School of Biological Sciences

Natural products – small organic molecules made by living things like bacteria, fungi, and plants – are at the forefront of medical innovation. The majority of clinically used antibiotics and drugs are derived from these unique molecules, and innovations in their development, identification, and synthesis are driving the fight against antibiotic-resistant pathogens.

In the race to develop new pharmaceuticals, an increasing number of biochemists are looking to discover new natural products – and uncover the mechanisms that produce and influence them. And Georgia Tech School of Chemistry and Biochemistry Assistant Professor Vinayak Agarwal is helping lead that charge. “I’m interested in how and why natural products are created in nature, what we can learn from their processes, and how we can harness nature's capabilities for interesting applications,” Agarwal says.

Now a $700,000 NSF CAREER grant will help him do so. The National Science Foundation Faculty Early Career Development Award is a five-year funding mechanism designed to help promising researchers establish a personal foundation for a lifetime of leadership in their field. Known as CAREER awards, the grants are NSF’s most prestigious funding for untenured assistant professors.

Agarwal’s award specifically focuses on his research into peptides, short strings of amino acids that make up proteins. “We’re making new types of peptides and modified peptides,” Agarwal explains. “Modifications in a lot of antibiotics that we use are actually peptides.” Over 100 peptide-based drugs are currently available in the US, where they’re used to treat conditions ranging from type-2 diabetes to MS.

Changing the tides with peptides

While peptides are naturally made in the body, they can also be synthesized in the lab, where they’re modified using different enzymes. By harnessing these enzymes, peptides can be better tailored to suit needs – they can be changed to interact with biologies in different ways, an essential aspect of creating new medicines.

Discovering and studying the enzymes that modify peptides is a key part of Agarwal’s research, as is understanding the mechanisms that these enzymes use to recognize and bind to the peptides. This is called “enzymatic modification,” and it’s a lush playing field for discovering new chemical reactions. “We want to solve the need of the chemistry community when it comes to peptide modifications, providing new reactions to the community regarding peptide development and peptide modification,” Agarwal says.

While gene mining has revealed some enzymes that might be useful in modifying peptides, the reactions caused by these enzymes and the resulting structure of the peptide are not fully understood: in-situ research is needed. Agarwal’s first goal is to discover new chemical reactions between peptides and enzymes by leveraging in vivo synthetic biology (inside living organisms) and in vitro biochemistry experiments (outside of living organisms).

Agarwal also hopes to better understand how peptides and proteins interact, and why so many chemical reactions depend on them. “Peptide-protein interactions and modification of peptides is a central tenet of all biological processes,” Agarwal explains. “We want to know how and why peptides are chosen by nature as scaffolding for chemical reactions.”

Hands-on research and the student connection

Leveraging in vivo synthetic biology and in vitro biochemistry experiments means a lot of hands-on research. “The team is making peptides in the lab using an E. coli bacteria,” Agarwal explains. “We provide genes to an E. coli bacteria, and it modifies the chemistries using specific enzymes.”

What does this research look like? Petri dishes. A lot of petri dishes. And a lot of opportunities for students. “One of our key goals is to use our interdisciplinary training to engage underserved students in research and lab experience. We want to educate, train, and diversify the next generation of scientists,” Agarwal says. “We are designing new courses in the laboratory which introduces undergraduates to new coursework and experiments in peptide science.”

Some of these opportunities are already bearing fruit: Agarwal recently collaborated with a team of undergraduates over a semester-long lab course, which included conducting laboratory research and publishing their findings.

Now, Agarwal plans to use this new CAREER grant to further expand opportunities for undergraduates, and will develop original curriculum starting with peptide-based lab research together with scientific communication and writing.

“The training that students are going to get provides a broad experience in biological and chemical science,” Agarwal says. “We want our students to learn mechanisms for peptide modifications, but the training is broadly applicable. It will prepare them to move forward in STEM – and especially graduate studies – but will also prepare them for industry careers, government and regulatory science, graduate studies, and more. This kind of background is applicable in all fields.”

All in all, Agarwal expects the research to span across this decade and into the next. There’s excitement in that timeline, too – ten-plus years of teaching, discovery, and opportunities for students, at Georgia Tech and beyond.

“For me, the biggest thing is student progress, as well as curriculum development and training,” Agarwal says. “That’s my driving force.”

Five Georgia Tech College of Sciences researchers have been awarded CAREER grants from the National Science Foundation (NSF).

These Faculty Early Career Development Awards are part of a five-year funding mechanism designed to help promising researchers establish a personal foundation for a lifetime of leadership in their field. The grants are NSF’s most prestigious funding for untenured assistant professors.

Read more:
Making Medicines: Vinayak Agarwal’s research into peptides, and their medicinal potential
The Fundamental Questions: Jesse McDaniel’s new framework for predicting chemical reaction rates, leveraging computer modeling
Chasing Chaos: Alex Blumenthal’s research in chaos, fluid dynamics
Solving Infinite Problems: Anton Bernshteyn’s new, unified theory of descriptive combinatorics and distributed algorithms
Gauging Glaciers: Alex Robel's new ice sheet modeling tool

One of the most exciting parts of the CAREER grants is that they support new faculty, who are often working at the frontier of their fields. “I am excited about the CAREER research because we are really focusing on fundamental questions that are central to all of chemistry,” says Jesse McDaniel (School of Chemistry and Biochemistry) about his project, which focuses on creating a new framework to predict the rates of chemical reactions, leveraging computer science.

Anton Bernshteyn’s (School of Mathematics) work in the recently emerged field of descriptive combinatorics is also on the cutting edge of discovery. “There’s this new communication between separate fields of math and computer science— this huge synergy right now— it’s incredibly exciting,” Bernshteyn explains. “Right now we’re only starting to glimpse what’s possible.”

Each award also includes a teaching and outreach component: Vinayak Agarwal (School of Chemistry and Biochemistry) plans to use his grant to not only investigate peptides, but also to train the next generation of leaders, emphasizing student inclusion from diverse backgrounds: “The training is broadly applicable,” says Agarwal. “It will prepare students to move forward in STEM – and especially graduate studies – but will also prepare them for industry careers, government and regulatory science, graduate studies, and more. This kind of background is applicable in all fields.”

Alex Blumenthal (School of Mathematics), who is investigating the intersection of chaos, turbulence– including fluid dynamics– mathematics, and computer-assisted proof, agrees. “There’s a whole lot of new stuff to do,” Blumenthal says. “There’s a growing community of people studying random dynamics, and a growing community of people doing computer proofs– it’s a great place for undergrads to have meaningful research experiences.”

Alex Robel (School of Earth and Atmospheric Sciences), emphasizes the broad impacts of the CAREER grant projects. Robel is working to create a new ice sheet modeling tool, which will be accessible to anyone, and just require the use of a computer browser. “Ultimately,” Robel says, “this project will empower more people in the community to use these models and to use these models together with the observations that they're taking.”

Natural products – small organic molecules made by living things like bacteria, fungi, and plants – are at the forefront of medical innovation. The majority of clinically used antibiotics and drugs are derived from these unique molecules, and innovations in their development, identification, and synthesis are driving the fight against antibiotic-resistant pathogens.

In the race to develop new pharmaceuticals, an increasing number of biochemists are looking to discover new natural products – and uncover the mechanisms that produce and influence them. And Georgia Tech School of Chemistry and Biochemistry Assistant Professor Vinayak Agarwal is helping lead that charge. “I’m interested in how and why natural products are created in nature, what we can learn from their processes, and how we can harness nature's capabilities for interesting applications,” Agarwal says.

Now a $700,000 NSF CAREER grant will help him do so. The National Science Foundation Faculty Early Career Development Award is a five-year funding mechanism designed to help promising researchers establish a personal foundation for a lifetime of leadership in their field. Known as CAREER awards, the grants are NSF’s most prestigious funding for untenured assistant professors.

Agarwal’s award specifically focuses on his research into peptides, short strings of amino acids that make up proteins. “We’re making new types of peptides and modified peptides,” Agarwal explains. “Modifications in a lot of antibiotics that we use are actually peptides.” Over 100 peptide-based drugs are currently available in the US, where they’re used to treat conditions ranging from type-2 diabetes to MS.

Changing the tides with peptides

While peptides are naturally made in the body, they can also be synthesized in the lab, where they’re modified using different enzymes. By harnessing these enzymes, peptides can be better tailored to suit needs – they can be changed to interact with biologies in different ways, an essential aspect of creating new medicines.

Discovering and studying the enzymes that modify peptides is a key part of Agarwal’s research, as is understanding the mechanisms that these enzymes use to recognize and bind to the peptides. This is called “enzymatic modification,” and it’s a lush playing field for discovering new chemical reactions. “We want to solve the need of the chemistry community when it comes to peptide modifications, providing new reactions to the community regarding peptide development and peptide modification,” Agarwal says.

While gene mining has revealed some enzymes that might be useful in modifying peptides, the reactions caused by these enzymes and the resulting structure of the peptide are not fully understood: in-situ research is needed. Agarwal’s first goal is to discover new chemical reactions between peptides and enzymes by leveraging in vivo synthetic biology (inside living organisms) and in vitro biochemistry experiments (outside of living organisms).

Agarwal also hopes to better understand how peptides and proteins interact, and why so many chemical reactions depend on them. “Peptide-protein interactions and modification of peptides is a central tenet of all biological processes,” Agarwal explains. “We want to know how and why peptides are chosen by nature as scaffolding for chemical reactions.”

Hands-on research and the student connection

Leveraging in vivo synthetic biology and in vitro biochemistry experiments means a lot of hands-on research. “The team is making peptides in the lab using an E. coli bacteria,” Agarwal explains. “We provide genes to an E. coli bacteria, and it modifies the chemistries using specific enzymes.”

What does this research look like? Petri dishes. A lot of petri dishes. And a lot of opportunities for students. “One of our key goals is to use our interdisciplinary training to engage underserved students in research and lab experience. We want to educate, train, and diversify the next generation of scientists,” Agarwal says. “We are designing new courses in the laboratory which introduces undergraduates to new coursework and experiments in peptide science.”

Some of these opportunities are already bearing fruit: Agarwal recently collaborated with a team of undergraduates over a semester-long lab course, which included conducting laboratory research and publishing their findings.

Now, Agarwal plans to use this new CAREER grant to further expand opportunities for undergraduates, and will develop original curriculum starting with peptide-based lab research together with scientific communication and writing.

“The training that students are going to get provides a broad experience in biological and chemical science,” Agarwal says. “We want our students to learn mechanisms for peptide modifications, but the training is broadly applicable. It will prepare them to move forward in STEM – and especially graduate studies – but will also prepare them for industry careers, government and regulatory science, graduate studies, and more. This kind of background is applicable in all fields.”

All in all, Agarwal expects the research to span across this decade and into the next. There’s excitement in that timeline, too – ten-plus years of teaching, discovery, and opportunities for students, at Georgia Tech and beyond.

“For me, the biggest thing is student progress, as well as curriculum development and training,” Agarwal says. “That’s my driving force.”

Five Georgia Tech College of Sciences researchers have been awarded CAREER grants from the National Science Foundation (NSF).

These Faculty Early Career Development Awards are part of a five-year funding mechanism designed to help promising researchers establish a personal foundation for a lifetime of leadership in their field. The grants are NSF’s most prestigious funding for untenured assistant professors.

Read more:
Making Medicines: Vinayak Agarwal’s research into peptides, and their medicinal potential
The Fundamental Questions: Jesse McDaniel’s new framework for predicting chemical reaction rates, leveraging computer modeling
Chasing Chaos: Alex Blumenthal’s research in chaos, fluid dynamics
Solving Infinite Problems: Anton Bernshteyn’s new, unified theory of descriptive combinatorics and distributed algorithms
Gauging Glaciers: Alex Robel's new ice sheet modeling tool

One of the most exciting parts of the CAREER grants is that they support new faculty, who are often working at the frontier of their fields. “I am excited about the CAREER research because we are really focusing on fundamental questions that are central to all of chemistry,” says Jesse McDaniel (School of Chemistry and Biochemistry) about his project, which focuses on creating a new framework to predict the rates of chemical reactions, leveraging computer science.

Anton Bernshteyn’s (School of Mathematics) work in the recently emerged field of descriptive combinatorics is also on the cutting edge of discovery. “There’s this new communication between separate fields of math and computer science— this huge synergy right now— it’s incredibly exciting,” Bernshteyn explains. “Right now we’re only starting to glimpse what’s possible.”

Each award also includes a teaching and outreach component: Vinayak Agarwal (School of Chemistry and Biochemistry) plans to use his grant to not only investigate peptides, but also to train the next generation of leaders, emphasizing student inclusion from diverse backgrounds: “The training is broadly applicable,” says Agarwal. “It will prepare students to move forward in STEM – and especially graduate studies – but will also prepare them for industry careers, government and regulatory science, graduate studies, and more. This kind of background is applicable in all fields.”

Alex Blumenthal (School of Mathematics), who is investigating the intersection of chaos, turbulence– including fluid dynamics– mathematics, and computer-assisted proof, agrees. “There’s a whole lot of new stuff to do,” Blumenthal says. “There’s a growing community of people studying random dynamics, and a growing community of people doing computer proofs– it’s a great place for undergrads to have meaningful research experiences.”

Alex Robel (School of Earth and Atmospheric Sciences), emphasizes the broad impacts of the CAREER grant projects. Robel is working to create a new ice sheet modeling tool, which will be accessible to anyone, and just require the use of a computer browser. “Ultimately,” Robel says, “this project will empower more people in the community to use these models and to use these models together with the observations that they're taking.”

The Krish Roy - GRA Travel Award is a new travel award endowed by Professor Krishnendu Roy with funding provided by the Georgia Research Alliance (GRA). Roy is a Regents’ Professor and the Robert A. Milton Endowed Chair in Biomedical Engineering. He also serves as Director of the NSF Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), the Marcus Center for Cell Therapy Characterization and Manufacturing (MC3M), and the Center for ImmunoEngineering. The award was designed to support to IBB-affiliated undergraduate, graduate, and postdoctoral trainees conducting research in cell manufacturing, drug delivery, immunoengineering, and regenerative medicine.

Ten finalists (pictured left) were selected to receive a stipend to travel to a domestic or international conference or workshop to present their research work.

“The Krish Roy Travel award allowed me to participate in my first conference of my graduate school career." said Parisa Keshavarz-Joud. "I had the opportunity to present a poster on my research at the Physical Virology Gordon Research Conference in January 2023 and interact with experts in the field. This experience broadened my knowledge of the field and helped me in developing new ideas about the next steps of my project.”

Elijah Holland used his award in January to attend the Fibronectin Gordon Research Conference in Ventura, California. In expressing gratitude for the award, Holland shared that he was able to meet leaders in the cell adhesion field and gave his first oral research presentation, titled "Mechanotransduction at Focal Adhesions: Interplay among Force, FAs, and YAP."

Fourth-year ChemE PhD student Hyun Jee Lee plans to use the award to her support her first experience at an international seminar and conference, where she will present her research and connect with other researchers around the world. Lee's research focus is developing microfluidic tools to study cellular and molecular mechanisms in small organisms. "I'm particularly interested in investigating brain activity changes associated with learning in C. elegans." Lee explained. "I'm very grateful to have received the award."

Awardees (pictured from top left to right):

John Cox, Graduate Research Assistant, Chemical and Biomolecular Engineering

Yarelis Gonzalez-Vargas, Graduate Student, Biomedical Engineering

Travis Rotterman, Ph.D., Postdoctoral Fellow, Biological Sciences

Wenting Shi, Graduate Research Assistant, Chemistry and Biochemistry

Kamisha Hill, Graduate Research Assistant, Chemistry and Biochemistry

Paris Keshavarz-Joud, Graduate Research Assistant, Chemistry and Biochemistry

Elijah Holland, Graduate Research Assistant, Mechanical Engineering

Hun Jee Lee, Graduate Student, Chemical Engineering

Maeve Janecka, Undergraduate Student, Chemical and Biomolecular Engineering

Sunny (Chao-yi) Lu, Graduate Research Assistant, Chemical and Biomolecular Engineering

Fermented foods like kimchi have been an integral part of Korean cuisine for thousands of years. Since ancient times, Korean chefs have used onggi — traditional handmade clay jars — to ferment kimchi. Today, most kimchi is made through mass fermentation in glass, steel, or plastic containers, but it has long been claimed that the highest quality kimchi is fermented in onggi.

Kimchi purists now have scientific validation, thanks to recent research from David Hu, professor in the George W. Woodruff School of Mechanical Engineering and the School of Biological Sciences at Georgia Tech, and Soohwan Kim, a second-year Ph.D. student in Hu’s lab.

In a combined experimental and theoretical study, Hu and Kim measured carbon dioxide levels in onggi during kimchi fermentation and developed a mathematical model to show how the gas was generated and moved through the onggi’s porous walls. By bringing the study of fluid mechanics to bear on an ancient technology, their research highlights the work of artisans and provides the missing link for how the traditional earthenware allows for high quality kimchi.

Their research was published in the Journal of the Royal Society Interface.

“We wanted to find the ‘secret sauce’ for how onggi make kimchi taste so good,” Hu said. “So, we measured how the gases evolved while kimchi fermented inside the onggi — something no one had done before.”

The porous structure of these earthenware vessels mimics the loose soil where lactic acid bacteria — known for their healthy probiotic nature — are found. While previous studies have shown that kimchi fermented in onggi has more lactic acid bacteria, no one knew exactly how the phenomenon is connected to the unique material properties of the container.

First, Kim obtained a traditional, handmade onggi jar from an artisan in his hometown in Jeju, South Korea, a region famous for onggi. Back at Georgia Tech, Hu and Kim first tested the permeability of the onggi by observing how water evaporated through the container over time.

Next, they installed carbon dioxide and pressure sensors into both the onggi and a typical, hermetically sealed glass jar. They prepared their own salted cabbage and placed it in both containers. They then used the sensors to measure and compare the change in carbon dioxide — a signature of fermentation.

Hu and Kim also developed a mathematical model based on the porosity of the onggi. The model allowed them to infer the generation rate of carbon dioxide, since the onggi lets carbon dioxide out gradually.

They concluded that the onggi’s porous walls permitted the carbon dioxide to escape the container, which accelerated the speed of fermentation. The onggi’s porosity also functioned as a “safety valve,” resulting in a slower increase in carbon dioxide levels than the glass jar while blocking the entry of external particles. Their data revealed that the carbon dioxide level in onggi was less than half of that in glass containers.

They also found that the beneficial bacteria in the onggi-made kimchi proliferated 26% more than in the glass counterpart. In the glass jar, the lactic acid bacteria became suffocated by their own carbon dioxide in the closed glass container. It turns out that, because the onggi releases carbon dioxide in small rates, the lactic acid bacteria are happier and reproduce more.

“Onggi were designed without modern knowledge of chemistry, microbiology, or fluid mechanics, but they work remarkably well,” Kim said. “It’s very interesting to get these new insights into ancient technology through the lens of fluid dynamics.”

Onggi’s semiporous nature is unique compared to other forms of earthenware. A clay container that leaks, but only slightly, is not easy to make. Terra cotta containers, for example, quickly leak water.

“It's amazing that, for thousands of years, people have been building these special containers out of dirt, but in many ways, they are very high tech,” Hu said. “We discovered that the right amount of porosity enables kimchi to ferment faster, and these onggi provide that.”

Kim said that some artisans still use ancient methods when making onggi, but their numbers are decreasing. Now, the market is flooded with inauthentic versions of the vessels.

“We hope this study draws attention to this traditional artisan work and inspires energy-efficient methods for fermenting and storing foods,” he said. “Also, the onggi are quite beautiful.”

Citation: Kim Soohwan and Hu David L. Onggi’s permeability to carbon dioxide accelerates kimchi fermentation. J. R. Soc. Interface. 2023.

DOI: https://doi.org/10.1098/rsif.2023.0034

This material was supported by the Woodruff Faculty fellowship and the NSF Physics of Living Systems student network.