Droplet-based Microfluidic Platform for Intracellular Ion Channel Drug Discovery

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Ion channels are proteins that are involved in the regulation of almost every cellular mechanism and they constitute the second largest class of pharmacological drug targets. A family of these channels are located in the inner compartments of a cell (i.e. they are intracellular) and they are typically excluded from industrial large-throughput automated screening (e.g. automated patch clamp technology) that probe ion channels only in the outer cell membrane. As such, implications arise that affect the hit discovery rate of new drugs for such proteins. This proposal aims to produce and test a new microsystem technology for drug screening of human intracellular ion channels. The system will comprise a medium-throughput microfluidic prototype relying entirely on synthetic cell membranes harbouring intracellular ion channels. Whilst developing this new technology, this study will investigate two proteins that are involved in cancer and neurodegeneration, namely CLIC1 (used for validation) and CLIC4, which currently has no known pharmacological identified drug. Drug screening will be done in collaboration with industrial partners AstraZeneca and Smartox.