Nucleic Acid Immune Sensors

Bacteria are embroiled in a constant struggle with virulent bacteriophages. This battle for survival spans millions of years of evolution. Throughout this struggle, bacteria and phages have evolved remarkably diverse strategies to protect themselves or to evade immune recognition. Our work seeks to describe how diverse bacterial machinery, including CRISPR, discriminate self from non-self to protect against phage infection. We aim to better understand the mechanisms of diverse immune systems to enable the development of next-generation tools and CRISPR therapeutics. Our research projects explore the structure and function of programmable CRISPR systems in addition to novel innate immune systems that specifically target nucleic acids such as RNA. Using structural biology (cryo-EM, X-ray crystallography) and biochemistry, we seek to understand, down to atomic resolution, how these complexes sculpt, scaffold, and modify RNA. Current projects have the opportunity to use biochemistry and structural biology to discover how CRISPR enzymes function at the molecular level, an understanding that will improve our ability to apply them as diagnostics for Influenza, HIV, and SARS-CoV-2 viral infection. We are also studying other unique CRISPR systems that target RNA using cryo-EM and RNA biochemistry to drive therapeutic tool development. For more information about specific projects see our lab website: www.theknottlab.org