We take a multi-disciplinary approach to understanding bacterial protein transport
We study the molecular machines involved in forming the bacteria cell envelope, with a special emphasis on those machines that transport macromolecules across the cell membranes. These nanomachines have crucial roles in pathogenesis, motility, and antibiotic resistance, and are amongst the most mechanistically interesting proteins in the cell. The most established systems under study in our laboratory are:
The Tat (twin-arginine translocation) protein transport system which exports folded proteins across the bacterial inner membrane. The Tat system is involved in a wide range of fundamental cellular processes in bacteria and is essential for the virulence of bacterial pathogens. The mechanism of Tat transport is radically different from that employed by other protein transporters, enabling it to translocate folded proteins without compromising the ion permeability barrier of the membrane.
The Type IX secretion system (T9SS) which is involved in severe dental disease and in bacterial gliding motility. This multi-component system exports proteins through a huge pore in the outer membrane using the energy of the inner membrane proton electrochemical gradient.
Our work is grounded in protein biochemistry and bacterial cell biology to which we add a full range of cutting edge molecular techniques. In particular, we collaborate with local colleagues on the structural analysis of the transporter complexes by cryoEM, X-ray crystallography, and other approaches, and we dissect the transport processes using live cell single molecule fluorescence imaging.