Function of P2X7 in healthy and diseased skin

P2X7 is a purinergic receptor that responds to high extracellular ATP concentrations by opening a fast ligand-gated cation channel or, on prolonged stimulation, by opening a pore permeable to large organic cations, which can initiate cellular apoptosis. High extracellular ATP concentrations occur upon injury and in the cancer microenvironment. Biosceptre has identified a novel form of P2X7, lacking pore function that is specifically expressed in many cancers and acts as a calcium channel promoting cell survival and driving metastasis.

This novel form of P2X7 represents an attractive target for therapeutic intervention and Biosceptre has developed antibodies specific to P2X7 which form the basis of a topical therapeutic that has shown indications of efficacy in treating squamous (SCC) and basal (BCC) cell carcinoma of the skin.

The project will use a spectrum of cell signalling and pharmacological technologies to explore P2X7 function in normal and SCC keratinocytes. These will include siRNA and antibody mediated blockade of downstream signalling function in sophisticated 3D model systems and will place particular emphasis on apoptotic pathways and how these can be exploited as a therapeutic strategy to treat skin cancer.

This project is in partnership with Biosceptre (http://www.biosceptre.com/) located on the Babraham Research Campus in Cambridge and Sydney, Australia and incorporates an industrial training placement. This project has the potential to make significant contributions to this exciting and emerging field examining the role of P2X7 in normal and diseased tissue and its potential as a therapeutic target in cancer. We are therefore seeking a highly motivated graduate student with an interest in cell biology and cancer therapeutics to join our group