Jerome Fox, Assistant Professor of Chemical and Biological Engineering, University of Colorado, Boulder.
Systems Biocatalysis for Drug Discovery and Chemical Production
Cells rely on complex networks of interacting catalysts to regulate the biochemical processes that allow them to grow and survive in dynamic environments. Efforts to control these networks—or to predict system-wide behaviors—require an understanding of the structural and kinetic relationships that allow enzymes to collaborate within them. In this presentation, I will discuss my group’s efforts to use synthetic biology, optogenetics, and mathematical modeling to dissect—and then, rewire—biocatalytic systems responsible for two disparate processes: phosphorylation-mediated signaling in mammalian cells and oleochemical production in Escherichia coli. The talk begins with a single enzyme: protein tyrosine phosphatase 1B (PTP1B), a broadly important regulatory protein and an elusive drug target for type II diabetes, obesity, and breast cancer. Guided by detailed biophysical studies, my group has developed new approaches for placing this enzyme under optical control and for using microbial systems to guide the discovery and assembly of targeted inhibitors. The presentation shifts gears by examining a biocatalytic assembly line: the fatty acid synthase (FAS). Using detailed models of FAS activity, we have developed nonintuitive strategies for controlling fatty acid synthesis in microbial hosts. The results of our work show how evolutionary constraints on the structures of biomolecules can guide the design of tunable biocatalysts and biologically active agents. We will discuss applications in drug development and chemical production.
Jerome joined the University of Colorado, Boulder in January of 2016 as an Assistant Professor of Chemical and Biological Engineering. He completed his PhD in chemical engineering with Doug Clark and Harvey Blanch at the University of California, Berkeley in 2012, and he received a BS in environmental engineering from Johns Hopkins University in 2007. Prior to joining CU, he was a postdoc in the lab of George Whitesides at Harvard University, where he carried out research on molecular recognition, complex systems, and optical metamaterials. At CU, his lab focuses on the development of new methods to engineer biocatalytic networks for the discovery and synthesis of functional molecules (e.g., fuels, dyes, or pharmaceuticals) and the design of new classes of synthetic systems.