Gavin Palowitch honored with the
Fred Wedler Outstanding Doctoral Dissertation Award
Gavin Palowitch, a graduate student within Penn State’s Biochemistry, Microbiology, and Molecular Biology (BMMB) program, was recognized as the 2021 recipient of the Fred Wedler Outstanding Doctoral Dissertation Award.
Each year, the Department of Biochemistry and Molecular Biology, selects one doctoral student to receive the award. It is given to the student whose dissertation is judged to be the best, based on evaluation criteria given to the student’s dissertation committee. Each student defending a doctoral dissertation is automatically considered for the award.
While a graduate student Penn State’s BMMB program, Gavin worked within the laboratory of Associate Professor of Chemistry and of Biochemistry and of Molecular Biology, Amie Boal. Gavin’s dissertation research focused on the characterization of metalloenzymes, specifically the enzyme ribonucleotide reductase (RNR). The goal of his research was to understand new ways that nature has adapted microbial class I RNRs, while also elucidating the chemistry behind the assembly processes of these novel cofactors. RNR is essential for all forms of life because it catalyzes the formation of deoxyribonucleotides, the building blocks of DNA. The essential nature of RNR’s makes the enzyme a potential drug target.
All known class I RNRs require a binuclear metal cofactor in the β (beta) subunit of the enzyme, activated in an oxygen-dependent reaction to form a potent oxidant that drives reaction with the ribonucleotide substrate in the α (alpha) subunit of the enzyme. The recent discovery of novel cofactors among class I RNRs highlights the diverse strategies that organisms use to replicate their DNA in specialized environmental niches. Bacterial pathogens may also adapt the cofactors employed by their RNRs to survive within an animal host.
By identifying how RNRs from pathogenic bacteria works differently from the enzyme in our human body, Gavin, and the Boal group, hope to be able to target and block the function of certain bacterial enzymes, thereby preventing the bacteria from being able to replicate and cause disease. Gavin’s research primarily focused on systems found in pathogenic and commensal bacteria in humans and identifying how they function differently from the human form of the enzyme. “We hope that this research will allow for the development of therapeutics that can target these harmful bacteria selectively and avoid side effects by not targeting the human form of the enzyme,” said Gavin. “My research could also enable development of a new class of antibiotic therapeutics, as a potential solution to the emerging issue of antibiotic-resistant bacteria in healthcare settings.”
Since being named as the recipient of the Fred Wedler Outstanding Doctoral Dissertation Award, Gavin successfully defended his thesis and earned his Doctor of Philosophy (Ph.D.) degree in May of 2021. He now works as a Scientist of Structural Biology at Foghorn Therapeutics, a biotechnology company based in Cambridge, Massachusetts. “My role at Foghorn is to provide structural biology knowledge and expertise to several project teams, with the goal of developing therapies for people suffering from rare and difficult-to-treat diseases,” says Gavin. “My role encompasses everything from protein construct design to solving x-ray crystal structures of our target proteins, which aids in structure-based drug design.”
Gavin’s project involved collaboration with other research groups including the Bollinger-Krebs and Silakov groups at Penn State. “This type of open and fully collaborative environment was an incredible space to learn in and grow as a junior scientist,” says Gavin. “My dissertation research in the Boal group and experience at Penn State prepared me extremely well for my current position at Foghorn.”