B.S., 1998, Kerala Agricultural University, Kerala, India
Ph.D., 2007, Ohio State University
Postdoc, 2007-2013, Northwestern University, Evanston, Illinois
Research Associate, 2013-2014, Northwestern University, Evanston, Illinois
protein-nucleic acid interactions, CRISPR-Cas systems, structural biology, gene editing, CRISPR adaptation
Mechanisms of CRISPR-Cas Systems
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-Cas (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR-associated). CRISPR-Cas 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 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 decipher the atomic interactions and conformational changes of Cas protein-nucleic acid complexes to enable development of high-fidelity CRISPR-Cas systems for genome applications. Towards this, we are focusing on the structure and mechanisms of Cas9 and Cas12a, two proteins that are widely used for genome applications and diagnostics purposes. Another area of focus is determining the protein-DNA interactions essential for site-specificity during CRISPR adaptation, the process by which bacteria and archaea insert a piece of the intruder genome into the CRISPR locus to offer future immunological protection against that specific intruder. We also are interested in understanding alternate functions of CRISPR systems in bacterial physiology, for example, the contributions of CRISPR-Cas systems towards enhancing the pathogenicity and virulence of bacteria. We incorporate molecular biology, biochemistry, X-ray crystallography, bioinformatics, and additional biophysical and computational tools to study CRISPR-Cas systems.