Determining the Structure and Function of Newly Discovered Immune Systems

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Project Summary Basic research on newly discovered immune systems has led to the development of important molecular tools for use in science and medicine. For example, eukaryotic antibodies are used to diagnose and treat disease, prokaryotic restriction enzymes are used to manipulate DNA sequences in vitro, and prokaryotic CRISPR-Cas adaptive immune systems are revolutionizing genome editing, gene therapy, and disease diagnostics. Recently, several new immune systems have been discovered for which their function remains unknown. The emphasis of this proposal is to determine the structure and function of two newly discovered CRISPR-Cas adaptive immune systems with the primary objectives to (i.) fill gaps in our understanding of these biological systems and (ii) provide the basic mechanistic knowledge necessary to develop these immune systems into new life science tools. To better understand the function of these immune systems we are using cell-based and biochemical assays, as well as structural methods such x-ray crystallography and cryo-EM. We hope to determine how these systems identify their targets, how they distinguish self from non-self, and how their distinct genetic differences (protein domains and genes) impact their function. !