH Blueprint training grant program.

The grant is entitled “From cells to systems and applications: computational neuroscience training at Emory and Georgia Tech.” Principal investigators are Dieter Jaeger, PhD, professor of biology, Emory University and Garrett Stanley, PhD, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. 

“The NIH Blueprint training grants are particularly innovative in that they combine undergraduate and graduate training programs and provide trainee support at both levels,” says Jaeger. “This is a mission that is highly synergistic with the training mission at Emory and Georgia Tech.”

The NIH Blueprint is a framework to enhance cooperative activities among 16 NIH Institutes, Centers, and Offices that support research on the nervous system.

The core training group will initially consist of 16 faculty members from departments spanning Emory University School of Medicine (physiology, neurology, anesthesiology, biomedical engineering) and Emory College of Arts and Sciences (biology, psychology) as well as Georgia Tech (biomedical engineering, electrical engineering)

“This impressive range of faculty and departments provides testimony to the highly collaborative and interdisciplinary nature of this field of study at Georgia Tech and Emory,” notes Stanley.

The training grant funds students in the Emory Neuroscience Program and the joint Emory/Georgia Tech BME PhD program, and undergraduates on both campuses.

The five-year project focuses on developing biomaterials capable of capturing certain molecules from embryonic stem cells and delivering them to wound sites to enhance tissue regeneration in adults. By applying these unique molecules, clinicians may be able to harness the regenerative power of stem cells while avoiding concerns of tumor formation and immune system compatibility associated with most stem cell transplantation approaches.

"Pre-clinical and clinical evidence strongly suggests that the biomolecules produced by stem cells significantly impact tissue regeneration independent of differentiation into functionally competent cells," said Todd McDevitt, director of the Stem Cell Engineering Center at Georgia Tech and an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "We want to find out if the signaling molecules responsible for scarless wound healing and functional tissue restoration during early stages of embryological development can be used with adult wounds to produce successful tissue regeneration without scar formation."

In addition to McDevitt, Coulter Department associate professor Johnna Temenoff and Woodruff School of Mechanical Engineering professor Robert Guldberg are also investigators on the project.

Regenerative medicine seeks to restore normal structure and function to tissues compromised by degenerative diseases and traumatic injuries. The contrast between embryonic and adult wound healing suggests that molecules that facilitate tissue regeneration during embryonic development are distinctly different from those of adult tissues.

This grant includes plans for engineering biomaterials that can efficiently capture morphogens, which are molecules secreted by embryonic stem cells undergoing differentiation. The study will also evaluate the regenerative activity of molecule-filled biomaterials in animal models of dermal wound healing, hind limb ischemia and bone fractures. Examining the effects of the morphogens on a range of animal wound models will increase the likelihood of success and define any limitations of the technology, such as its use for specific tissues or injuries.

"Biomaterials have largely been used in an attempt to direct stem cell differentiation or serve as passive cell transplantation vehicles for regenerative medicine and tissue engineering purposes," said McDevitt, who is also a Petit Faculty Fellow in the Institute for Bioengineering and Bioscience at Georgia Tech. "The idea of specifically engineering biomaterial properties to capture and deliver complex assemblies of stem cell-derived morphogens without transplanting the cells themselves represents a novel strategy to translate the potency of stem cells into a viable regenerative medicine therapy."

The award was one of 17 granted this year through the NIH Director's Transformative Research Projects Program (T-R01), which was created to challenge the status quo with innovative ideas that have the potential to advance fields and speed the translation of research into improved health for the American public.

Another T-R01 grant was awarded to Coulter Department professor Shuming Nie, associate professor May Wang and University of Pennsylvania School of Medicine Thoracic Surgery Research Laboratory director Sunil Singhal. That $7 million, five-year grant will support continuing work by the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology team on developing fluorescent nanoparticle probes that hone in on cancer cells and on creating instruments that visualize them for cancer detection during surgery.

Since its inception in 2009, the NIH Director's Award Program has funded a total of 406 high-risk research projects, including 79 T-R01 awards.

"The NIH Director's Award programs reinvigorate the biomedical work force by providing unique opportunities to conduct research that is neither incremental nor conventional," said James M. Anderson, director of the Division of Program Coordination, Planning and Strategic Initiatives, who guides the NIH Common Fund's High-Risk Research program. "The awards are intended to catalyze giant leaps forward for any area of biomedical research, allowing investigators to go in entirely new directions."

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For the fourth consecutive year,Georgia Tech was also one of 16 schools included on the Princeton Review’s GreenRating Honor Roll, a measure of how environmentally friendly institutions areon a scale of 60 to 99. The Institute, the only Georgia college included on thelist, received thehighest possible score (99).

The annualcollege rankings are based on a survey of 122,000 students at 376 top colleges.The 80-question survey asked students about their experiences on topics fromcareer services to housing.

The fourth annual Green Ratingwas based primarily on institutional data collected during 2010-2011.  For example, Georgia Tech hasapproximately 100classes that include significant sustainability components and maintainsnumerous Institutional environmental sustainability programs ranging fromrecycling to green cleaning practices.

Sustainability is also a keycomponent of the Institute’s Campus Master Plan and Landscape Master Plan. InFebruary, the Arbor Day Foundation recognized Georgia Tech as a 2011 TreeCampus USA school for the third consecutive year for its dedication to campusforestry management and environmental stewardship.

The magazine collected median pay figures from two pools of alumni, recentgrads and those alums 15 years out from obtaining their degrees. This wascompared with the actual cost of tuition. From this information, SmartMoneycreated a "Payback Score," reflecting an actual return on tuitioninvestment.

“A Georgia Techeducation is the investment of a lifetime for our graduates,” said Georgia TechPresident G. P. “Bud” Peterson. “As innovators and leaders in business,industry and government, Tech alumni are developing solutions to some ofsociety’s most pressing challenges, which benefit our state and our nation.”

According to the survey, Georgia Tech graduates paid $87,810 in tuition,receiving a median salary of $57,300. Based on this data, the payback score wasdetermined to be 221. This score compared with the University of Texas, Austin,which placed second with a payback score of 194.
For the complete list, please visit the SmartMoney website