Function and pharmacology of the human P2X4 receptor for ATP (FOUNTAINU16SF)
P2X receptors (P2X1-7) are a family of cell surface ligand-gated ion channels activated by extracellular adenosine 5’triphosphate (ATP) associated with painful and inflammatory signalling. Functional P2X receptors assembly as homo- and hetero-trimers, though the composition of human P2X4 subunit containing receptors has not been fully explored. P2X4 activity is associated with the development of neuropathetic pain and the relaxation of arteries, but the composition and stoichiometry of human P2X4-containing receptors is unclear. The overarching aim of this project is to explore the molecular and functional evidence for association of the human P2X4 subunit with other P2X subunit family members, exploring the impact on ion channel properties and pharmacology in recombinant and native systems such as macrophage. These are important considerations for future drug development.
The project will involve training in a number of cutting-edge cellular and molecular techniques to explore P2X4 function, specifically dynamic intracellular calcium measurements, patch-clamp electrophysiology, production and use of viruses for gene expression and knockout, protein chemistry and confocal microscopy. We are a lively, internationally recognised and well-funded research team funded by the BBSRC and British Heart Foundation. The laboratory is situated in the state-of-the-art Biomedical Research Centre.
This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://www.uea.ac.uk/pgresearch/pgrfees.
A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.
i) Li J, Fountain SJ (2012). Fluvastatin suppresses native and recombinant human P2X4 receptor activity. Purinergic Signal. 8: 311-6.
ii) Young MT, Fisher JA, Fountain SJ, Ford RC, North RA, Khakh BS (2008). Molecular shape, architecture and size of P2X4 receptors determined using fluorescence resonance energy transfer and electron microscopy. Journal of Biological Chemistry 283:26241-26251.
iii) Fountain SJ, North RA (2006). A C-terminal lysine that controls human P2X4 receptor desensitization. Journal of Biological Chemistry 22: 15044 – 15049.