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

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

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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To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in each school, the funding opportunities for each subject, and guidance on making your application, you can now order your copy of the new Doctoral Research Prospectus, at: http://www.birmingham.ac.uk/students/drp.aspx
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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.

Funding Notes

All applicants should indicate in their applications how they intend to fund their studies. We have a thriving community of international PhD students and encourage applications at any time from students able to find their own funding or who wish to apply for their own funding (e.g. Commonwealth Scholarship, Islamic Development Bank).

The postgraduate funding database provides further information on funding opportunities available View Website and further information is also available on the School of Biosciences website View Website

References

Lund PA, Tramonti A, de Biase D. Coping with low pH: molecular strategies in neutralophilic bacteria. FEMS Micro Rev in press (2014)

Johnson MD, Bell J, Clarke K, Chandler R, Pathak P, Xia Y, Marshall RL, Weinstock GM, Loman NJ, Winn PJ, Lund PA. Characterization of mutations in the PAS domain of the EvgS sensor kinase selected by laboratory evolution for acid resistance in Escherichia coli. Mol Microbiol 93: 911-27 (2014)

Hu Y, Coates AR, Liu A, Lund PA, Henderson B. Identification of the monocyte activating motif in Mycobacterium tuberculosis chaperonin 60.1. Tuberculosis (Edinb) 93: 442-7 (2013)

Browning DF, Wells TJ, França FL, Morris FC, Sevastsyanovich YR, Bryant JA, Johnson MD, Lund PA, Cunningham AF, Hobman JL, May RC, Webber MA, Henderson IR. Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis. Mol Microbiol 87: 939-50 (2013)

Parnas A, Nisemblat S, Weiss C, Levy-Rimler G, Pri-Or A, Zor T, Lund PA, Bross P, Azem A. Identification of elements that dictate the specificity of mitochondrial Hsp60 for its co-chaperonin. PLoS One. 2012 7: e50318 (2012)

Batt SM, Jabeen T, Bhowruth V, Quill L, Lund PA, Eggeling L, Alderwick LJ, Fütterer K, Besra GS. Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors. Proc Natl Acad Sci USA 109:11354-9 (2012)

Fan MQ, Rao T, Zacco E, Ahmed MT, Shukla A, Ojha A, Freeke J, Robinson CV, Benesch JL, Lund PA. The unusual mycobacterial chaperonins: evidence for in vivo oligomerisation and specialisation of function. Mol Microbiol 85: 934-44 (2012)

Stincone A, Daudi N, Rahman AS, Antczak P, Henderson IR, Cole JA, Lund PA, Falciani F. A systems biology approach sheds new light on Escherichia coli acid resistance. Nucleic Acids Res 39: 7512-28 (2011)

Johnson MD, Burton NA, Gutiérrez B, Painter K, Lund PA. RcsB is required for inducible acid resistance in Escherichia coli and acts at gadE-dependent and -independent promoters. J Bacteriol 193: 3653-6 (2011)

Rao T, Lund PA. Differential expression of the multiple chaperonins of Mycobacterium smegmatis. FEMS Micro Lett 310: 24-31. (2010)

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