Delivery and misdelivery of outer membrane proteins to the BAM complex using cryoEM

Summary

The BAM complex folds membrane proteins into the outer membrane of Gram-negative bacteria, proteins whose functions are essential for bacterial viability, pathogenicity and virulence. Targeting OMP biogenesis is thus a potential route to combat antibiotic resistance. In recent work we have solved high-resolution cryoEM structures of BAM bound to antibacterial antibody fragments (White et al, Nat. Commun. (2021)). In this PhD studentship we will use state of the art cryoEM and protein engineering to solve the 3D structures of complexes between BAM and the chaperone and protease molecules that are essential for its function in vivo.

You will get extensive hands-on experience with state-of-the-art cryoEM infrastructure at the Astbury Biostructure Laboratory, learning to solve the 3D structures of membrane proteins to near atomic resolution, and use molecular biology, and biophysical techniques to test complex formation, and folding activity the BAM complex.

The outcome will be new fundamental knowledge of how OMPs are folded and how toxicity from OMP misfolding is dealt with, knowledge with broad benefits and potential applications in microbiology and antimicrobial resistance.

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