PhD Research Project: What is the molecular basis for protein secretion in Gram-negative bacteria?

Protein secretion machines are the instruments of microbial warfare! Using these machines bacteria produce adhesins, toxins, enzymes and mediators of motility. These proteins are either secreted to or beyond the bacterial cell surface. These secreted proteins may interact directly with host cells resulting in disease. The simplest and most widely utilised secretion systems fall under the rubric of Type 5 secretion systems (T5SS). This category comprises those proteins secreted by the classical Autotransporter system, the two-partner system and the trimeric Autotransporter system. The importance of proteins secreted via the T5SS is illustrated by the fact that in some cases they form part of current human vaccines; thus filamentous haemagglutinin and pertactin are essential components of the acellular whooping cough vaccine. Furthermore, Autotransporters are often essential virulence factors and in the case of Shigella, the agent of bacillary dysentery, abolition of the gene encoding the Autotransporter IcsA results in an attenuated strain which forms the basis for a live attenuated Shigella vaccine. Thus, further understanding of these proteins may lead to greater healthcare benefits.

The objectives of the project can be shaped by the interests of the student but can include investigating the mechanisms of gene regulation, the molecular mechanisms of biogenesis, interaction of proteins with host cells and exploiting the system for commercial protein production. The project will train the student in the use of bioinformatics, molecular genetics and protein biochemistry.
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 available in the project description above.

References

Leyton DL, Rossiter AE, Henderson IR. From self sufficiency to dependence: mechanisms and factors important for autotransporter biogenesis. Nat Rev Microbiol. 2012 Feb 16;10(3):213-25

Sevastsyanovich YR, Leyton DL, Wells TJ, Wardius CA, Tveen-Jensen K, Morris FC, Knowles TJ, Cunningham AF, Cole JA, Henderson IR. A generalised module for the selective extracellular accumulation of recombinant proteins. Microb Cell Fact. 2012 11:69.

Leyton DL, Sevastsyanovich YR, Browning DF, Rossiter AE, Wells TJ, Fitzpatrick RE, Overduin M, Cunningham AF, Henderson IR. Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins. J Biol Chem. 2011 Dec 9;286(49):42283-91