Chronic itch is defined as itch persisting for more than six weeks. Because chronic itch is associated with most skin diseases, it is the most common reason for visiting a dermatologist. In addition to being uncomfortable, repeated scratching may result in infection and scarring, making chronic itch socially and occupationally debilitating.

Until recently researchers have experienced difficulty in visualizing the itch-sensing neurons that innervate the skin and are responsible for sensing itch sensation. However, a team of Georgia Tech researchers from the School of Biological Science has combined different cutting-edge techniques to solve this problem.

“We created a new transgenic mouse line that allowed us to, for the first time, see individual itch neurons in the skin,” says Yanyan Xing, a postdoctoral fellow in the Han laboratory. “This is very exciting!” she continued, “Because there are so many neurons in the skin, they often overlap on top of one another. This makes it impossible to determine the size, frequency, or distribution of the neurons.”

Such a state makes it impossible for researchers to perform any sort of detailed analysis on the neurons. For instance, the researchers cannot tell the number of axons per neuron, look for patterns in the spatial density of neurons, or see if the neurons are attached to any specific structures.  “In contrast,” Xing explained, “our transgenic mouse line allows us to perform ‘sparse-labeling’ so that only a few neurons, less than 1%, are visible. Now, we can visualize individual neurons!”

Xing completed this work with a graduate student, Haley Steele, and four other fellow School of Biological Sciences researchers under the direction of Dr. Liang Han. The team published their results, “Visualizing the Itch-Sensing Skin Arbors,” in The Journal of Investigative Dermatology. Specifically, the team looked at a group of itch sensing neurons that are identified by the presence of a single protein, MrgprC11. They, therefore, call this group of neurons MrgprC11+ itch-sensing neurons.

To visualize these MrgprC11+ neurons, the team used a histological staining technique known as PLAP. This technique turns the individual axons of the neurons a dark blue which is visible to the naked eye, even without the use of a microscope.

By visualizing the individual neurons, the team discovered that itch-sensing neurons have large receptive fields. “Receptive fields are the area on the skin that each neuron is responsible for sensing,” Xing explains. “So, if the receptive field is small, such as for touch, you can sense very precisely that something is touching you at this very particular spot. But for the MrgprC11+ itch neurons, we found that they had large receptive fields, three times bigger than for the other neurons we looked at. So that means that when we sense itch, it isn’t confined to a very particular spot. We feel it much more diffusely over a larger area.”

In addition to allowing for the visualization of the itch neurons in the skin, this team’s novel transgenic mouse line also allowed them to learn more about MrgprC11+ neurons in general. For example, they discovered that MrgprC11+ neurons have multiple itch receptors. This is a critical finding according to Xing because “previously nobody was really looking too closely at the MrgprC11+ neurons. Now, that we know that MrgprC11+ neurons are an important itch sensing neuronal population, future researchers may focus significantly more effort on studying MrgprC11+ neurons.”

Genomes are routinely subjected to DNA damage. But most cells have DNA repair systems that enforce genome stability and, ideally, prevent diseases like cancer. The trouble gets serious when these systems break down. When that happens, damage such as unrepaired DNA lesions can lead to tumors, and genomic chaos ensues.

“Double-strand breaks are one of the most dangerous types of DNA damage a cell can experience,” said Chance Meers, a postdoctoral researcher at Columbia University who earned his Ph.D. in molecular genetics in 2019 in the lab of Francesca Storici at the Georgia Institute of Technology. “They inhibit the cell’s ability to replicate its DNA, stalling cell division until the damage is repaired.”

The most accurate pathway of DNA-break repair is by using a homologous DNA sequence to template the re-synthesis of the damaged DNA region. Researchers in the Storici lab previously showed that a homologous RNA sequence could also mediate this break repair, and sought to understand the molecular mechanisms that control this process. They wrote about it in a recently published paper for the journal Molecular Cell.

“This is really about RNA’s capacity to transfer information to DNA that could be used in repairing damage,” explained Storici, professor in the School of Biological Sciences and a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

In a 2014 article published in Nature, her team explained how transcript-RNA could serve as a template for the repair of a DNA double-strand break. In this new study, according to lead author Meers, “we found that not only can RNA serve as a template for the repair of double-strand breaks, but that it was modifying genomic information in the absence of double-strand breaks.”

This modification of DNA even in the absence of an induced double-strand break was very surprising to the team. Also unanticipated, said Meers, was that the process of transferring information depended on the presence of an unexpected enzyme, DNA polymerase Zeta. 

“This is quite surprising, because DNA polymerase Zeta is part of a large class of enzymes known as DNA polymerases characterized by their ability to catalyze the synthesis of DNA molecules from a DNA template,” Meers said.

Polymerase Zeta is part of a subset of DNA polymerases known as translesion DNA polymerases, which have unique properties that allow them to synthesize damaged DNA caused by mutagens like UV radiation. Translesion DNA polymerases also are important in cellular processes like the diversification of B-cell receptors used to recognize foreign elements like viruses.

Meers explained that RNA molecules can be thought of as the cache on a computer – or a short-term memory that is not stably maintained. 

“We use a novel assay in which the yeast chromosomal DNA was genetically engineered to contain a piece of DNA sequence that allows it to be removed only in the RNA that is actively transcribed from the chromosomal DNA, generating a change in the RNA sequence but not in the DNA,” he said. 

If this “short-term memory,” in the form of RNA, is transferred back into the DNA sequence during the process of RNA-templated DNA repair, it becomes “long-term memory” stored in the DNA, which can be thought of as the hard drive.  

“We placed this system into a particular gene in yeast, which gives an observable characteristic trait if this process occurred, allowing us to track the repair process,” Meers said. 

Exploiting such an assay, along with the discovery of a new role for DNA polymerase Zeta in RNA-templated DNA repair and modification, the study contains a series of new findings that helped the team better understand the genetic and molecular mechanisms by which RNA can change DNA sequences in cells.  

This research essentially lays the groundwork for exploring the role that RNA can play in modifying genomic sequence and should allow future studies to more directly explore the role of RNA in genomic instability and, in particular, in other organisms, like humans.

This work was supported by the National Cancer Institute (NCI) and the National Institute of General Medical Sciences (NIGMS) of the NIH (grant numbers CA188347, P30CA056036 and GM136717 to A.V.M.), Drexel Coulter Program Award (to A.V.M.), the National Institute of General Medical Sciences (NIGMS) of the NIH (grant number GM115927 to F.S.), the National Science Foundation fund (grant number 1615335 to F.S.), the Howard Hughes Medical Institute Faculty Scholar (grant number 55108574 to F.S.), and grants from the Southeast Center for Mathematics and Biology (NSF, DMS-1764406 and Simons Foundation, 594594 to F.S.). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF.

CITATION: Chance Meers, Havva Keskin, Gabor Banyai, Olga Mazina, Taehwan Yang, Alli L. Gombolay, Kuntal Mukherjee, Efiyenia I. Kaparos, Gary Newnam, Alexander Mazin, and Francesca Storici. “Genetic characterization of three distinct mechanisms supporting RNA-driven DNA repair and 3 modification reveals major role of DNA polymerase Zeta.” (Molecular Cell, 2020) (https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30554-2

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Writer: Jerry Grillo

Ribonucleotides, units of RNA that can become rooted in DNA during processes such as replication and repair, generally are associated with genomic instability, an increase in mutations, and DNA fragility.

Researchers have been aware of the abundance of ribonucleotides for about a decade, and the lab of Francesca Storici at the Georgia Institute of Technology has been at the forefront, researching the relationship between RNA and DNA in genome stability and instability, and DNA modification. 

“There is much that is unknown about the phenomenon of ribonucleotides in DNA, andit needs to be uncovered,” says Storici, professor in the School of Biological Sciences and a researcher in the Petit Institute of Bioengineering and Bioscience at Georgia Tech, where her lab’s previous studies have led to the development of new-age tools and techniques, to collect and analyze data and answer some of the questions surrounding ribonucleotides.

“It’s important to establish a framework for better directing future studies to uncover physiological roles of ribonucleotides in DNA,” she says. And that’s exactly what she and her colleagues have done in their latest research paper, “Ribonucleotide incorporation in yeast genomic DNA shows preference for cytosine and guanosine preceded by deoxyadenosine,” published recently in the journal Nature Communications.

Namely, they use the tools and techniques they’ve developed over the past few years to characterize sites of ribonucleotide incorporation in DNA, demonstrating clearly that ribonucleotides in yeast DNA are not randomly distributed but show preferences for being incorporated in specific DNA sequence contexts. “We specifically reveal a bias for ribonucleotide incorporation both in yeast mitochondrial and nuclear DNA,” Storici says.

In a previous study published in January 2015, the lab introduced ribose-seq, a high-throughput sequencing technique that allows researchers to establish a full profile of ribonucleotides embedded in genomic DNA, generating large, complex data sets. In late 2018, the lab published its work on a new bioinformatics toolkit called Ribose-Map, which effectively and efficiently transforms the massive amounts of raw sequencing data obtained from the ribose-seq process into summary datasets and publication-ready results.

For their latest work described in Nature Communications, the team deployed ribose-seq to generate the data and Ribose-Map to analyze it, identifying sites of ribonucleotides in yeast DNA and explore their genome-wide distribution. Consequently, the paper’s four co-lead authors included Sathya Balachander (part of the ribose-seq development team and co-author of that paper, now licensing associate for the Bill Harbert Institute for Innovation and Entrepreneurship/University of Alabama-Birmingham) and Alli Gombolay (lead author of the Ribose-Map study).

Contributing equally as co-lead authors of the new research were Taehwan Yang and Penghao Xu, who, like Gombolay, are Ph.D. students in Storici’s lab (where Balachander was a Ph.D. student and postdoctoral researcher).

The team studied three different yeast species and detected a number of similar patterns. In all three species, the deoxyribonucleotide that is immediately upstream of the ribonucleotide was shown to have the greatest impact on the incorporation of ribonucleotides in DNA. “This rule was not clear before,” Storici says. “The study also highlights hotspots of ribonucleotides in DNA sequences containing di- and tri-nucleotide repeats, showing that specific sequence contexts have higher likelihood of ribonucleotide incorporation in DNA. This might be associated with ribonucleotide physiological/pathological functions that are yet to be discovered.”

The lab is now working toward better understanding of how cells control and benefit from ribonucleotide incorporation in DNA by uncovering the patterns and hotspots of incorporation in yeast cells of different genotypes, as well as cells from other species and organisms.

“Now we are interested to see if the rule that we have discovered for yeast applies to other cell types beyond yeast, like human cells for example, and to what extent,” says Storici. “As long term goal, we aim to determine whether there is a sort of language of ribonucleotide incorporation that cells utilize for regulating different cell metabolic functions.”

In addition to those mentioned, other authors of this multi-institutional study were Fredrik Vannberg (former professor in the School of Biological Sciences at Georgia Tech and former Petit Institute researcher), Gary Newnam (manager of the Storici Lab), Anton Bryksin (director of the Petit Institute’s Molecular Evolution Core), Havva Keskin (former Storici grad student, now a researcher with Omega Bio-tek), Kyung Duk Koh (former member of Storici lab, now a researcher at the University of California-San Francisco),  Waleed M. M. El-Sayed (former visiting scholar in the Storici’s lab, now researcher at the National Institute of Oceanography and Fisheries in Egypt), and Sijia Tao, Nicole Bowen, Raymond Schinazi, and Baek Kim from the Emory School of Medicine’s Department of Pediatrics.

For Lewis Wheaton, Black History Month is a special opportunity to recognize African-American culture and history. However, Wheaton celebrates diversity and promotes cultural inclusion all twelve months of the year.

“As far back as I can recall, I was taught to value humanity, love those around you, and learn their perspectives,” says Wheaton, an associate professor in the School of Biological Sciences. “Our society is made great not just because of the wonderful blend of culture that we can see all around us, but in our ability to really value our neighbors.”

In both his personal and professional life, Wheaton takes direct action to improve cultural awareness and consider the interests of wider ranges of humanity.

During conversations with colleagues Manu Platt and Anne Pollock, Wheaton realized a lack of interdisciplinary focus on the relationship between scientific study and social influences. Rather than let their ideas end in conversation, the cohort launched Georgia Tech’s working group on Race and Racism in Contemporary Biomedicine in 2015. Today, the group works with various metro Atlanta Colleges to develop programming addressing race and racism in biomedical research.

When Wheaton leaves Georgia Tech’s campus, he continues to promote diversity and inclusion. And, when it comes to encouraging diversity in one's personal life, Wheaton underscores the importance of taking small daily actions to increase one’s cultural awareness.

“Whether in science, public service as an elected official, or in leadership in societies, I do all I can to ensure that we consider the needs and interests of wider-ranges of humanity,” he says.

With the encouragement of his parents and inspiration from Frederick Douglass, Wheaton says he learned the importance of cultural celebration. Each February he devotes extra attention to the black community, sharing many untold and unappreciated aspects of black culture and history. He also takes the time to learn about and celebrate those various wonderful and beautiful elements.

“We can talk to people that aren’t like us, seek opportunities to welcome people from all backgrounds into our organizations, and we can all support (by way of attendance) celebrations of diversity all around campus, even when we do not belong to that diverse group,” says Wheaton.

To read more about Lewis Wheaton:

Lewis Wheaton: Scientist, Citizen, Councilman

Lewis Wheaton: Success Comes with Responsibility

Unlocking the Mind-Body Connection

More Black History Month Features:

Celebrating Black History Month: The Importance of Representation with Crystal Bell

Celebrating Black History Month: Letting Diversity Shine with Alonzo Whyte

Black History Month: "6Ps" Relevant to Academic and Career Success 

By Grace Pietkiewicz, First-Year Student, School of Literature, Media, and Communication

Two assistant professors from the Georgia Tech College of Sciences, Jenny McGuire and Lutz Warnke, have received 2020 Faculty Early Career Development (CAREER) Awards from the National Science Foundation (NSF).

As NSF's most prestigious award, the CAREER program supports early-career faculty who integrate excellence in education and research, serve as academic role models, and lead advances in the mission of their organization. The award comes with a federal grant for research and education activities for five consecutive years.

“Never underestimate what a National Science Foundation CAREER Award can do for a young scientist,” says Julia Kubanek, College of Sciences Associate Dean for Research. “Many of our senior faculty at Georgia Tech started their funding history as NSF CAREER awardees. They act as a springboard for faculty success in so many ways.”

Kubanek, who is also a professor in Biological Sciences and in Chemistry and Biochemistry, emphasizes the length of the grant: five years. “The funding that comes with an NSF CAREER award provides substantial support to get a faculty member’s fresh and unique research ideas off to a strong start.” The NSF also likes to see research and education combined as a way to inspire creative teaching methods that give students a more hands-on approach.

For Jenny McGuire, assistant professor in Biological Sciences and in Earth and Atmospheric Sciences, the CAREER grant will support paleoecological research exploring how plants and animals respond to environmental change and allow her to test these theories in a deep, ancient cave in Wyoming — where clues left by past environmental shifts could provide insights for current and future climate change.

For Lutz Warnke, assistant professor in Mathematics, the CAREER grant will support fundamental research at the interface of discrete mathematics and probability, exploring the fascinating properties of random networks (or graphs) and their remarkable applications in graph theory, extremal combinatorics, and other areas.

Jenny McGuire: Do Species Track Climate? Paleoecology to Disentangle Niche Dynamics

Since 2015, Jenny McGuire has spent her summers rappelling 30 feet into Wyoming’s Natural Trap Cave, digging for fossils that can provide some insight into the impact past climatic and environmental changes had on plant and animal species 20,000-30,000 years ago. McGuire’s work looks at how those changes in climate might have affected animal migration patterns. 

“I was incredibly excited to get the award, because it is going to allow me to do some really exciting work,” says McGuire, who is also a past NSF Division of Environmental Biology awardee. “My ​project looks at the climate fidelity that different plant and animal species exhibited during past periods of climate change, so that we can characterize the extent to which they will respond to future change. By understanding how species respond to changing climate, we can identify which species and strategies to prioritize to conserve biodiversity going forward.”

Along with increasing our understanding of ecosystem and species-level responses to climate change and drought, McGuire’s spelunking expeditions and research help educate students and communities about how climate affects ecosystems.

Many of McGuire’s cave finds are brought back to Georgia Tech for what she calls Fossil Fridays, when the public is invited to help sift through the gravel and dirt to look for fossils. These “fossil discovery opportunities” reach people from across the broader Atlanta community, as well as East African undergraduate students who participate in workshops facilitated by the Conservation Paleobiology in Africa program.

“We are living in a time of rapid change,” McGuire notes. “Given the extent of the change, it is hard to predict how ecosystems are going to respond by observing snapshots of time. We use organisms' responses to past climatic and environmental changes to determine how things will play out, given the extreme changes that are anticipated.”

Lutz Warnke: Understanding the Evolution of Random Graphs with Complex Dependencies: Phase Transition and Beyond

Lutz Warnke — who is also a recipient of the 2014 Richard-Rado-Prize, the 2016 Dénes König Prize, a 2018 Sloan Research Fellowship, and a NSF Division of Mathematical Sciences award — is fascinated by graph processes and networks, which are useful mathematical abstractions that consist of collections of points with links, or line-segments, connecting them. The more links you add, the more complex those networks become.

“Time-evolving random networks/random graph processes play an important role in several branches of mathematics and applied sciences, including statistical physics, complex networks, and extremal combinatorics,” Warnke says. “Unfortunately, for these processes, there is nowadays a widening gap between simulation-based results and theoretical understanding. I hope to develop new mathematical theory for such random graph processes, in order to better understand their properties, improve existing methods of analysis, and rigorously justify their applications.”

Warnke is using these random graph processes to attack difficult open problems in combinatorics. He explains "they provide a systematic way to give powerful probabilistic guarantees for hard-to-answer deterministic questions, such as the construction of complex graphs with unusual properties/constraints. I am particularly fascinated by the fact that the usage of randomness helps in extremal combinatorics and graph theory, and by developing new ways of analysis/new random processes I am trying to significantly increase the range of combinatorial applications."

The CAREER grant will also allow him to spend more time on the phase transition of random graphs. He explains, “This refers to a sudden change of their typical properties, as we add more and more links to the graph (similar to how the state of water changes as we increase the temperature). I am trying to understand whether the phase transition of a wide variety of random graph processes share essential ‘universal’ features, as predicted by the profound universality paradigm from physics.”

“It is a great honor to receive the NSF CAREER award,” says Warnke. “I gratefully acknowledge this recognition and support from NSF, which will now help/allow me to further advance my research program, and pursue some of the most challenging problems in probabilistic combinatorics.”

McGuire and Warnke are among a number of 2020 NSF CAREER awardees representing Georgia Tech. Learn more about Jenny McGuire and Lutz Warnke, and about the CAREER Program.

Extracting nectar from flowers that may be dancing in the wind requires precise, millisecond timing between the brain and muscles.

By capturing and analyzing nearly all of the brain signals sent to the wing muscles of hawk moths (Manduca sexta), which feed on such nectar, researchers have shown that precise timing within rapid sequences of neural signal spikes is essential to controlling the flight muscles necessary for the moths to eat.

The research shows that millisecond changes in timing of the action potential spikes, rather than the number or amplitude of the spikes, conveys the majority of information the moths use to coordinate the five muscles in each of their wings. The importance of precise spike timing had been known for certain specific muscles in vertebrates, but the new work shows the general nature of the connection. 

“We were able to record simultaneously nearly every signal the moth’s brain uses to control its wings, which gives us an unprecedented and complete window into how the brain is conducting these agile and graceful maneuvers,” said Simon Sponberg, Dunn Family Professor in the School of Physics at the Georgia Institute of Technology. “These muscles are coordinated by subtle shifts in the timing at the millisecond scale rather than by just turning a knob to create more activity. It’s a more subtle story than we might have expected, and there are hints that this may apply more generally.”

The research was reported Dec. 16 in the journal Proceedings of the National Academy of Sciences. The work was supported by the National Science Foundation, the Esther A. & Joseph Klingenstein Fund, and the Simons Foundation.

Researchers Joy Putney, Rachel Conn and Sponberg set out to study how the brain coordinates agile activities such as running or flying that require compensating for perturbations in the air or variations on the ground. While the size of the signals could account for gross control of the behavior, the fine points of choreographing the tasks had to come from elsewhere, they reasoned.

Recording motor control signals in humans and other vertebrates would be a daunting task because so many neurons are used to control so many muscles in even simple behaviors. Fortunately, the researchers knew about the hawk moth, whose flight muscles are each controlled by a single or very few motor neurons. That allowed the researchers to study neural signals by measuring the activity of the corresponding muscles, using tiny wires inserted through the insect’s exoskeleton.

Putney and Conn determined the location of each wing muscle inside the moth exoskeleton, and learned where to create tiny holes for the wires — two for each muscle — that capture the signals. After inserting the wires in the anesthetized moths, the graduate students closed the holes with superglue to hold the wires in place. Connections to a computer system allowed recording and analysis.

“The first time I did the surgery by myself, it took six hours,” said Putney. “Now I can do it in under an hour.”

While connected to the computer, the moths were able to fly on a tether as they viewed a moving 3D-printed plastic flower. To measure the torque forces the moths created as they attempted to track the flower, the wired-up moths were suspended from an accelerometer.

The torque information was then correlated with the spiking signals recorded from each wing muscle.

The importance of the work relates to the completeness of the signal measurement, which brought out the importance of the timing codes to what the moth was doing, Putney said.

“People have recorded lots of muscles together before, but what we have shown is that all of these muscles are using timing codes,” she said. “The way they are using these codes is consistent, regardless of the size of the muscle and how it is attached to the body.”

Indeed, researchers have seen hints about the importance of precision timing in higher animals, and Sponberg believes the hawk moth research should encourage more study into the role of timing. The importance and prevalence of timing across the moth’s motor program also raises questions about how nervous systems in general create precise and coordinated motor commands.

“We think this raises a question that can’t be ignored any longer — whether or not this timing could be the real way that the brain is orchestrating movement,” Sponberg said. “When we look at specific signals in vertebrates, even up to humans, there are hints that this timing could be there.”

The study could also lead to new research on how the brain produces the agile motor control needed for agile movement.

“Now that we know that the motor control is really precise, we can start trying to understand how the brain integrates precise sensory information to do motor control,” Sponberg said. “We want to really understand not only how the brain sets up signals, but also how the biophysics of muscles enables the precise timing that the brain uses.”

This material is based upon work supported by National Science Foundation Graduate Research Fellowships DGE-1650044 and DGE-1444932, an NSF CAREER award (1554790), and a Klingenstein-Simons Fellowship Award in the Neurosciences. 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 organization.

CITATION: Joy Putney, Rachel Conn, and Simon Sponberg, “Precise timing is ubiquitous, consistent and coordinated across a comprehensive, spike-resolved flight motor program.” (Proceedings of the National Academy of Sciences, 2019.) https://www.pnas.org/content/early/2019/12/11/1907513116

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While it’s largely business as usual in Cobb’s cities following Tuesday’s municipal elections, Smyrna’s government faces significant change....It would also mean newcomer Lewis Wheaton, a 42-year-old Georgia Tech professor who won 57% of the preliminary vote in the Ward 7 race, would be the only person of color on the council.

At Georgia Tech, members and trainees of the Center for Microbial Dynamics and Infection discuss the identification of pathogen essential genes during coinfections, and how coral management can improve coral defenses against pathogens. Guests were Marvin Whiteley, Gina Lewin, Deanna Beatty, Mark Hay, and Frank Stewart.

Fire ants build living rafts to survive floods and rainy seasons. Georgia Tech scientists are studying if a fire ant colony’s ability to respond to changes in their environment during a flood is an instinctual behavior and how fluid forces make them respond. Hungtang Ko and David Hu will present the science behind this insect behavior, focusing their discussion on how the living raft changes size under various environmental conditions at the American Physical Society’s Division of Fluid Dynamics 72nd Annual Meeting on Nov. 26.

By A. Maureen Rouhi

Examine your hands. The right is a mirror image of the left. They look very similar, but you know they’re not when you try to put your left hand inside a right glove.

The molecules of life have a similar handedness. Proteins for example are like your left hand, made up of amino acids that are all left-handed. This phenomenon is called chirality. How chiral systems emerged is one of the key questions of origins-of-life research.

Many explanations have been proposed. Now a Georgia Tech team examining the problem suggests that stability is what drove the emergence of chiral systems. Led by Jeffrey Skolnick, a professor in the School of Biological Sciences, the team includes  research scientists Hongyi Zhou and Mu Gao. The work was supported in part by the Division of General Medical Sciences of the National Institutes of Health (NIH Grant R35-118039) and published on Dec. 10, 2019, in PNAS.

They reached their conclusion from computer simulations examining the stability and properties of a prepared protein library made up of  

• nonchiral proteins, containing a 1:1 ratio of right- (D) and left-handed (L) amino acids, also called demi-chiral;  
• nonchiral proteins containing 3:1 and 1:3 of D and L amino acids; and
• chiral proteins containing all D and all L amino acids. 

Their simulations showed that nonchiral proteins, even the demi-chiral ones, have many properties of chiral proteins. They fold and form cavities just like ordinary proteins. They could have performed many of the biochemical functions of ordinary proteins, especially the most ancient and essential ones. These nonchiral proteins also can adopt the structures of contemporary proteins including ribosomal proteins, necessary for protein transcription.

“This ability of nonchiral proteins to fold and function might have been an essential prerequisite for the life on Earth,” says Eugene Koonin, a senior investigator at the National Center for Biotechnology Information, in the National Institutes of Health. “If so, this result is a truly fundamental finding that contributes to our understanding of the origins of life.”

However, nonchiral proteins have fewer hydrogen bonds than those made of all D or all L amino acids. The demi-chiral ones have the fewest. Thus chiral proteins are much more stable than demi-chiral ones. “The biochemistry of life as we know it likely results from stability driven by hydrogen bonds,” says Skolnick, who is a member of the Parker H. Petit Institute of Bioengineering and Bioscience.

The PNAS study examines the properties of proteins from the point of view of physics alone, without the intervention of evolution, Skolnick says. “It explains how the chemistry of life emerged from basic physical principles. It also strongly suggests that simple life might be quite ubiquitous throughout the universe.”

“I wish to understand how life emerged and to know its design principles,” Skolnick says. “On the most academic level, I wish to explain the origin of life based on physics with well-defined testable ideas.”

The newly published “work offers a non-intelligent-design perspective as to how the biochemistry of life might have gotten started,” Skolnick says. “It shifts the emphasis from evolution to the inherent physical properties of proteins. It removes that chicken-and-egg quandary that chiral RNA is required to produce chiral proteins. Rather, such excess chirality is shown to emerge naturally from a nonchiral system.”

What the work does not address is why L-amino acids and L-proteins emerged dominant on Earth. It is know that some meteorites have an excess of L-amino acids. “If one assumes that many primordial amino acids were seeded by meteorites, many of them have an excess of L over D amino acids,” Skolnick says. “All it would take is just a little bias to get the whole process started.”

Skolnick says the next step is to test the computer simulations by studying the emergent chemistry of nonchiral proteins.  A key unanswered question is how did replication emerge? “We can explain life’s biochemistry and many of the parts associated with replication from this study, but not replication itself,” he says. “If we can do this, then we have all of life’s components. If this works, ultimately I want to recreate what could be the early living systems in a test tube.”