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Fully funded 4 year MRC-DTP PhD studentship availible in Manchester , UK

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Institute of Inflammation and Repair | University of Manchester

Project Title: Bacteriophages of Gram positive bacteria: gateways to infection control

Project Supervisor(s):  Dr Guoqing Xia /  Prof J P Derrick  

project duration: September 2015 - August 2019

Funding Availability: Competition Funded PhD Project ( European/UK Students Only)

Application Deadline:  26 November 2014


The rise in antibiotic resistance has prompted a renewed interest in bacteriophage research. A study of the molecular basis for recognition of the bacterial host has applications in detection, vaccine design and control of bacterial infections. Although the role of bacteriophage in bacterial evolution, virulence, clonal diversity is well recognized, the biochemical and structural basis for the interaction of bacteriophages with the cell envelope of Gram positive pathogens is poorly understood. This project will study the molecular mechanisms that mediate cell surface-associated processes such as phage adsorption and phage resistance primarily in Staphylococcus aureus but also in other Gram-positive bacteria, such as coagulase-negative staphylococci. We will use an integrated, multidisciplinary approach involving genetics, biochemistry, structural biology and proteomics.

Specific goals and objectives:

1) We will identify and characterize the staphylococcal cell wall receptors for phages fWS2 by analyzing phage adsorption efficiency using a panel of isogenic cell wall mutants. The cell wall fragments will be isolated, purified and used for inhibition of phage adsorption in order to define the minimum cell wall structures served as phage receptor.

2) Identify the receptor binding proteins (Rbp) of phage fWS2; serum and recombinant Rbps will be generated and immunogold electron microscopy used to localize the Rbp in the bacteriophage tail. The stoichiometry of the Rbps in fWS2 will be determined using a quantitative proteomics approach. The interaction of phage Rbp and its receptor will be analyzed in detail using biochemical and biophysical methods (Pull down assay, Biacore, Fluorescence microscopy/FACS analysis ).

3) The 3D structures of Rbps will be determined by X-ray crystallography and their location in the bacteriophage mapped by cryo-electron microscopy/single particle analysis.

4) Recombinant Rbp will be used to develop agglutination test, a cell capture assay, and capture ELISA as detection methods for S. aureus.

Skills training/methods/techniques:

This studentship is a cross-faculty project, in line with current goals to foster novel collaborations set out by FMHS / FLS.

A) Niche Skills
1. Microbiological, biochemical, biophysical assays
2. Analysis of proteomic data
3. Protein expression and characterisation
4. X-ray crystallography
5. Cryo-electron microscopy and tomography

B) Core and Generic Skills
The full range of skills normally associated with a practical PhD project in the Molecular Biosciences, particularly communication the development of the student as an individual scientist, and ability to design, execute and interpret experiments in a suitable manner
 
This 4-year full-time studentship forms one of our PhD opportunities within the MRC Doctoral Training Partnership (MRC DTP) scheme. Funding provides full support for tuition fees, annual tax-free stipend at Research Council UK rates (currently £13, 863) and conference/travel allowance. The project is due to commence October 2015 and is open to UK/EU nationals only due to the nature of the funding.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in Biochemistry or one of the medical/health sciences. A Masters qualification in a similar area would be an advantage.

Please direct applications in the following format to Dr Guoqing Xia (guoqing.xia@manchester.ac.uk)
  • Academic CV
  • Official academic transcripts
  • Contact details for two suitable referees
  • A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Xia. Applications are invited up to and including 26 November 2014.

Further details on the MRC DTP scheme, shortlisting/interview process and additional PhD project opportunities can be found on our website:

http://www.manchester.ac.uk/research/guoqing.xia/

www.mhs.manchester.ac.uk/mrcdtp
http://www.mhs.manchester.ac.uk/postgraduate/mhs-graduate-school/


References:
1) Winstel V, Liang C, Sanchez-Carballo P, Steglich M, Munar M, Penades JR, Nübel U, Holst O, Dandekar T, Peschel A, Xia G. Wall teichoic acid structure governs horizontal gene transfer between major bacterial pathogens. Nat. Commun, 2013; 4: Article number 2345.

2) Brown S, Xia G*, Luhachack LG, Campbella J, Meredith T, Chen C, Winstel V, Gekeler C, Irazoqui JE, Peschel A, Walker S * Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids. Proc. Natl. Acad. Sci. USA, 2012 Nov 13;109:18909-14. ( * Joint corresponding author; Highlights, commentary in PNAS, recommended by Faculty of 1000)

3) Xia G, Wolz C. Phages of Staphylococcus aureus and their impact on host evolution. Infect Genet Evol. 2014 Jan;21: 593-601.

4) Karuppiah V, Collins RF, Thistlethwaite A, Gao Y, Derrick JP. Structure and assembly of an inner membrane platform for initiation of type IV pilus biogenesis. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):E4638-47.

5) Berry JL, Phelan MM, Collins RF, Adomavicius T, Tønjum T, Frye SA, Bird L, Owens R, Ford RC, Lian LY, Derrick JP. Structure and assembly of a trans-periplasmic channel for type IV pili in Neisseria meningitidis. PLoS Pathog. 2012 Sep;8(9):e1002923
 
 

Kontaktdaten


Art des Bewerbungszugangs
please send you application in one single PDF file by email if  possible
Kontakt für Bewerbungen
Dr Guoqing Xia
email: guoqing.xia@manchester.ac.uk

 

Details der Stellenanzeige


Arbeitszeit
Vollzeit
Vertragslaufzeit
Befristete Anstellung
Stellentyp
Promotionsstelle
Berufserfahrung
Berufserfahrung nicht vorausgesetzt
Region
Großbritannien
Arbeitsort
M13 9PT Stopford Building, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences , The University of Manchester, Oxford Road, Manchester,
Fachgebiet
Biotechnologie, Humanmedizin, Veterinärmedizin, Biologie & Life Sciences, Pharma
JETZT BEWERBEN