Eli Lilly Award in Biological Chemistry

Professor Yimon Aye, École Polytechnique Fédérale de Lausanne (EPFL)

For outstanding research in biological chemistry of unusual merit and independence of thought and originality.

Professor Yimon Aye is the recipient of the 2020 Eli Lilly Award in Biological Chemistry. Her receipt of this award reflects the broad ramifications of her multifaceted research program on both chemistry and biology. Science in the Aye lab seeks to understand various non-canonical cellular communication processes. The Aye lab is most well-known for studies into electrophile signaling, a nuanced communication mode whereby chemically-reactive molecules directly modify select target proteins, leading to alteration of their function. Her lab is also well-known for investigations into nucleotide signaling pathways regulated by ligand-stimulated changes in protein–protein associations that are of importance in genome operation.

The work from the Aye lab is thus slowly bringing both eclectic forms of cellular communication into focus. She has pioneered the ingenious use of photocaged electrophiles (REX technologies) to bypass many of the limitations associated with the use of reactive electrophiles in cells and, unusually, whole organisms. The initial application of REX technologies was to studying individual-protein-specific electrophile signaling. This work introduced several new concepts into the chemical biology canon, including breaking the tether, and pseudo-intramolecular transfer. Thus, her method, T-REX, allowed essentially native, electrophile-modified states of electrophile-sensor proteins to be generated on demand in cells and model organisms. For the first time, their specific signaling functions could be assayed and identified. Her work established that, even at low ligand-occupancy, electrophile signaling can rewire cellular decision-making processes. A change in protocol, but not the caging strategy, further allowed global assaying of electrophile sensing in specific organelles, or tissues. This approach has unearthed novel electrophile sensors that have been assessed by T-REX. Through a united team effort, the Aye lab is striving to develop novel interventions, and to better understanding of current drugs through active collaborations with industrial scientists.

In parallel, Aye also uses biochemistry/cell biology/genetics to uncover novel roles of one of the most ancient enzymes, ribonucleotide reductase (RNR). This enzyme is intrinsically tied to growth and life itself, as it is the source of nucleotide-pools essential for genome operation. However, RNR has also had unexpected behaviors in that it is a known suppressor of growth, particularly in tumors, where it is proposed to be a tumor suppressor. The Aye lab recently uncovered a signaling axis involving the large subunit of RNR as a direct inhibitor of a protein that promotes genome replication, ZRANB3. Further studies are starting to uncover how this axis plays a role in tumor formation and prevention, and how to control this pathway.

Pfizer Award in Enzyme Chemistry

Professor Rahul Kohli, University of Pennsylvania

For outstanding work in enzyme chemistry where the presence of enzyme action is unequivocally demonstrated.

Professor Rahul Kohli is the recipient of the 2020 Pfizer Award in Enzyme Chemistry. Against the backdrop of ever-increasing sequencing data, the Kohli Lab is inspired to understand not simply what information is encoded in genomes, but how this information can change. Dr. Kohli’s motivation for studying the “dynamic genome” is rooted in his experience as a physician-scientist. Affinity maturation of antibodies, epigenetic transformations promoting cancer, and the acquisition of antibiotic resistance – representative processes that shape the disease course of his patients – all involve modification or mutations of genomic DNA. Using the combined approaches of enzymology and chemical biology, the lab has set about trying to understand enzymes that naturally target and modify the genome with relevance to immunity, epigenetics, and infectious pathogenesis.

Dynamic modifications to cytosine in the mammalian genome are one major focus of the lab, given that methylation, deamination, and oxidation all intersect at this base. Mechanistic work from the Kohli lab helped shape the current model for how 5-methylcytosine (5mC) marks can be erased from the genome to reactivate silenced genes. For example, their biochemistry on AID/APOBEC DNA deaminases moved the field away from the idea of deamination-based cytosine demethylation pathways and towards oxidation-based mechanisms. As this bona fide DNA demethylation pathway involves the generation of genomic 5-hydroxymethylcytosine (5hmC) from 5mC by TET family dioxygenases, the Kohli lab has developed activity-based probes to capture TET activity, and has advanced novel non-destructive, enzymatic methods for mapping 5hmC at base resolution. In lock-step with these efforts centered on cytosine modification in mammalian genomes, the Kohli lab has also worked to understand molecular mechanisms that contribute to genome-diversification and antibiotic evasion in bacteria. The lab has focused on the key enzymatic axis that regulates the DNA damage or “SOS response” in bacteria. The lab has revealed molecular mechanisms governing SOS activation and has derived inhibitors that can potentially be used to combat the evolution of antibiotic resistance. With a stronger mechanistic understanding of DNA modification and mutation, work from the Kohli lab is being harnessed to access the biotechnological and medical potential of genome-altering processes.

The Repligen Award in Chemistry of Biological Processes

This award is no longer supported.  Division members are working to establish new funding in order to continue this tradition honoring luminary biochemists who have shaped our field.  If you would be willing to help, or know of possible sources of support for this long-standing award, please contact the division via Wayne Outten (OUTTENF@mailbox.sc.edu) or Anne-Frances Miller (afmill3r2@gmail.com).  Thank you.

Gordon Hammes ACS Biochemistry Lectureship

Professor Dan Kahne, Harvard University

For outstanding contributions in scientific research at the interface of chemistry and biology, particularly in the realm of biochemistry, biological chemistry and molecular biology.

Professor Dan Kahne is the recipient of the 2019 Gordon Hammes ACS Biochemistry Lectureship. The Gordon Hammes Lecture Award is sponsored jointly by Biochemistry and the ACS Division of Biological Chemistry. The objective is to recognize and honor a single individual whose scientific contributions have had a significant impact on research at the interface of chemistry and biology. This year’s award goes to Professor Dan Kahne of Harvard University.

Professor Kahne trained with Gilbert Stork at Columbia University and started his independent career as a synthetic chemist where he developed a novel method to make glycosidic linkages for use in complex carbohydrate synthesis. His laboratory has a long-standing interest in natural products and their targets. They were the first to develop synthetic methods to change the natural carbohydrates attached to vancomycin, allowing them to make derivatives of vancomycin that kill vancomycin-resistant bacteria. These studies of glycopeptide antibiotics led to a longstanding quest to understand the extracellular steps of cell wall synthesis in detail. They have synthesized the lipid-linked oligosaccharide building blocks of peptidoglycan and developed sophisticated assays to study the penicillin binding proteins that polymerize and crosslink peptidoglycan. Since both Gram-positive and Gram-negative bacteria are surrounded by peptidoglycan, which is essential for survival, it is a major target for antibiotics. Many of the tools they have developed are useful to both discover new antibiotics and to dissect their mechanism of action.

In addition to expertise in synthesis and mechanistic studies of antibiotics, the Kahne group has considerable understanding of the physiology of Gram-negative bacteria. Gram-negative bacteria depend for their survival on having an intact outer membrane. It is the defining piece of physiology that differentiates Gram-negative from Gram-positive organisms and its presence serves as an effective permeability barrier that prevents penetration of most drugs. This outer membrane is assembled by several multi-protein machines, and his group identified many of the genes responsible for inserting beta-barrel proteins into the outer membrane as well as several of the genes involved in assembling lipopolysaccharide on the cell surface of this outer membrane. His lab has purified the components of both multi-protein complexes and reconstituted their activity in vitro in proteoliposomes, opening the door for detailed biochemical analysis. They are now in a position to use these tools as part of a program to discover inhibitors of outer membrane biogenesis, which would make the cells leaky. Such OM assembly inhibitors could be effective alone or used in combination with known antibiotics to treat problematic Gram-negative infections (ESKAPE pathogens).

Kahne will present a talk and receive his award during the Gordon Hammes ACS Biochemistry Symposium at the 258th ACS National Meeting & Exposition, held in San Diego, Aug. 25-29, 2019.

Gordon Hammes ACS Biochemistry Scholar Award

Professor Kathleen Leamy, Gonzaga University

To honor the young scientists responsible for the very best papers published in Biochemistry.

Professor Kathleen Leamy is the recipient of the 2019 Gordon Hammes Scholar Award. The Gordon Hammes Scholar Award honors the young scientists responsible for the very best papers published in Biochemistry. Established in 2017 and awarded alongside the Gordon Hammes Lectureship Award, the Scholar Award seeks to recognize those at the bench – graduate students, postdocs, and undergraduates – for the outstanding work they do. The award is sponsored jointly by Biochemistry and the ACS Division of Biological Chemistry. Professor Leamy of Gonzaga University was selected as this year’s winner from a large applicant pool based on her first-author paper, “Molecular Mechanism for Folding Cooperativity of Functional RNAs in Living Organisms,” published earlier this year.

Kathleen Leamy grew up in New York State and received her bachelor’s degree from Siena College, with majors in chemistry and biochemistry.  While at Siena College she did research with Dr. Daniel Moriarty and Dr. Jodi O’Donnell, where she studied natural product antibiotics and porphyrin thin films sensors.  Kathleen completed her doctoral degree at The Pennsylvania State University under the direction of Dr. Philip Bevilacqua, studying the folding and adaptation of functional RNAs. She is currently an assistant professor in the Department of Chemistry and Biochemistry at Gonzaga University.

Leamy will present a talk describing her research and receive her award during the Gordon Hammes ACS Biochemistry Symposium at the 258th ACS National Meeting & Exposition, held in San Diego, Aug. 25-29, 2019.

The ACS Chemical Biology Lectureship

Professor Chuan He, University of Chicago

For contributions that have had a major impact on scientific research in the area of Chemical Biology.

The 2019 ACS Chemical Biology Lectureship Award was presented to Professor Chuan He. The award is sponsored jointly by ACS Chemical Biology and the ACS Division of Biological Chemistry. Professor He is the John T. Wilson Distinguished Service Professor in the Department of Chemistry and Department of Biochemistry and Molecular Biology at the University of Chicago. His recent accomplishments are vast. In 2011, his group discovered reversible RNA methylation as a new mechanism of gene expression regulation at the post-transcriptional level. Since then, he has been selected as an investigator of the Howard Hughes Medical Institute (2013), leads Chicago’s first Center for Excellence in Genomic Science (2016), and was one of three recipients of the Paul Marks Prize for Cancer Research from Memorial Sloan Kettering (2017).

Professor He received his Bachelor of Science degree in 1994 from the University of Science and Technology of China and his Ph.D. in Chemistry from the Massachusetts Institute of Technology in 2000. After training as a Damon-Runyon postdoctoral fellow at Harvard University, he joined the University of Chicago as an assistant professor, rising to associate professor in 2008 and full professor in 2010. His recent research concerns reversible RNA and DNA methylation in biological regulation. His laboratory has spearheaded the development of enabling technologies to study the biology of 5-hydroxymethylcytosine (5hmC) in mammalian genomes. Dr. He presented his work on April 2, 2019 at the 257th ACS National Meeting and Exposition held in Orlando, Florida.

The Biopolymers Murray Goodman Memorial Prize

Professor David Beratan, Duke University

For outstanding accomplishments in one or more of the areas of biochemistry, biophysical chemistry, biophysics, and/or chemical biology.

Professor David Beratan is the recipient of the 2018 Biopolymers Murray Goodman Memorial Prize for his seminal contributions to the field of electron transfer in biological systems. Dr. Beratan is currently the R. J. Reynolds Professor of Chemistry in the Department of Chemistry at Duke University and holds Professorships in the Departments of Physics and Biochemistry at Duke. He is also an Adjunct Professor in the Department of Chemistry of the University of Pittsburgh. Gaining an undergraduate degree in chemistry from Duke University and a Ph.D. from California Institute of Technology, Professor Beratan went on to work at NASA’s Jet Propulsion Laboratory and the University of Pittsburgh before returning to Duke in 2001.

Professor Beratan’s theoretical insights into tunnelling pathways of electron transfer in biological macromolecules established physical principles that have been extended to understand the phenomenon in a wide range of systems. His research group works closely with experimentalists and some of the current foci are designing molecular structures and assemblies for solar energy capture and conversion, exploring charge transfer mechanisms in bacterial nanowires and designing de novo proteins to explore proton-coupled electron transfer mechanisms. Professor Beratan presented his work in April 2019 at the 257th ACS National Meeting and Exposition held in Orlando, Florida.