My laboratory is interested in understanding the regulation of gene expression at the molecular level. Our primary tool is cryo-electron microscopy (cryo-EM). We use cryo-EM to study the atomic details of snapshots of our macromolecular machines of interest in action. We have revealed exciting insights into the structure and function of macromolecular machines and assemblies involved in (1) protein production and (2) genome editing. We will continue to apply cryo-EM as well as other tools in our repertoire, including site-specific labeling and conformational analysis using negative stain EM, to produce mechanistic insights into the structure and function of macromolecular machines involved in gene regulation, broadly-defined. In the next five years, my lab plans on elucidating the molecular architectures that set the foundation for accurate gene expression and production of proteins, the workforce of the cell. Combined with the work on CRISPR genome-engineering complexes, these results will have major implications for researchers performing translational research to combat a myriad of diseases.