Structure & Function of Nucleic Acid Sensors

The evolutionary back and forth between hosts and mobile genetic elements drives the innovation of remarkable molecular strategies to sense or conceal foreign genetic material. The Knott Lab uses bioinformatics, biochemistry, and structural biology to understand how CRISPR-Cas and other novel immune systems specifically sense DNA or RNA. We aim to better understand the function of nucleic acid sensors to harness their activity as tools for molecular diagnostics or as innovative biomedicines.

The proposed project will involve mining available metagenomic data to expand on and discover novel immune systems that specifically target RNA. Students will have the opportunity to explore bacterial and phage metagenomes to compile datasets of interesting RNA sensors. Students will use these datasets to generate large multiple sequence alignments and phylogenetic trees to reveal associations between existing and novel RNA sensors. The resulting datasets will uncover potentially novel and exciting nucleic acid sensors and serve as the foundation for subsequent biochemical experiments to assay function.