The paper, The Borderlands of Foldability: Lessons from Simplified Proteins, is a meta-analysis of six decades of protein research and reveals that ancient proteins may have been far more complicated and dynamic than previously thought.
Recently published in the journal Trends in Chemistry, the study includes Georgia Tech researchers Lynn Kamerlin, professor in the School of Chemistry and Biochemistry and Georgia Research Alliance Vasser-Woolley Chair in Molecular Design, and Quantitative Biosciences Ph.D. candidate Alfie-Louise Brownless.
Co-authors also include Institute of Science Tokyo graduate student Koh Seya and Liam M. Longo, who serves as a specially appointed associate professor at Science Tokyo and as an affiliate research scientist at the Blue Marble Space Institute of Science.
The research has implications ranging from the origins of life and the search for life in the universe to cutting-edge medical innovation. “One of the biggest unanswered questions in science is how life first began,” says Kamerlin, who is a corresponding author of the study. “Understanding how the first protein-like molecules formed and what the earliest proteins may have been like is a key part of that puzzle.”
“Proteins power our bodies — and all life on Earth,” she adds. “Simply put, the evolution of proteins is the reason that we’re able to have this conversation at all.”
If proteins are the scaffolding of life, amino acids are the components that make up that scaffolding. “Today, an average protein is constructed from a chain of about 300 amino acids, involving 20 different types of amino acids,” Kamerlin shares. Proteins fold when these chains twist into a specific 3-dimensional shape, creating structures critical for biology.
However, while these folds are essential, exactly how a protein knows which way to fold remains a mystery. “We know that proteins didn’t just fold randomly,” Kamerlin shares, “because randomly trying all possible configurations would take a protein longer than the age of the universe.”
It’s a cornerstone problem in biological science called “Levinthal’s Paradox,” and highlights a fundamental mystery: Proteins fold incredibly quickly into very specific combinations — but like a sheet of paper spontaneously folding into an origami swan, researchers don’t know how proteins “choose” the folds they make.
“We can predict what a protein will look like, but can’t tell you how it got there,” Kamerlin adds. “That’s what we’re interested in exploring: how small early proteins developed into the complex proteins that support every living thing on today’s Earth.”
Early proteins likely had access to just half of today’s amino acids. “About 10-12 amino acids were likely available on early Earth,” Kamerlin says. Like writing a story with just the letters “A” through “L,” researchers assumed that the ‘vocabulary’ proteins could build from such a limited amino acid alphabet would also be constrained.
“There is a language to protein folding,” Kamerlin explains. “That language is hidden in their structures. Our research is in trying to understand the rules — the grammar and vocabulary that dictate a protein fold.”
The grammar they discovered was surprising: with a combination of creative techniques and environmental support, complex structures can arise from limited amino acid alphabets.
“We found that it is possible to develop complex folds with very simple tools — and certain environments, like salty ones, can help support that,” Kamerlin shares. “Early proteins could also cross-link and associate, interacting like LEGO blocks to create more complex structures.”
Now, the team is conducting research in environments that could mimic conditions on early Earth — aiming to discover more about how these regions could have given rise to today’s complex proteins. “This aspect of our research also ties into the amazing space research happening at Georgia Tech,” Kamerlin says. “While we’re interested in understanding early life on Earth, our work could help inform where best to look for evidence of life beyond our planet.”
Kamerlin specializes in creating computer models that simulate possible scenarios – creating an opportunity to quickly and efficiently test many theories. The most compelling of these can then be tested by her collaborator and co-author at Science Tokyo, Liam Longo, in lab experiments.
Protein folding is also at the forefront of medical innovation, ranging from diagnostic tools to cancer treatments and neurodegenerative diseases. “In the broader scope, we’re interested in discovering what we can design, what we can stress test, and what we can reconstruct with AI and other computational tools,” Kamerlin says. “Because if you can understand how proteins fold, you gain the ability to design them.”
Funding: NASA, the Human Frontier Science Program, and the Knut and Alice Wallenberg Foundation
DOI: https://doi.org/10.1016/j.trechm.2026.03.001
]]>Selena Langner
College of Sciences
Georgia Institute of Technology
Published today in the journal Nature Communications, the paper “Trivalent Titanium in High-Titanium Lunar Ilmenite” confirms titanium in a reduced, trivalent state in a black, metal-rich lunar mineral called ilmenite. It’s a state only possible in low-oxygen environments, conditions researchers refer to as “reducing.”
“Models have suggested that these reducing conditions may have varied at different locations and times across the surface of the Moon,” says lead author Advik Vira, a graduate student in the School of Physics who recently earned his doctoral degree. “We hope our microscopy technique can be a valuable step in mapping and understanding the Moon’s 4.5-billion-year history.”
The team anticipates that their technique could be used on many of the lunar samples collected more than 50 years ago by the Apollo missions in addition to the Apollo Next Generation Samples — a group of lunar samples that have been stored under pristine conditions — and new samples from the planned Artemis missions, with Artemis II slated for launch this spring. The technique might also be applicable to samples collected from the far side of the Moon and returned in 2024 by the Chang’e-6 mission.
“The Moon holds clues not only to its own past, but also to the earliest eras of Earth’s evolution — history that has long since been erased from our planet,” Vira says. “This study is a step toward understanding the history of both and a reminder that there is still so much left to learn from the lunar rocks we’ve brought back to Earth.”
The School of Physics research team included corresponding authors Vira and Professor Phillip First; in addition to graduate student Roshan Trivedi; undergraduate students Gabriella Dotson, Keyes Eames, Dean Kim, and Emma Livernois; and Professor Zhigang Jiang, along with Institute for Matter and Systems Materials Characterization Facility Senior Research Scientist Mengkun Tian; School of Chemistry and Biochemistry Senior Research Scientist Brant Jones and Thom Orlando, Regents' Professor in the School of Chemistry and Biochemistry with a joint appointment in the School of Physics.
The Georgia Tech team was joined by Addis Energy Senior Geochemist Katherine Burgess; Macalester College Assistant Professor of Geology Emily First; along with Lawrence Berkeley National Laboratory Research Scientist Harrison Lisabeth, Senior Scientist Nobumichi Tamura, and Postdoctoral Fellow Tyler Farr, who recently earned a Ph.D. from Georgia Tech’s George W. Woodruff School of Mechanical Engineering.
The investigation began with a dark gray rock called a lunar basalt. Formed when ancient magma erupted on the Moon’s surface, minerals crystallized as it cooled — preserving key information in their structures. Billions of years later, the rock was brought to Earth by the 1972 Apollo 17 mission, where a small piece is now stored at Georgia Tech’s Center for Lunar Environment and Volatile Exploration Research (CLEVER), a NASA Solar System Exploration Research Virtual Institute (SSERVI) center led by Orlando.
As a NASA virtual institute, CLEVER supports researchers exploring lunar conditions and developing tools for the upcoming crewed Artemis missions, and provided the lunar samples for this research. The SSERVI also plays a critical role in training the next generation of planetary researchers: both Vira and Farr earned their Ph.D.s while on the CLEVER team.
“At CLEVER, we are very interested in understanding the impacts of space weathering,” Vira says. “We implemented modern sample preparation and advanced microscopy techniques to image samples at the atomic level, and were curious to apply it more broadly to the collection of Apollo rocks in the Orlando Lab. This sample caught our attention.”
“When we imaged an ilmenite crystal from the lunar basalt, what struck us first was how uniform and perfect the crystal structure was,” he recalls. “We found no defects from space weathering and instead saw an undamaged, pristine crystal — undisturbed for 3.8 billion years.”
To investigate further, the team analyzed small chips of the rock with Burgess, a member of the RISE2 SSERVI team and then a geologist at the U.S. Naval Research Laboratory. Using state-of-the-art electron microscopy and spectroscopy techniques, Vira determined the oxidation state of the elements in the ilmenite present.
In spectroscopy measurements, each element leaves a distinct ‘signature,’ Vira explains. “When we brought our results back to Georgia Tech’s Materials Characterization Facility, Mengkun (Tian) noticed something unusual: the signature showed titanium might be present in the trivalent state.”
The presence of trivalent titanium had long been suspected in this lunar mineral. The team was intrigued.
With funding from Georgia Tech’s Center for Space Technology and Research (CSTAR), Vira returned to the U.S. Naval Research Laboratory to analyze additional samples. The results confirmed that more titanium was present than the mineral’s formula (FeTiO₃) predicts — indicating a portion of the titanium present was trivalent.
“That led me to place our measurements in terms of the broader geological context,” Vira shares. Working with First, Vira explored how ilmenite with trivalent titanium could help reconstruct the nature of ancient magmas from the Moon, especially the chemical availability of oxygen.
“Because its location on the Moon was noted during the Apollo mission, we know exactly where this rock is from, and we can determine how old the rock is,” he explains. “When coupled with our trivalent titanium measurements, we can use that information to estimate the reducing conditions for this specific region at the specific time our rock formed.”
If the upcoming Artemis missions return samples suitable for the team’s technique, these rocks could provide a new window into ancient lunar geology. The research also highlights that many lunar samples already on Earth could be reexamined to look for trivalent titanium.
“There is still so much to learn from the lunar samples we have already brought to Earth,” Vira says. “It’s a testament to the long-term value of each sample return mission. As technology continues to advance, this type of work will continue to give us critical insights into our planet and our place in the universe for years to come.”
DOI: 10.1038/s41467-026-69770-w
Funding: This work was directly supported by the NASA SSERVI under CLEVER. Researchers were also supported by the NASA RISE2 SSERVI and the Heising-Simons Foundation. Funding for collaborations between the U.S. Naval Research Laboratory and Georgia Tech for the investigation of lunar minerals was provided by the Georgia Tech Center for Space Technology and Research. Sample preparation was performed at the Georgia Tech Institute for Matter and Systems, which is supported by the National Science Foundation. This work utilized the resources of the Advanced Light Source, a user facility supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, and was supported in part by previous breakthroughs obtained through the Laboratory Direct.
]]>Selena Langner
College of Sciences
Georgia Institute of Technology
Amino acids also play a critical role commercially where they are manufactured and added to pharmaceuticals, dietary supplements, cosmetics, animal feeds, and industrial chemicals — an energy-intensive process leading to greenhouse gas emissions, resource consumption, and pollution.
A landmark new system developed at Georgia Tech could lead to an alternative: a commercially scalable, environmentally sustainable method for amino acid production that is carbon negative, using more carbon than it emits.
The breakthrough builds on a method that the team pioneered in 2024 and solves a key issue – increasing efficiency to an unprecedented 97% and reducing the bioprocess cost by over 40%. It’s the highest reported conversion of CO2 equivalents into amino acids using any synthetic biology system to date.
Published in the journal ACS Synthetic Biology, the study, “Cell-Free-Based Thermophilic Biocatalyst for the Synthesis of Amino Acids From One-Carbon Feedstocks,” was led by Bioengineering Ph.D. student Ray Westenberg and Professor Pamela Peralta-Yahya, who holds joint appointments in the School of Chemistry and Biochemistry and School of Chemical and Biomolecular Engineering. The team also included Shaafique Chowdhury (Ph.D. ChBE 25) and Kimberly Wennerholm (ChBE 23); alongside University of Washington collaborators Ryan Cardiff, then a Ph.D. student and now a Chain Reaction Innovations Fellow at Argonne National Laboratory, and Charles W. H. Matthaei Endowed Professor in Chemical Engineering James M. Carothers; in addition to Pacific Northwest National Laboratory Synthetic Biology Team Leader Alexander S. Beliaev.
"This work shifts the narrative from simply reducing carbon emissions to actually consuming them to create value,” says Peralta-Yahya. “We are taking low-cost carbon sources and building essential ingredients in a truly carbon-negative process that is efficient, effective, and scalable.”
The work builds on the cell-free technology the team used in their earlier study. “Previously, we discovered that a system that uses the machinery of cells, without using actual living cells, could be used to create amino acids from carbon dioxide,” Peralta-Yahya explains. “But to create a commercially viable system, we needed to increase the system’s efficiency and reduce the cost.”
The team discovered that bits of leftover cells were consuming starting materials, and — like a machine with unnecessary gears or parts — this limited the system’s efficiency. To optimize their “machine,” the team would need to remove the extra background machinery.
"Leftover cell parts were using key resources without helping produce the amino acids we were looking for,” says Peralta-Yahya. “We knew that heating the system could be one way to purify it because heat can denature these components.”
The challenge was in how to protect the essential system components from the high temperatures, she adds. “We wondered if introducing enzymes produced by a heat-loving bacterium, Moorella thermoacetica, might protect our system, while still allowing us to denature and remove that inefficient background machinery.”
The results were astounding: after introducing the enzymes, heating and “cleaning” the system, and letting it cool to room temperature, synthesis of the amino acids serine and glycine leaped to 97% yield — nearly three times that of the team’s previous system.
To make the system viable for large-scale use, the team also needed to reduce costs. “One of the most costly components in this system is the cofactor tetrahydrofolate (THF),” Peralta-Yahya shares. “Reducing the amount of THF needed to start the process was one way to make the system more inexpensive and ultimately more commercially viable.”
By linking reaction steps so waste from one step fueled the next, the team devised a method to recycle THF within the system that reduces the amount of THF needed by five-fold — lowering bioprocessing costs by 42%.
“This decrease in cost and increase in yield is a critical step forward in creating a method with real potential for use in industry and manufacturing,” Peralta-Yahya says. “This system could pave the way for moving this carbon-negative technology out of the lab and onto the continuous, industrial scale."
Funding: The Advanced Research Project Agency-Energy (ARPA-E); U.S. Department of Energy; and the U.S. Department of Energy, Office of Science, Biological and Environmental Research Program.
DOI: https://doi.org/10.1021/acssynbio.5c00352
]]>Selena Langner
College of Sciences
Georgia Institute of Technology
The project, inspired by an Atlanta Science Festival event hosted by School of Chemistry and Biochemistry Assistant Professor Andrew McShan, develops an innovative outreach and teaching module around nuclear magnetic resonance (NMR) techniques, and is designed for easy adoption in introductory chemistry and biochemistry courses.
Published earlier this year in the Journal of Chemical Education, the study, “Automated Chemical Profiling of Wine by Solution NMR Spectroscopy: A Demonstration for Outreach and Education” was led by a team from the School of Chemistry and Biochemistry including lead author McShan, Ph.D. students Lily Capeci, Elizabeth A. Corbin, Ruoqing Jia, Miriam K. Simma, and F. N. U. Vidya, Academic Professional Mary E. Peek, and Georgia Tech NMR Center Co-Directors Johannes E. Leisen and Hongwei Wu.
“NMR is one of the most widely used analytical tools in chemistry and the life sciences, and Georgia Tech hosts one of the most cutting-edge NMR centers in the world,” McShan says. “Our study shows that you don’t need advanced training to appreciate how powerful tools like NMR work and how those tools are used in research.”
All materials, tutorials, and data are freely available via online tutorials and a YouTube video, enabling educators to replicate or adapt the activity even in settings with limited access to NMR facilities.
From families with K-12 students to undergraduates to adults with no prior chemistry experience, nearly 130 visitors explored wine chemistry at the Georgia Tech NMR Center during the Atlanta Science Festival event. With McShan’s guidance, they identified and quantified more than 70 chemical components that influence wine taste, aroma, and quality by analyzing the chemical composition, structure, and dynamics of molecules.
Taking on the role of wine investigators (a real-world application of NMR), the group investigated examples of wine fraud, learning to identify harmful additives like methanol, antifreeze, and lead acetate – additives that played roles in both historical and modern wine scandals.
“By connecting the science to something familiar like wine, we were able to spark curiosity and excitement across age groups,” says McShan. “This a framework for how complex analytical techniques can be made inclusive, interactive, and inspiring whether in the classroom or at a science festival.”
The study underscores the potential of NMR and other powerful technologies as outreach opportunities – from engaging the public to better teaching undergraduate students.
“After the event, adults said they learned how chemical composition affects wine characteristics and how NMR is used in research and industry,” McShan says. “Younger participants learned key concepts about wine composition and found benefits from the sensory elements, like watching the spectrometer in action.”
They aim to use these takeaways to continue developing outreach tools. “My end goal is to develop NMR into a practical teaching tool by grounding the technique in real-world examples,” adds McShan. “Using this approach is a clear avenue to introducing the general public to the world-class instruments used by researchers at Georgia Tech and exposing undergraduate students to the powerful analytical techniques they are likely to encounter throughout their careers.”
Funding: National Science Foundation
]]>When centimeter-long aquatic worms, such as T. tubifex or Lumbriculus variegatus, are placed in a Petri dish filled with sub-millimeter sized sand particles, something surprising happens. Over time, the worms begin to spontaneously clean up their surroundings. They sweep particles into compact clusters, gradually reshaping and organizing their environment.
In a study recently published in Physical Review X, a team of researchers show that this remarkable sweeping behavior does not require a brain, or any kind of complex interaction between the worms and the particles. Instead, it emerges from the natural undulating motion and flexibility that the worms possess.
The study was co-led by Saad Bhamla, associate professor in Georgia Tech’s School of Chemical and Biomolecular Engineering, and Antoine Deblais of the University of Amsterdam.
Deblais said: “It is fascinating to see how living worms can organize their surroundings just by moving.” Bhamla added: “Their activity and flexibility alone are enough to collect particles and reshape their environment.”
By building simple robotic and computer models that mimic the living worms, the researchers discovered that only these two ingredients – activity and flexibility – are sufficient to reproduce the sweeping and collecting effects. The result is a self-organized, dynamic form of environmental restructuring driven purely by motion and shape.
Order emerges
The results do not just teach us a surprising lesson about worms. Understanding how these organisms spontaneously collect particles has much broader implications. On the technological side, what the researchers have learned could inspire the design of soft robots that clean or sort materials without needing sensors or pre-programmed intelligence.
Such robots, like the worms, would simply move and let order emerge from motion. “Brainless” machines of this sort could perhaps one day help remove microplastics or sediments from aquatic environments, or perform complex tasks in unpredictable terrains.
From a biological perspective, the results also offer insights into how elongated living organisms – not just worms, but also filamentous bacteria, or cytoskeletal filaments – can structure and modify their own habitats through simple physical interactions. Understanding this structuring and modifying behaviour has been a central question for, e.g., earthworms in their role in soil aeration.
From a biological perspective, the results also offer insights into how elongated living organisms – not just worms, but also filamentous bacteria, or cytoskeletal filaments – can structure and modify their own habitats through simple physical interactions. Understanding this structuring and modifying behaviour has been a central question for, e.g., earthworms in their role in soil aeration.
Team effort
This project grew out of curiosity about how living systems shape their environment without centralized control. Initial experiments with worms, conducted by Harry Tuazon (Bioengineering PhD 2024) at Georgia Tech, showed the unexpected particle collection patterns. This led the team to attempt to reproduce the behavior using robotic and simulated counterparts – something that worked surprisingly well. In the project, experimentalists and theorists worked side by side, allowing the team to uncover the physical principles behind this seemingly purposeful behavior.
Co-first author Rosa Sinaasappel conducted the robot experiments at the University of Amsterdam. “By mimicking the worms’ motion with simple brainless robots connected by flexible rubber links, we could pinpoint the two ingredients that are essential for the sweeping mechanism,” she said.
Co-first author Prathyusha Kokkoorakunnel Ramankutty, a research scientist in the Bhamla Lab at Georgia Tech, performed the computer simulations of the behavior. “Our computational model, built on simple ingredients like propulsion and flexibility, shows that this principle works across different scales and can be adapted for new designs, as demonstrated by a soft robotic sweeper that autonomously ‘cleans’ and reorganizes particles without programmed intelligence,” she explained.
The researchers will continue to investigate this type of behaviour in the future. While a mathematical model of active sweeping is now presented in a simple form, many challenging questions raised by this complex system remain open for theoreticians.
Multiple groups of students helped greatly with the robot experiments, doing projects in the lab. Their efforts ranged from performing the experiments to replacing the in total about 200 batteries, after perhaps one of the most difficult tasks: wrestling them free from the child-proof packaging.
CITATION:
Particle Sweeping and Collection by Active and Living Filaments, Sinaasappel, R., Prathyusha, K. R., Tuazon, Harry, Mirzahossein, E., Illien, P., Bhamla, Saad, and A. Deblais. Physical Review X (2026)
To ease this environmental burden, industry has worked to adopt renewable biopolymers in place of traditional plastics. However, developers of sustainable packaging have faced hurdles in blocking out moisture and oxygen, a barrier critical for protecting food, pharmaceuticals, and sensitive electronics.
Now, researchers at the Georgia Institute of Technology have developed a biologically based film made from natural ingredients found in plants, mushrooms, and food waste that can block moisture and oxygen as effectively as conventional plastics. Their findings were recently published in ACS Applied Polymer Materials.
“We’re using materials that are already abundant in and degrade in nature to produce packaging that won’t pollute the environment for hundreds or even thousands of years,” said Carson Meredith, a professor in Georgia Tech’s School of Chemical and Biomolecular Engineering (ChBE@GT) and executive director of the Renewable Bioproducts Institute. “Our films, composed of biodegradable components, rival or exceed the performance of conventional plastics in keeping food fresh and safe.”
Meredith’s research team has worked for more than a decade to develop environmentally friendly oxygen and water barriers for packaging. While earlier research using biopolymers showed promise, high humidity continued to weaken the barrier properties.
However, Meredith and his collaborators found a fix using a blend of these natural ingredients: cellulose (which gives plants their structure), chitosan (derived from crustacean-based food waste or mushrooms), and citric acid (from citrus fruits).
“By crosslinking these materials and adding a heat treatment, we created a thin film that reduced both moisture and oxygen transmission, even in hot, humid conditions simulating the tropics,” said lead author Yang Lu, a former postdoctoral researcher in ChBE@GT.
The barrier technology developed by the researchers consists of three primary components: a carbohydrate polymer for structure, a plasticizer to maintain flexibility, and a water-repelling additive to resist moisture. When cast into thin films, these ingredients self-organize at the molecular level to form a dense, ordered structure that resists swelling or softening under high humidity.
Even at 80 percent relative humidity, the films showed extremely low oxygen permeability and water vapor transmission, matching or outperforming common plastics such as poly(ethylene terephthalate) (PET) and poly(ethylene vinyl alcohol) (EVOH).
“Our approach creates barriers that are not only renewable, but also mechanically robust, offering a promising alternative to conventional plastics in packaging applications,” said Natalie Stingelin, professor and chair of Georgia Tech’s School of Materials Science and Engineering (MSE) and a professor in ChBE@GT.
The research team has filed for patent protection for the technology (patent pending). The research was supported by Mars Inc., Georgia Tech’s Renewable Bioproducts Institute, and the U.S. Department of Defense through the National Defense Science and Engineering Graduate Fellowship Program. Eric Klingenberg, a co-author of the study, is an employee of Mars, a manufacturer of packaged foods.
Citation: Yang Lu, Javaz T. Rolle, Tanner Hickman, Yue Ji, Eric Klingenberg, Natalie Stingelin, and Carson Meredith, “Transforming renewable carbohydrate-based polymers into oxygen and moisture-barriers at elevated humidity,” ACS Applied Polymer Materials, 2025.
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