PhD Research Project: Mechanisms of Gram-negative bacterial infection and development of protective

The ability of Gram-negative bacteria to adhere to, invade and survive in the host is critical to their ability to cause disease. Understanding the components bacteria use for these processes is essential for understanding the mechanism of disease and for vaccine development.

Our group has a specific interest in the pathogenesis of Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa and Klebsiella pneumoniae. These organisms are important because of their disease burden, their increasing resistance to antibiotics and the lack of an effective vaccine.

This research project will be student lead. The student will use reverse vaccinology approaches to identify antigens that may be involved in pathogenesis. Subsequently, they will examine the ability of wild-type bacteria and mutant derivatives to cause infection in model organisms and in in vitro assays. In addition, the researcher will investigate the protective effect of these antigens in challenge models to establish if they can be used to protect against infection.

Techniques may include imaging of mammalian cells during infection by confocal microscopy, immunofluorescence and electron microscopy; mutation of bacterial genes encoding secreted proteins; use of reporter constructs to localize bacteria within the host, and investigation of virulence gene expression.

This project is appropriate for someone interested in vaccinology or applying molecular biology and cell imaging techniques to the study of microbial pathogenesis.

At the University of Birmingham, Institute of Microbiology and Infection, you will be part of a vibrant and lively postgraduate community and one of the world-leading institutes for microbiological and infectious disease research.

Person Specification
If you are an enthusiastic scientist with an interest in host-pathogen interactions, looking for a PhD position, we would be happy to hear from you. A background in immunology, microbiology or molecular genetics would be helpful. An enthusiastic approach to science, together with the ability to take ownership of your own project within a young, dynamic research team, is essential. You should have a commitment to academic research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.

How to apply
Informal enquiries should be directed to Prof. Ian Henderson
Applications should be directed to Ian Henderson (email i.r.henderson@bham.ac.uk). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
• All applicants should indicate in their applications how they intend to fund their studies.

Funding notes:
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 Institute of Microbiology and Infection offers a number of UK Research Council (http://www2.warwick.ac.uk/fac/cross_fac/mibtp/; http://www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/mrc-impact/index.aspx) PhD studentships each year and studentships funded by Wellcome (http://www.birmingham.ac.uk/schools/mds-graduate-school/wellcome-aamr/index.aspx; http://www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/wellcome.aspx). 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 and Wellcome studentships is in January each year.

Each year we also have a number of fully funded Darwin Trust Scholarships (http://www.birmingham.ac.uk/postgraduate/funding/darwin-studentships.aspx). 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 in January each year.

Please note the only funding available for this PhD is via the Scholarships mentioned.

Funding Notes

Please see three funding options above in the project description.

References

Timothy J. Wells, John Davison, Emma Sheehan, Suren Kanagasundaram, Calman A. MacLennan, Robert A. Stockley, Adam F. Cunningham, Ian R. Henderson, Anthony De Soyza. The use of plasmapheresis in patients with bronchiectasis with Pseudomonas infection and inhibitory antibodies. AJRCCM. 2017.

Timothy J. Wells, Deborah Whitters, Yanina R. Sevastsyanovich, Jennifer N. Heath, John Pravin, Margaret Goodall, Douglas F. Browning, Matthew K. O’Shea, Amy Cranston, Anthony De Soyza, Adam F. Cunningham, Calman A. MacLennan, Ian R. Henderson, Robert A. Stockley. Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing. J Exp Med. 2014 211: 1893–1904.

Calman A. MacLennan, James J. Gilchrist, Melita A. Gordon, Adam F. Cunningham, Mark Cobbold, Margaret Goodall, Robert A. Kingsley, Joep J. G. van Oosterhout, Chisomo L. Msefula, Wilson L. Mandala, Denisse L. Leyton, Jennifer L. Marshall, Esther N. Gondwe, Saeeda Bobat, Constantino López-Macías, Rainer Doffinger, Ian R. Henderson, Eduard E. Zijlstra, Gordon Dougan, Mark T. Drayson, Ian C. M. MacLennan, Malcolm E. Molyneux. Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults. Science. 2010 328: 508–512.