The main research focus of our group is to understand how small regulatory RNA or DNAmediates prokaryotic defense against invasion by foreign nucleic acids. The main focus of my work is to systematically demonstrate the mechanisms of 1) the CRISPR-Cas system and 2) Argonaut (Ago) protein-mediated RNA/DNA interference.

►CRISPR-Cas systems

The clustered regularly interspaced short palindromic repeats (CRISPR), together with CRISPR-associated (Cas) proteins form the microbial adaptive immune system that protects against invading phages and plasmids. The CRISPR-Cas system is a RNA-guided immune system found in nearly half of all bacteria studied, as well as in the majority of archaea. Our research in this area includes the molecular mechanism of spacer acquisition, pre-crRNA processing and RNA-guided DNA/RNA cleavage.The overall goal of our studies of the CRISPR-Cas system is to gain important insights into the structural-functional relationship of the processes prokaryotes use to fight invading nucleic acids.

►Ago protein-mediated DNA interference

RNA interference is a conserved biological response to double-stranded RNA that regulates gene expression. The response is mediated by small interfering RNAs (siRNAs), which guide the sequence-specific degradation of cognate messenger RNAs (mRNAs).Ago protein is a key component in the RNA interference pathway. Recent bioinformatics analyses suggest that prokaryotic Ago plays a number of critical roles in the anti-viral defense system of bacteria. Unlike its eukaryotic counterpart where mRNA interference is mediated by siRNA, several pAgo proteins have been shown to perform either RNA-guided or DNA-guided interference of DNA.Our long-term goals are to structurally characterize and mechanistically define events associated with RNA or DNA interference.