Protein-protein interactions in bacterial cell signalling and protein import
In my laboratory we aim to understand how protein-protein interactions (PPIs) in bacteria underpin signalling within the cell envelope and cytoplasm, how changes in the environment modify these interactions to elicit different cellular responses and how such interactions are subverted by antibacterial proteins to catalyse their import into the cell. We study PPIs from a number of bacteria but predominantly from the model Gram-negative organism Escherichia coli. More broadly, we are interested in the molecular mechanisms that underpin specificity and affinity in PPIs, with a particular focus on the association mechanisms of intrinsically disordered proteins. Many of the PPIs we study are important in the virulence mechanisms of pathogens such as Salmonella typhimurium and Pseudomonas aeruginosa and so a long-term goal is the development of small molecules to disrupt these complexes both as a means of probing function in vivo but also to generate leads for novel antibiotics. We adopt a multidisciplinary approach in dissecting biological function that incorporates protein chemistry and engineering, molecular biophysics and structural biology.