P2X receptors (P2XR) are a family of ligand-gated ion channels. P2XRs are activated upon binding of extracellular ATP and allow the influx of small cations after channel opening. The human genome encodes seven P2XR paralogs (P2XR1-P2XR7) that have distinct roles and show tissue specific expression raising their therapeutic potential. Structurally, P2XRs are characterised by a large extracellular ligand binding domain, two transmembrane helices, and intracellular N- and C-termini. Key questions for receptor function are how ATP triggers the opening of the channel, how the receptor transits back from the open to the closed state via a desensitized state, and how small molecule antagonists affect receptor function. We will use computational techniques such as homology modelling, molecular dynamics simulations and evolutionary analysis to understand the mechanistic details of the transitions between these states and to inform drug design.
Academic entry requirements: UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.