Pathogenesis and Prevention of Bacterial Meningitis
The group is interested in defining the mechanisms by important bacterial pathogens to cause disease in their human host, and applying these finding to the development of vaccines and therapeutics.
Shigella spp. are a leading cause of dysentery world-wide and estimated to be responsible for around 900,000 deaths each year, particularly among children in resource poor settings. The bacterium can enter non-phagocytic cells through the activity of its Type Three Secretion System (TTSS). It is also one of the few bacterial pathogen that can enter into and replicate within the cytosol of human cells. The group are interested in understanding the function of the TTSS, and how its activity are regulated by environmental signals. We have also initiated research into bacterial replication and survival within different cell types, at the single bacterial and cell level. The group collaborates with Philippe Sansonetti (Institut Pasteur) and Professor Susan Lea (Sir William Dunn School).
Work on Neisseria meningitidis focuses on the ability of bacteria colonise the nasopharynx (its normal habitat) and avoid immune killing. The bacterium expresses Type IV pili (Tfp) which are required for adhesion to epithelial cells, and antigenic variation in pilin, the major constituent of Tfp, is a paradigm for immune evasion in pathogens. However we have found that strains that cause epidemic disease actually express a highly conserved pilin, and we are studying how this is achieved by successful disease-causing lineages of the meningococcus. The bacterium has several mechanisms to evade complement mediated killing, including producing a polysaccharide capsule and fHbp which binds the negative complement regulator, factor H. We are investigating these and other molecules which contribute to meningococcal virulence. Additionally our studies on DNA repair have revealed novel specialisation in the Base Excision Repair pathway.
Click here for details of project available through 4 year DPhil Departmental Studentship Competition 2013