The University of Sheffield Faculty of Medicine, Dentistry & Health Department of Infection and Immunity Probing the mechanism of bacterial toxin-secreting machines and identification of their substrates Supervisors: Mark Thomas and Jon Shaw Project: Many bacterial virulence determinants are secreted proteins (so-called 'effectors' or toxins) that benefit the pathogen by allowing it to subvert or damage the host, or to gain nutrients from the host. In Gram-negative bacteria, secreted proteins are translocated across two membranes by one of at least nine different secretion systems. Therefore, protein secretion systems are essential for the virulence of pathogenic bacteria. A recently discovered bacterial protein secretion machine known as the type VI secretion system (T6SS) plays an important role in the virulence of a variety of pathogenic Gram-negative bacteria. Moreover, in some cases the T6SS also targets other bacteria and therefore plays important role in interbacterial competition. Our work is aimed at building a picture of how the T6SS is organised and elucidating its mechanism of action. In addition, we are also interested in characterising the effectors or toxins that are secreted by this system. For this reason, a variety of projects is available within this theme. Experimental approaches will include a broad range of molecular genetic and biochemical techniques, including DNA cloning, directed mutagenesis, mutant generation, protein overproduction and purification, protein-protein interaction studies, proteomics, protein structure determination. Entry Requirements: Candidates must have a first or upper second class honors degree or significant research experience. Enquiries: Interested candidates should (m.s.thomas@sheffield.ac.uk). How to apply: in the first instance contact Mark Thomas Please complete a University Postgraduate Research Application form and attach at least two references to your application. To complete the application form please visit: www.shef.ac.uk/postgraduate/research/apply. Please clearly state the prospective main supervisor in the respective box and select ‘Infection & Immunity’ as the department. 'The Medical School has received a Silver Athena SWAN award for promoting gender equality’ Website: http://www.sheffield.ac.uk/faculty/medicine-dentistryhealth/graduateschool/prospectivepg/vacancies/ii Closing date: 3rd February 2014