Targeting an Achilles heel in bacterial outer membrane biogenesis: Strategies to combat bacterial infection by targeting the periplasmic chaperone SurA

In February 2017 the World Health Organisation published a list of antibiotic-resistant "priority pathogens" – a catalogue of 12 families of bacteria that pose the greatest threat to human health. Of these, 9 are Gram-negative bacteria. In Gram-negative bacteria, the outer membrane (OM) is packed with outer membrane proteins (OMPs), which protect bacteria from potentially damaging molecules such as antibiotics. The biosynthesis of OMPs starts in the cytoplasm and ends with their folding and insertion into the OM. The molecular chaperone SurA escorts these newly made unfolded OMPs through the periplasm to the OM. Not surprisingly, perturbing SurA function leads to a loss of bacterial viability and affects antibiotic resistance, demonstrating that SurA is an attractive target to control Gram-negative pathogens. This project will combine biochemistry, structural biology and in vivo functional characterization to elucidate how SurA activity and chaperone function can be controlled and modulated by small molecules. The outputs of this exiting research project will be to open new avenues to development of novel antibacterial strategies.
We are looking for an enthusiastic and ambitious PhD student with a strong interest in structural biology, biophysics and biochemistry. The successful candidate will be based at the Astbury Centre for Structural Molecular Biology and have access to our world-leading facilities, including NMR, MS and cryoEM.