Drugging the human P2X4 receptor - a target in pain and the cardiovascular system (FOUNTAIN_U17DTP)

University of East Anglia - School of Biological Sciences

Start Date: 1st October 2017

No. of positions available: 1

Supervisor: Dr Samuel Fountain

Project description: 
P2X receptors are a family of ligand-gated ion channels activated by extracellular ATP. They are attractive drug targets for the treatment of pain, inflammation and hypertension. Until recently structural information has been lacking for P2X receptors, making it difficult to understand how known drug-like molecules bind to P2X receptors, or predict binding of novel drugs. Recent landmark studies resolved the crystal structure of zebrafish P2X4 in open and closed conformations. These structures reveal that P2X receptors have a molecular architecture distinct from other ion channel protein families. The project will use this structural information to study drug binding at the human P2X4 receptor – a target for novel pain and hypertensive therapies. You will receive training in cutting-edge experimental and computational techniques including molecular modelling, ligand docking to determine the binding pocket of known drug-like molecules, and virtual screening techniques to discover novel ligands. Functional studies will include pharmacological characterisation of molecules by patch-clamp electrophysiology and calcium imaging, receptor mutagenesis and organic synthesis.

You will join an internationally recognise ion channel biology group, and receive training in advanced experimental techniques used in modern drug discovery. The laboratory is well funded with active international collaborations with industrial partners and other academic groups.

Tsuda et al (2003). P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature.

Yamamoto K et al (2006). Impaired flow-dependent control of vascular tone and remodelling in P2X4-deficient mice. Nature Medicine.

Person specification: Minimum entry 2:1

Funding notes: Full Studentships cover a stipend (RCUK rate: £14,296pa – 2016/7), 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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South East England