Protein-nucleic acid interactions are key to many fundamental life processes. The primary focus of our lab is to characterize the protein-DNA-RNA interactions of the bacterial and archaeal immune system, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR is an RNA-based adaptive immune system that inactivates foreign DNA and/or RNA entering the cell, based on the sequence similarity of small RNAs, called CRISPR RNA (crRNA) to the invading genetic element. The process requires several proteins called CRISPR associated (Cas) proteins. The CRISPR-Cas9 system has revolutionized the genome editing field due to the ease with which targeted double-stranded DNA breaks can be achieved in cells, using a guide RNA and Cas9 protein.
The long-term goals of our laboratory are to understand how CRISPR-Cas systems enhance the pathogenicity and virulence of bacteria, and to determine the protein-DNA interactions essential for adaptation, the process by which bacteria and archaea insert a piece of phage DNA into the CRISPR locus. Another research focus is to characterize the conformational steps in the nucleic acid induced activation of Cas9. We incorporate molecular biology, biochemistry, X-ray crystallography, bioinformatics, and additional biophysical tools to study CRISPR-Cas systems. In addition, we collaborate with Dr. Peter Z. Qin at the University of Southern California for Electron Paramagnetic Resonance studies.