BBSRC-DTP PhD Studentship (Fixed Term)

University of Cambridge - Department of Pharmacology

PhD studentship: Rational development of novel small molecule leads against the transcriptional activator protein ExsA of Pseudomonas aeruginosa

A 4-year BBSRC-funded DTP studentship starting in October 2017 is available to work on a collaborative project between the research groups of Dr Taufiq Rahman (Department of Pharmacology) and Dr Martin Welch (Department of Biochemistry).

Pseudomonas aeruginosa is a frequent cause of nosocomial infections, including those involving the lungs, the urinary tract, wounds, burns, cornea and the bloodstream. The primary virulence determinant for these acute infections is the type III secretion system (T3SS) which serves effectively as a molecular syringe that directly injects effector proteins into the host cells. This project aims at suppressing T3SS expression by chemically targeting the transcription factor ExsA which is the master regulator of all the genes that encode proteins constituting and regulating the T3SS. It will involve in silico screening of large chemical libraries to find novel chemotypes as preliminary hits against ExsA, the latter will be purified and the top-ranked hits will be characterised through various biophysical and biochemical as well as cell based assays for their ability to a) bind to the ExsA b) to suppress T3SS expression and c) to attenuate virulence of P.aeruginosa. With the most promising molecules, a preliminary structure-activity relationship (SAR) as well as any possible intrinsic toxicity towards eukaryotic cells will also be assessed.

Applicants should have (or expect to obtain) the equivalent of a UK first class or upper second-class honours degree in a relevant discipline in the natural sciences (e.g. chemistry, pharmacology, biochemistry, bioinformatics). We particularly welcome applications from students interested in working at the interface between biology and chemistry. Some background in protein purifications/biochemical techniques with/without in silico screening will be advantageous.

We are looking for a highly motivated, enthusiastic individual, capable of thinking and working independently.

Eligibility and funding for this studentship are in accordance with the Cambridge BBSRC-DTP scheme, details available here: http://bbsrcdtp.lifesci.cam.ac.uk/dtpprog. Any enquiries should be addressed to Dr Taufiq Rahman (mtur2@cam.ac.uk) or Dr Martin Welch (mw240@cam.ac.uk).

To apply, please e-mail the following to pharsect@hermes.cam.ac.uk:

  • your CV with full contact details of 2 academic referees (max two A4 pages)
  • your academic transcript
  • a cover letter (max two A4 pages) highlighting your background/research interests and how these fit to the proposed project

Deadline for application: December 20, 2016

Interviews will take place between 24th and 31st January 2017.

Please quote reference PL10825 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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Type / Role:

PhD

Location(s):

South East England