PhD Studentship - Mixing It Up: Heteromultimerisation of P2X Receptor and its Impact on Ion Channel Properties and Pharmacology (FOUNTAIN_U18DTP1)

University of East Anglia - Biological Sciences

Start Date: 1st October 2018

No. of positions available: 1

Supervisor: Dr Samuel Fountain

Project description: P2X receptors are ligand-gated ion channels activated by the neurotransmitter extracellular adenosine 5’-triphosphate (ATP). P2X receptors mediate fast biological responses to ATP during the generation of pain responses, development of neuropathic pain and the maintenance of blood pressure. P2X receptors are structurally unusual amongst other ligand-gated ion channel families in that the functional channels are trimeric, formed by the association of three pore-forming subunits. The human genome encodes seven pore-forming subunits (P2X1-7) with all, expect P2X6, capable of forming functional homomers. In rodents, there is clear evidence for the existence of functional heteromeric P2X receptors (formed from different subunits e.g. P2X2/3) but little evidence exists for human P2X receptors. This information is critical for understanding the molecular basis of ATP responses in human tissues, and ensuring the use of useful receptor surrogates during drug development.

This studentship will gain biochemical and functional evidence for the existence of human P2X heteromers, initially exploring heteromerisation of the human P2X4 receptor, a target for pain and blood pressure therapies. The project offers advanced training in patch-clamp electrophysiology, calcium imaging, immunoprecipitation and western blot, mutagenesis and molecular modelling. The project is suited to those interesting in receptor pharmacology and drug discovery.

You will join an international recognised research group based within the Biomedical Research Centre on the Norwich Research Park. The laboratory is very well funded by the British Heart Foundation, BBSRC and industrial partners. We are a highly dynamic group and presentation at domestic and international conferences is encouraged.

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: Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

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 for funding 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