PhD Studentship - How Bacterial Pathogens "Sweeten" Host Proteins to Avoid Immunological Responses: Structural Study of Sugar Transfer by Bacterial Virulence Factors (ANGULO_U18DTP)

University of East Anglia - Pharmacy

Location: Norwich

Start Date: 1 October 2018

No. of positions available: 1

Supervisor: Dr Jesus Angulo

Project description: Antimicrobial resistance is one of the biggest threats to global health. To reduce it, we must ensure that antibiotics are used only where appropriate. Accordingly, other non-antibiotic approaches are welcome, and a better understanding of the biology of bacterial infections is required. Pathogens such as Salmonella and E. coli inject virulence factors (effectors) to suppress antimicrobial host responses, to promote colonisation. The NleB effector is highly conserved among pathogens. It transfers GlcNAc sugar residues to host proteins (GAPDH, FADD, TRADD), a "sweet tag” that inhibits NF-kB activation and apoptosis of infected cells, blocking major antimicrobial host responses.

In this project, we will use advanced NMR spectroscopy, molecular modelling (protein-ligand docking, long molecular dynamics simulations), and other biophysical techniques (ITC) to unveil the structural features at atomic detail of the molecular recognition of host proteins by the bacterial effectors NleB1, SseK1, and SseK2. Members of this conserved family modify different host proteins and exhibit distinct modes of action to suppress host responses, but, interestingly, they differ only in a very small number of amino acids. We will try to rationalise the molecular basis of their exquisite selectivity, and the impact of sugar transfer on the interactions with other host proteins such as TRAF2.

The project is an excellent opportunity for first class student training in a multidisciplinary environment. The student will be trained in advanced NMR spectroscopy, modelling, recombinant protein production, and Isothermal Titration Calorimetry. UEA and NRP also provide training in research techniques, data handling, and transferable skills in paper and grant writing and presentation skills.

This project has been shortlisted for funding by the Norwich Biosciences Doctoral Training Partnership (NRPDTP). Shortlisted applicants will be interviewed as part of the studentship competition.

Candidates will be interviewed on either the 9th, 10th or 11th January 2018.

The Norwich Biosciences Doctoral Training Partnership (NRPDTP) offers postgraduates the opportunity to undertake a 4 year research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three month professional internship (PIPS) during their study. The internship offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. For further information and to apply, please visit our website: www.biodtp.norwichresearchpark.ac.uk

Person specification: Standard minimum entry requirements: 2:1 or equivalent.

Funding notes:

Full Studentships cover a stipend (RCUK rate: £14,553pa – 2017/8), research costs and tuition fees at UK/EU rate, and are available to UK and EU students who meet the UK residency requirements.
Students from EU countries who do not meet the UK residency requirements may be eligible for a fees-only award. Students in receipt of a fees-only award will be eligible for a maintenance stipend awarded by the NRPDTP Bioscience Doctoral Scholarships, which when combined will equal a full studentship. To be eligible students must meet the EU residency requirements. Details on eligibility forfunding on the BBSRC website: www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf

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Type / Role:

PhD

Location(s):

South East England