Protein-Nucleic Acid Interactions
Protein-nucleic acid interactions are key to fundamental life processes such as DNA replication, transcription, recombination, and protein synthesis. Deciphering the mechanism of protein-nucleic acid interactions is invaluable for understanding human disease pathways and infections. The primary focus of my lab is to characterize protein-DNA/RNA interactions structurally, biochemically, and biophysically. The immediate emphasis is the study of the recently discovered bacterial and archaeal immune system, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR is an RNA-based adaptive immune system that inactivates foreign DNA/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 my laboratory are to understand the role of CRISPR/Cas system in pathogenicity and virulence of bacteria, characterize the mechanism of adaptation of bacteria to phage infection, and to determine the signaling mechanisms of the CRISPR/Cas system. We incorporate molecular biology, biochemistry, X-ray crystallography, and additional biophysical tools to characterize these protein-nucleic acid interactions.
crRNA-Cas protein complex inactivates invading genetic element.
Model of Topoisomerase V, a DNA modifying enzyme, bound to DNA.
Active site residues of Topoisomerase V interacting with a modeled DNA.
Research keywords: Protein-Nucleic acid interactions; CRISPR; structural biology