Analysis of the role and regulation of stress responses and molecular chaperones in bacteria

Projects for excellent students with the relevant background are potentially available in three areas. (a) How acid is detected and how bacteria mount a response to its presence. One project is to look at the EvgS sensor kinase, the main detector of low pH in E. coli, and will map functional domains of this protein using molecular methods to determine how it enables E. coli to respond to external acid stress. We have already selected a number of novel mutants in this protein which will help us to map functional regions and to explore the structural basis for the protein’s role in acid resistance. We also wish to define the EvgS regulon in pathogenic as opposed to lab strains of E. coli. In addition, we are interested in using laboratory-based evolution and whole genome sequencing to explore the ways in which E. coli and other bacteria adapt in the short and long-term to prolonged exposure to low pH. This includes studying the effects of weak organic acids which are found in the gut and are increasingly used as anti-bacterial agents in the treatment of burns (b) Identifying and verifying stress response networks in E. coli. We have an on-going project using RNAseq and TraDIS to map responses of a uropathogenic strain of E. coli to a range of different stresses, with a view to building predictive computational models of the stress networks in E. coli. This overlaps with our interests in looking at how bacteria can evolve to become more able to grow in the presence of mild stresses. The predictions of these models will be tested by constructing relevant mutant strains and investigating their behaviour under different stress conditions (c) The functions and roles of chaperonins in Mycobacteria, with an emphasis on developing model systems in the fish pathogen Mycobacterium marinum. This project will build on our published work on chaperonins in M. tuberculosis and M smegmatis. We have already shown that the non-essential chaperonin of M. tuberculosis is essential for it to form granulomas in experimental animals, and that the chaperonins of Mycobacteria have unusual structures. In this project, we will endeavour to construct deletion mutants of different chaperone genes in the fish pathogen Mycobacterium marinum, with a view to screening these in an animal model for their effects on pathogenicity. We are also interested in the expression and structure of the chaperonins (GroEL homologues) in this organism. All projects in our lab use mainly molecular genetic methods, but we collaborate with several groups who use a range of techniques in biochemistry, biophysics, and systems biology to study the problems we are all interested in.
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Please find additional funding text below. For further funding details, please see the ‘Funding’ section.
The School of Biosciences offers a number of UK Research Council (e.g. BBSRC, NERC) PhD studentships each year. Fully funded research council studentships are normally only available to UK nationals (or EU nationals resident in the UK) but part-funded studentships may be available to EU applicants resident outside of the UK. The deadline for applications for research council studentships is 31 January each year.

Each year we also have a number of fully funded Darwin Trust Scholarships. These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also 31 January each year.