Type IV pili machineries are bacterial molecular nanomachines that perform the dynamic assembly and disassembly of type IV pili, filamentous helical protein structures. They are present in a broad range of bacteria including human pathogens making them potential drug targets. Although most of the components are now known, how these molecular machines function is still unclear. They are composed of about 15 proteins located in the inner and outer membrane of bacteria which constitute the moving parts of these machines. We are combining different approaches to better understand how type IV pili machinery function using mass spectrometry-based in situ cross-linking (Rey, Anal Chem, 2021), single particle cryo-EM and Cryo-Electron Tomography. Availability of small molecule inhibitors also provide unique tools to understand how these structures work (Aubey et al, PNAS, 2019) by blocking machineries at specific steps of the assembly sequence.
This project will be hosted and funded by the Pathogenesis of Vascular infections Unit (Head: Guillaume Duménil) at Institut Pasteur (Paris, France). The candidate will be integrated in an interdisciplinary team that combines biochemistry, microbiology, cell biology, biophysics and animal models of infection. This project will take advantage of the vivid scientific environment of the campus and the numerous available core facilities available including the presence of TFS Aquilos, Glacios and Titan Krios microscopes for CryoEM and CryoET.
We are looking for a motivated young scientist with MSc or PhD in structural biology, biochemistry or related disciplines. Some experience in protein purification, sample characterization and in cryo-EM/cryo-ET data acquisition/processing is expected. Basic programming skills is recommended. The candidate should feel comfortable with interdisciplinary science including biophysics, microbiology, immunology and engineering. Excellent communicational and presentational skills in English is expected.