Georgia Tech researchers were recently awarded $11.6 million from the NNSA to address this growing need — and to study and expand on existing models of transuranic chemistry, a branch of chemistry dedicated to studying elements with atomic numbers greater than that of uranium.

Led by School of Chemistry and Biochemistry Associate Professor Henry “Pete” La Pierre, the funding will serve to establish the Transuranic Chemistry Center of Excellence. Directed by La Pierre, the Center will house a collaborative network of five other universities and six national laboratories across the United States conducting both theoretical and applied research.

“Scientifically, actinides and transuranic elements present unique challenges to existing models of chemical bonding,” explains La Pierre. These elements are man-made radioactive metals, many of which are not available in large quantities. “There are amazing open-ended questions that are fundamental to our understanding of chemical bonding and activities, that serve to transform our knowledge of how the elements form bonds across the Periodic Table.”

Joining seven other universities, this funding comes to Georgia Tech as part of NNSA’s $100 million program establishing Stewardship Science Academic Alliances Centers of Excellence. A main goal of this program is to recruit, train, and educate the next generation of researchers in nuclear science and engineering.

“These cooperative agreements will allow NNSA to train the smartest and most skilled individuals while creating a direct pathway into our workforce with a diverse group of experts that can meet the evolving needs of the nuclear security enterprise,” said Kevin Greenaugh, Chief Science and Technology Officer for Defense Programs, in a recent press release.

“The science and engineering collaboration of this center is a true synergy,” says Martha Grover, professor and associate chair for Graduate Studies in the School of Chemical and Biomolecular Engineering and one of the collaborators for the Center. Anna Erickson, Woodruff Professor and associate chair for Research in the George W. Woodruff School of Mechanical Engineering, is another Georgia Tech collaborator. “This center provides a new example of the growing prominence of Georgia Tech in the nuclear field.”

Pushing the bounds of chemistry

“We are at core a synthetic inorganic chemistry group, which means we make new molecules and characterize them,” La Pierre explained. In his research as part of the Center, La Pierre will “be handling both radioactive and chemically reactive species to make new forms of matter.”

Characterizing new forms of matter is no easy task, requiring advanced techniques that allow scientists to envision and measure the properties of chemical bonds. Exposing the molecules to X-rays or neutrons and measuring how they scatter or diffract (depending on the experimental design), gives researchers insights into the chemical bonds that are formed.

Using a combination of these advanced techniques as well as theoretical models, La Pierre and the collaborators of the Center will be creating new molecules out of actinides and lanthanides — metallic elements on the bottom of the periodic table — and studying the details of their structures and behavior during chemical reactions. As these elements are not found naturally, the structures and properties of many of these compounds have never been studied before.

“We are creating systems that challenge existing bonding models, which we then have to go back and build new theoretical techniques in order to understand what we're seeing,” La Pierre explained. “So, this does push the forefront of our understanding of basic chemical model systems.”

To push those boundaries, scientists and engineers will be working together across the country — led by Georgia Tech. 

“There are so many faculty at Georgia Tech working in nuclear science and technology,” says Grover. “This center gives me the opportunity to collaborate with Prof. La Pierre and Erickson for the first time, in the area of flow chemistry and separations.”

“I'm looking forward to working with some incredibly talented colleagues whom I don't normally get a chance to work with,” says La Pierre. “And now we have the opportunity to work together every week with fantastic students that I would never have met otherwise. That's the main draw for me.”

Researchers at Emory University and Georgia Tech demonstrated this connection in two new papers published by Nature Chemistry: “Design of multi-phase dynamic chemical networks” and “Catalytic diversity in self-propagating peptide assemblies.”

“In the first paper we showed that you can create tension between a chemical and physical system to give rise to more complex systems. And in the second paper, we showed that these complex systems can have remarkable and unexpected functions,” said David Lynn, a systems chemist at Emory who led the research. “The work was inspired by our current understanding of Darwinian selection of protein misfolding in neurodegenerative diseases.”

The Lynn lab is exploring ways to potentially control and direct the processes of these proteins – known as prions – adding to knowledge that might one day help to prevent disease, as well as open new realms of synthetic biology. For the current papers, Emory collaborated with the research group of Martha Grover, a professor in the Georgia Tech School of Chemical & Biomolecular Engineering, to develop molecular models for the processes.

Darwin’s theory of evolution by natural selection is well-established – organisms adapt over time in response to environmental changes. But theories about how life emerges – the movement through a pre-Darwinian world to the Darwinian threshold – remain murkier.

The researchers started with single peptides and engineered in the capacity to spontaneously form small proteins, or short polymers. “These protein polymers can fold into a seemingly endless array of forms, and sometimes behave like origami,” Lynn explained. “They can stack into assemblies that carry new functions, like prions that move from cell-to-cell, causing disease.” 

This protein misfolding provided the model for how physical changes could carry information with function, a critical component for evolution. To try to kickstart that evolution, the researchers engineered a chemical system of peptides and coupled it to the physical system of protein misfolding. The combination results in a system that generates step-by-step, progressive changes, through self-driven environmental changes.

“The folding events, or phase changes, drive the chemistry and the chemistry drives the replication of the protein molecules,” Lynn said. “The simple system we designed requires only the initial intervention from us to achieve progressive growth in molecular order. The challenge now becomes the discovery of positive feedback mechanisms that allow the system to continue to grow.”

The researchers used mathematical modeling to help guide the experimental work.

“Modeling requires us to formulate our hypotheses in the language of mathematics, and then we use the models to design further experiments to test the hypotheses,” said Grover. “In this project, the hypotheses were sometimes invalidated by these further experiments, but ultimately this led us to a better understanding of the underlying chemical and physical events and their interactions."

The research was funded by the McDonnell Foundation, the National Science Foundation’s Materials Science Directorate, Emory University’s Alzheimer’s Disease Research Center, the National Science Foundation’s Center for Chemical Evolution and the Office of Basic Energy Sciences of the U.S. Department of Energy.

Additional co-authors of the papers include: Toluople Omosun, Seth Childers, Dibyendu Das and Anil Mehta (Emory Departments of Chemistry and Biology); Ming-Chien Hsieh (Georgia Tech School of Chemical & Biomolecular Engineering); and Neil Anthony and Keith Berland (Emory Department of Physics).

- Written by Carol Clark, Emory University

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That last ingredient may have helped gene-like strands to copy themselves in puddles for the first time ever, billions of years ago when Earth was devoid of life, researchers at the Georgia Institute of Technology have found. Their novel discoveries add to a growing body of evidence that suggests first life may have evolved with relative ease, here and possibly elsewhere in the universe.

And they offer a straightforward answer to a gnawing 50-year-old question: How did precursors to the present-day genetic code first duplicate themselves before the existence of enzymes that are indispensable to that process today? 

The spice of life?

For generations, scientists pursuing an answer performed experiments in water but hit a wall.

Georgia Tech researchers Christine He and Isaac Gállego overcame it by adding an off-the-shelf viscous solvent (the thickener). In separate experiments with DNA then RNA, the copying process proceeded.

“I think it’s very, very different from anything that’s been done before,” said researcher He. “We can change the physical environment in an easy way, and promote these processes that wouldn’t happen in conditions ordinarily being used.”

Easy recipe

Easy is crucial, said Martha Grover, a professor who oversaw the research at Georgia Tech’s School of Chemical and Biomolecular Engineering. Easy reactions are likely to be more productive and more prevalent.

“A simple and robust process like this one could have operated in a variety of environments and concentrations making it more realistic in moving evolution forward,” she said.

Grover’s lab and that of Nick Hud at Georgia Tech’s School of Chemistry and Biochemistry published the results on Monday, October 10, 2016 in the journal Nature Chemistry. Their research has been funded by the National Science Foundation and the NASA Astrobiology Program under the NASA/NSF Center for Chemical Evolution.

Nucleotide noodles

Earliest life was based on RNA, or a similar polymer, according to a hypothesis called the RNA World. In that scenario, on the evolutionary timeline, the self-replication of RNA strands long enough to be potential genes would roughly mark the doorstep to life.

Those long nucleotide chains may have been mixed together in puddles with shorter nucleotide chains. Heat from the sun would have made long strands detach from their helix structures, giving short ones a chance to match up with them, and become their copies. 

But there’s a problem.

In water alone, when cooling sets in, the long chains snap back into their helix structure so rapidly that there’s no time for the matching process with the shorter chains. That snapping shut, which happens in both RNA and DNA, is called “strand inhibition,” and in living cells, enzymes solve the problem of keeping the long chains apart while gene strands duplicate.

More like a stew 

“The problem is a problem in water, which everybody sort of looks at in prebiotic (pre-life) chemistry,” said graduate research assistant He. She felt it was time to rethink that, and her expertise in chemical engineering helped.

High viscosity has been known to slow down the movement of long strands of DNA, RNA and other polymers. 

“It’s a little like making them swim in honey,” Grover said. Applying that to origin-of-life chemistry seemed obvious, because in prebiotic times, there probably were quite a few sticky puddles.

“In that solution, it gives the short nucleotides, which move faster, time to jump onto the long strand and piece together a duplicate of the long strand,” researcher He said. In her experiments, it worked.

Hairpins in the soup

And it produced an encouraging surprise. The DNA and RNA strands folded onto themselves forming shapes called hairpins. 

“In the beginning, we didn’t realize the importance of the internal structure,” Christine He said. Then they noticed that the shape was helping keep RNA and DNA available for the pairing process. “Hairpin formation is integral to keeping them open,” Grover said.

But it also could have accelerated chemical evolution in another way.  “The solution is selecting here for sequences that fold, and that would have more potential for functional activity – like a ribozyme,” said researcher He.

Ribozymes are enzymes made of RNA, and enzymes catalyze biochemical processes. To have them evolve in the same solution that promotes genetic code replication could have shortened the path to first life.

“You really need to amplify functional sequences for evolution to move forward,” Grover said. The folds were an unexpected side-effect, and finding them paves the way for future research.

Next ingredient?

The Georgia Tech scientists used real gene strands in their experiments, which may sound mundane, but in the past, some researchers have specially engineered DNA and RNA sequences in attempts to arrive at similar results.

He and Gállego’s use of a naturally occurring gene, rather than a specifically engineered sequence, shows that viscosity could have been a very general solution to promote copying of nucleic acids with mixed length and sequences.

To facilitate quick, clear outcomes, the Georgia Tech researchers used purified short nucleotide chains and applied them in ratios that favored productive reactions. But they had started out with messier, less pure ingredients, and the experience was worthwhile.

“Considering a pre-biotic soup, it’s probably messy; it’s got a lot of impurities,” Christine He said. “When we first started out with more impure nucleotides, it still worked. Maybe the same reaction really could have happened in a messy puddle billions of years ago.”

The viscous solvent was glycholine, a mixture of glycerol and choline chloride. It was not likely present on pre-biotic Earth, but other viscous solvents likely were.

Also, after the short strands matched up to each long one, the researchers did apply an enzyme to join the aligned short pieces into a long chain, in a biochemical process called ligation.

The enzymes would not have been present on a prebiotic Earth, and although there are chemical procedure for ligating RNA, “no one has developed a chemistry so robust yet that it could replace the enzyme,” Grover said. 

Finding one that could have worked on a prebiotic Earth would be a worthy aim for further research.

READ: More about chemical engineering, viscosity and DNA

READ: Possible precusor of RNA forms spontaneously in water

Brandon Laughlin from Georgia Tech coauthored the paper. The research was funded by the National Science Foundation and the NASA Astrobiology Program under the NASA/NSF Center for Chemical Evolution (grant number CHE-1504217) and by the NSF Graduate Research Fellowship (grant number DGE-1148903). Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsoring agencies.

Research reported July 15 in the journal Angewandte Chemie International Edition demonstrates that important molecules of contemporary life, known as polypeptides, can be formed simply by mixing amino and hydroxy acids – which are believed to have existed together on the early Earth – then subjecting them to cycles of wet and dry conditions.

This simple process, which could have taken place in a puddle drying out in the sun and then reforming with the next rain, works because chemical bonds formed by one compound make bonds easier to form with the other.

The study, titled “Ester-Mediated Amide Bond Formation Driven by Wet-Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth,” supports the theory that life could have begun on dry land, perhaps even in the desert, where cycles of nighttime cooling and dew formation are followed by daytime heating and evaporation.

Just 20 of these day-night, wet-dry cycles were needed to form a complex mixture of polypeptides in the lab. The process also allowed the breakdown and reassembly of the organic materials to form random sequences that could have led to the formation of the polypeptide chains that were needed for life.

“The simplicity of using hydration-dehydration cycles to drive the kind of chemistry you need for life is really appealing,” said lead author Nicholas Hud, a professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology, and director of the NSF/NASA Center for Chemical Evolution, which is supported by the NSF Centers for Chemical Innovation Program and the NASA Astrobiology Program. “It looks like dry land would have provided a very favorable environment for getting the chemistry necessary for life started.”

Sheng-Sheng Yu, a graduate student in Georgia Tech's School of Chemical and Biomolecular Engineering (ChBE), was co-first author of the study. Other co-authors include Yu's advisor, ChBE Professor Martha Grover; Georgia Tech Postdoctoral Fellow Jay Forsythe; Ramanarayanan Krishnamurthy, an associate professor of chemistry at the Scripps Research Instituteas; Irena Mamajanov, a Simons Foundation Fellow at the Carnegie Institution for Science; and Professor Facundo M. Fernández of Georgia Tech's School of Chemistry and Biochemistry.

Origin-of-life scientists had previously made polypeptides from amino acids by heating them well past the boiling point of water, or by driving polymerization with activating chemicals. But the high temperatures are beyond the point at which most life could survive, and the robust availability of activating chemicals on the early Earth is questionable. The simplicity of the wet-dry cycle therefore makes it attractive to explain how peptides could have formed, Hud added.

The idea for combining chemically similar amino acids and hydroxyl acids was inspired by the demonstration that polyesters are easy to form by repetitive hydration-dehydration cycles and the fact that esters are activated to attack by the amino group of amino acids. The potential importance of this reaction in the earliest stages of life is supported by studies of meteorites, which revealed that both compounds would have been present on the prebiotic Earth.

Hydroxy acids combine to form polyester, better known as a synthetic textile fiber, and that reaction requires less energy than formation of the amide bonds needed to create peptides from amino acids. In the wet-dry cycles, formation of polyester comes first – which then facilitates the more difficult peptide formation, Hud said.

“The ester linkages that we are making in the polyester can serve as an activating agent formed within the solution,” he explained. “Over the course of a very simple chemical evolution, the polymers progress from having hydroxy acids with ester linkages to amino acids with peptide linkages. The hydroxy acids are gradually replaced through the wet and dry cycles because the ester bonds holding them together are not as stable as the peptide bonds.”

Experimentally, graduate student Sheng-Sheng Yu put the amino and hydroxy acid mixtures through 20 wet-dry cycles to produce molecules that are a mixture of polyesters and peptides, containing as many as 14 units. After just three cycles, and at temperatures as low as 65 degrees Celsius, peptides consisting of two and three units began to form. Postdoctoral fellow Jay Forsythe confirmed the chemical structures using NMR mass spectrometry.

“We allowed the peptide bonds to form because the ester bonds lowered the energy barrier that needed to be crossed,” Hud added.

On the early Earth, those cycles could have taken 20 days and nights – or perhaps much longer if the heating and drying cycles corresponded to seasons of the year.

Beyond easily forming the polypeptides, the wet-dry process has an additional advantage. It allows compounds like peptides to be regularly broken apart and reformed, creating new structures with randomly-ordered amino acids. This ability to recycle the amino acids not only conserves organic material that may have been in short supply on the early Earth, but also provides the potential for creating more useful combinations.

A combination of hydroxy and amino acids likely existed in the prebiotic soup of the early Earth, but analyzing such a “messy” reaction was challenging, Hud said. “We were led into this idea that a mixture might work better than separate components,” he explained. “It might have been messy at the start, but it’s easier to get going than a pristine chemical reaction.”

Beyond helping explain how life might have started, the wet-dry cycles could also provide a new way to synthesize polypeptides. Existing techniques produce the chemicals through genetic engineering of microorganisms, or through synthetic organic chemistry. The wet-dry cycling could provide a simpler and more sustainable water-based process for producing these chemicals.

The demonstration of peptide formation opens the door to asking other questions about how life may have gotten going in prebiotic times, said research team member Krishnamurthy. Future studies will include a look at the sequences formed, whether there are sequences favored by the process, and what sequences might result. The process could ultimately lead to reactions able to continue without the wet-dry cycles.

“If this process were repeated many times, you could grow up a peptide that could acquire a catalytic property because it had reached a certain size and could fold in a certain way,” Krishnamurthy said. “The system could begin to develop certain emergent characteristics and properties that might allow it to self-propagate.”

In addition to those already named, the paper’s authors include Irena Mamajanov, Martha A Grover, and Facundo M. Fernández, all from Georgia Tech.

This research was supported by the NSF Centers for Chemical Innovation Program and the NASA Astrobiology Program under the NSF/NASA Center for Chemical Evolution under grant number CHE-1004570. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NSF or NASA.

- Article written by John Toon of Georgia Tech Research Horizons

The award, which is bestowed upon only onerecipient each year, recognizes an individual under the age of 40 foroutstanding contributions to chemical engineering computing and systemstechnology literature. In a congratulatory letter, Dr. Mayuresh V. Kothare,chair of the AIChE CAST Division Awards committee, lauded Dr. Grover for developingmethods for engineering materials structures that are both systematic andpractical.

A member of the Center for Chemical Evolutionand the Center for Organic Photonics and Electronics (COPE) at Georgia Tech, Dr.Grover conducts research that focuses on understanding macromolecularorganization and the emergence of biological function through the kinetics ofself-assembly, stochastic modeling, model reduction, machine learning,experimental design, robust parameter design, and estimation.

A 2004 recipient of a National ScienceFoundation (NSF) Faculty Early Career Development (CAREER) Program Award, Dr.Grover joined the ChBE faculty in 2003 after receiving her doctorate degreefrom the California Institute of Technology.

Dr. Grover will formally receive theOutstanding Young Researcher Award at the CAST Division dinner, which will beheld at the AIChE Annual Meeting this fall in Minneapolis. Sponsored by AirProducts and Chemicals, Inc., the award includes a plaque and $3,000.