Structure-function studies of bacterial cell envelope machines involved in pathogenesis

The bacterial cell envelope comprises the cell wall and either one or two membranes. The cell envelope is of major interest in infection biology because it is the site at which pathogenic bacteria interact with their host organism. In particular, bacterial virulence proteins must be transported across the cell envelope to affect the host.

We aim to understand the molecular mechanisms by which proteins, nucleic acids, and mechanical force are transferred across and along the cell envelope in processes of biomedical importance. The project is to undertake structure-led studies of  the dedicated nanomachines that carry out these processes. The NCI part of the collaboration will involve structural analysis, primarily by cryoEM. The Oxford part of the collaboration will concentrate on complementary mechanistic work using biochemical, genetic, and live cell single molecule imaging methods. Our groups  have collaborated for more than 15 years on projects including the transport of folded proteins across the bacterial inner and outer membranes (Tat protein transport system and Type 9 Secretion System), lipoprotein export, DNA transport during horizontal gene transfer (conjugation and natural competence), and gliding motility.