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Bravo Group

Bacterial immune systems

Bacteria and parasitic mobile genetic elements (including phage and plasmids) are in an ongoing arms race. This tremendous evolutionary pressure has driven the development of a myriad of sophisticated bacterial defense systems capable of providing immunity. While well-known systems such as CRISPR-Cas have been extensively studied, the rise of metagenome analysis has unveiled a plethora of enigmatic defense mechanisms with unknown mechanisms. These systems must distinguish self from non-self molecules, requiring exquisite specificity to avoid unintended activation and autoimmunity.

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.




Team

Multiple positions are available!
Prospective PhD students or interns: please apply through https://phd.pages.ista.ac.at


Current Projects

Structures of CRISPR-Cas effectors | Mechanisms of bacterial immune systems | Kinetics-guided time-resolved cryo-EM methods development


Publications

Bravo JPK. 2024. Anti-plasmid immunity: A key to pathogen success? Future Microbiology., 1–4. View

Bravo JPK, Ramos DA, Fregoso Ocampo R, Ingram C, Taylor DW. 2024. Plasmid targeting and destruction by the DdmDE bacterial defence system. Nature. 630(8018), 961–967. View

Hibshman GN, Bravo JPK, Hooper MM, Dangerfield TL, Zhang H, Finkelstein IJ, Johnson KA, Taylor DW. 2024. Unraveling the mechanisms of PAMless DNA interrogation by SpRY-Cas9. Nature Communications. 15, 3663. View

View All Publications

ReX-Link: Jack Bravo


Career

Since 2024 Assistant Professor, Institute of Science and Technology Austria (ISTA)
2020 – 2024 Postdoc, University of Texas at Austin, USA
2019 Postdoc, Cambridge University, UK
2015 – 2019 PhD, University of Leeds, Leeds, UK


Selected Distinctions

2023 University of Texas at Austin Department of Molecular Biosciences Outstanding Research Paper Award


Additional Information

Download CV
Bravo Group Website



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