Biophysical and molecular characterisation of ORAI channel properties in skin-derived human cell lines

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The mechanism of store operated calcium entry (SOCE) in non-excitable tissues was first shown to be facilitated by the proteins STIM and Orai in 2006. This mechanism is now known to be key to controlling a variety of functions in a wide range of tissues, and especially for its role in regulating the immune and central nervous systems. More recently, STIM and Orai have been shown to mediate intracellular Ca2+ signalling in skin keratinocytes and cells from a variety of skin appendages. The objective of this proposal is to use a multi-disciplinary approach to characterise the biophysical and molecular behaviour of Orai channel isoforms expressed in a selection of skin-derived cell lines. Methodologies will include cell culture, patch clamp electrophysiology, and bioinformatics / computational biology. The work will occur at three sites: the Institute of Integrative Biology, University of Liverpool, the Hartree Centre, STFC Daresbury, and Unilever Research & Development, Port Sunlight. The objective of the project is to provide the first detailed biophysical characterisation of the kinetic behaviour and modulatory potential of the Orai channel in the context of skin cell behaviour. The project will allow the student to:1. Derive their own biological questions, and explore these both experimentally and via state-of-the art in silico computer modelling2. Master cutting-edge patch clamp electrophysiology techniques for measuring specific ion channel activities3. Understand the nature of academic:industrial collaborations and industrially-relevant research questions