Imaging macromolecular machines in gene regulation

Research in my laboratory is focused on understanding the structure and function of macromolecular machines using cryo-electron microscopy (cryo-EM). There are three broad avenues of investigation: (1) mechanisms of RNA-guided CRISPR-Cas surveillance (2) methods to solve structures of human complexes in a highly parallel manner, and (3) understanding nucleic acid processing machines, including ribosomes and RNA polymerases. We are fundamentally interested in understanding how molecular machines are assembled and perform their myriads of functions. We use multidisciplinary approaches to perform detailed mechanistic studies that, in the end, lead to high impact work and broad applications. Here, I propose how our approach of studying basic enzymology will lead to important insights into (a) how Cas9 can function as a multi- turnover enzyme, (b) how PRIME editors recognize and edit DNA targets, (c) the structure and function of retrons, and (d) determining the mechanisms of novel antiviral defense systems in bacteria.