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  Investigation of Campylobacter adhesins and cognate host receptors as potential drug targets


   Faculty of Science, Engineering and Computing

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Prof A Karlyshev  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Background
Campylobacter is the main bacterial cause of gastroenteritis worldwide. In particular, it is the most common cause of diarrhoea in England and Wales with over 50,000 cases of Campylobacter infection reported annually. Despite implementation of various ways to control this pathogen in poultry, chickens remain the most important source of infection in humans. Despite being commensal microorganisms in chickens, C. jejuni cause severe disease in humans. Colonisation of host tissues is an important step in bacterial infection. One of the mechanisms involved in colonisation is attachment of bacteria to host cells via specific interaction between bacterial adhesins and host cell receptors. In addition, adhesins may be involved in biofilm formation protecting bacteria from adverse environmental conditions. So far, few Campylobacter adhesins have been identified and studied. Identification of novel adhesins of Campylobacter and investigation of molecular mechanisms of their interaction of with host cells and abiotic surfaces, as well as in biofilm formation will assist in the development of novel tool to control this pathogen.

Project aims
The main aim of this proposal is the investigation of selected known and putative adhesins using in vitro binding assays. The ultimate aim of the proposed research is a reduction of a number of cases of food poisoning caused C. jejuni via the development of a novel strategy for targeting bacteria both at source of infection (food products) and during infection (in humans).

Methods
A wide range of molecular microbiology techniques will be employed including cloning, PCR, mutagenesis, protein expression and purification, as well as in vitro binding assays. The study will also involve bioinformatics tools to be used for sequence similarity search, amino acid sequence analysis and protein function prediction, as well as for the design of recombinant plasmids for gene expression and mutagenesis.

Requirements to candidates
A candidate must demonstrate strong interest in molecular and/or medical bacteriology, have appropriate training/educational background in relevant areas and satisfy Kingston University entry requirements (upper second class BSc or Master degrees, or equivalent grades). IELTS score of 7.0 or above is required for overseas candidates. Some prior experience and skills in molecular biology/microbiology techniques would be beneficial for successful work on this project. A candidate is expected to be able to produce written reports of publication quality.

Facilities
All facilities and equipment required for work on the project are available at Kingston University in a recently refurbished molecular bacteriology laboratory.

Expertise
The supervisor Prof. A.V.Karlyshev has extensive experience in various areas of microbiology in general, and in Campylobacter studies in particular (70 publications, Nature and other high ranking journals attracting over 300 citations annually).

For further information about this project, please contact
Prof. Andrey V. Karlyshev, [Email Address Removed]

Supervisor profile:

http://sec.kingston.ac.uk/about-SEC/people/academic/view_profile.php?id=80

and

http://staffnet.kingston.ac.uk/~KU40907/

Funding Notes

Suitably qualified candidates (see below) should email the following documents to [Email Address Removed]

- cover letter
- CV
- application form
http://www.kingston.ac.uk/postgraduate/apply-now/documents/ku_postgrad_application_and_reference_form.pdf
- copies of appropriate educational certificates (including IELTS Certificate for overseas applicants)
- two references (should be emailed from the referees directly)

General information about PhD training at KU and entry requirements can be found at
http://www.kingston.ac.uk/research/research-degrees/available-degrees/phd/ and
http://www.kingston.ac.uk/aboutkingstonuniversity/howtheuniversityworks/policiesandregulations/documents/research-degrees.pdf

Annual fees in 2011/12 (check fees using links below):
1) tuition fees: £3,700 and £11,000 for home and overseas students respectively
2) bench fees: £3,000
http://www.kingston.ac.uk/research/research-degrees/fees/

References

1. Champion O.L., Karlyshev A.V., Senior N.J., Woodward M., La Ragione R., Howard S.L.,
Wren B.W., Titball R.W. (2010) Insect infection model for Campylobacter jejuni reveals
that O-methyl phosphoramidate has insecticidal activity. J Infect Dis. 201:776-82.
2. Howard S., Karlyshev A. V., Jagannathan A., Stevens M., Soo E., Logan S. and Wren B.
(2009) Campylobacter jejuni glycosylation island important in cell charge, legionaminic
acid biosynthesis, and colonization of chickens. Infection and Immunity 77:2544-56.
3. Karlyshev A. V., Wren, B. W. and Moran A. P. (2008) Campylobacter jejuni Capsular
Polysaccharide. In: Campylobacter 3rd Edition, Edited by: I. Nachamkin C. M. Szymanski
and M. J. Blaser, pp. 505-521.
4. Karlyshev A. V. and Wren B. W. (2005) Development and application of an insertional
system for gene delivery and expression in Campylobacter. Applied and Environmental
Microbiology 71:4004-13.
5. Karlyshev A. V., Ketley J. M. and Wren B. W. (2005) The Campylobacter glycome. FEMS
Reviews, 29:377-390.
6. Karlyshev A. V., Champion O. L., Szymanski C. M., Churcher C., Brisson J.-R., Jarrell H.
C., Gilbert M., Brochu D., St. Michael F., Goodhead I., Sanders M., Stevens K., White B.,
Parkhill J. and Wren B. W. (2005) Analysis of Campylobacter jejuni capsular loci reveals
multiple mechanisms for the generation of structural diversity and the ability to form
complex heptoses. Molecular Microbiology, 55:90-103.
7. Karlyshev A. V., Everest P., Linton D., Cawthraw P., Newell D. and Wren B. W. (2004)
The Campylobacter jejuni general glycosylation system is important for attachment to
human epithelial cells and in the colonization of chicks. Microbiology 150:1957-64.
8. Karlyshev A. V., Linton D., Gregson N. A. and Wren B. W. (2002) Multiple paralogous
genes of C. jejuni essential for flagella biosynthesis and phase variation. Microbiology,
148:473-480.