Bravo Group

Bacterial immune systems

Bacteria are major causative agents of disease in humans. In addition, bacteria are under immense evolutionary pressure from their viral predators—bacteriophages—and have consequently developed numerous sophisticated immune systems to provide immunity. Recent technical breakthroughs have led to the discovery of over 200 previously undetected bacterial immune systems involved in anti-phage defense, antibiotic resistance, and bacterial pathogenesis. Notably, these novel systems represent an untapped treasure trove of tools for precision biotechnology, akin to CRISPR.

The Bravo group is particularly interested in understanding how diverse bacterial immune systems can identify self from non-self nucleic acids, and the consequences of activation. We use a combination of structural biology (typically cryo-electron microscopy), biochemistry, biophysics and functional assays to understand the molecular mechanisms that underpin immunity. Our emphasis on cryo-electron microscopy and pre-steady state kinetic analysis enables the visualization of transient intermediate conformational states, providing insights into the active enzymes’ dynamic and heterogeneous nature.

Our ultimate goal is not only understanding these systems but harnessing that knowledge for rational structure-based engineering. Through this approach, we aim to redesign these defense systems, tailoring them to possess specific, desirable properties. These engineered systems typically exhibit enhanced efficiency and specificity, transforming into potent tools for genome editing and diagnostics. By tapping into the diverse enzymatic activities of newly discovered defense systems, we aspire to unveil a new arsenal of precision tools for molecular biology, poised to shape the future of biotechnological advancements.