BDC Special Seminar: Jesse Zalatan

Challenges and Opportunities for Bacterial Transcriptional Reprogramming with CRISPR-Cas Activators

Speaker: Jesse Zalatan, PhD

Assistant Professor, Chemistry, Biological Chemistry and Enzymology
University of Washington

Abstract
CRISPR activation/inactivation (CRISPRa/i) has been widely used to regulate gene expression in eukaryotic cells, but applications in bacterial systems remain limited. We have developed a new bacterial CRISPRa system that enables robust, programmable activation and repression of multiple genes simultaneously with a large dynamic range of gene expression. We identified multiple features of bacterial promoters that impose stringent requirements on CRISPRa-mediated gene activation, which may explain why gene activation systems in bacteria have lagged behind eukaryotic systems. We further describe strategies to improve and generalize synthetic gene regulation in bacteria. These methods lay the groundwork for more widespread use of bacterial CRISPRa in basic research and practical applications including functional genomics screens and metabolic engineering.

Short Bio
Jesse Zalatan is an Assistant Professor of Chemistry at the University of Washington. His research focuses on understanding the physical organizing principles of biological networks in systems such as cell signaling, metabolism, and gene regulation, using methods ranging from mechanistic enzymology to synthetic biology. Jesse did his graduate work with Dan Herschlag on the mechanisms of enzyme-catalyzed phosphoryl transfer reactions. He performed postdoctoral research with Wendell Lim, where he studied mechanisms for controlling specificity in cell signaling networks.