Research in my laboratory focuses on the molecular basis of the processes that relate to protein nucleic acid interaction. The strategy that we use is based primarily on structural studies using X-ray crystallography, for which I have extensive training. A central premise of our work is that in order for structural studies to provide understanding of these processes we must know the structure of the entire assembly that executes the process, captured at each step in the process. From such studies we derive mechanistic models relating the physical features and chemistry of proteins and nucleic acids to their function. Interrogation of these models using mutagenesis, biochemistry and cell-based techniques further relates structure to function and provides a more complete molecular description of the process at hand.

Most recently my laboratory focuses on the CRISPR-Cas system, a RNA-based adaptive immune system found in bacteria that protects against invasion by viruses and plasmids. Mechanistic studies of the CRISPR-Cas system is contributing to ongoing efforts aimed at exploiting this system to both protect domesticated bacteria (such as those used in food and pharmaceutical production) and combat human pathogens and the spread of antibiotic resistance. Moreover, RNA-guided nucleases from the CRISPR-Cas system are currently being adapted for genome editing and regulation strategies in a wide variety of organisms, including humans. Indeed, the potential of the CRISPR-Cas toolkit is just being realized and studies centered on understanding how the CRISPR-Cas systems function represents an important need. To this end, my laboratory has provided structural and mechanistic insight into how CRISPR-Cas systems identify and cleave their DNA targets.