Droplet-based Microfluidic Platform for Intracellular Ion Channel Drug Discovery

离子通道是参与几乎所有细胞机制调节的蛋白质，它们构成了第二大类药理学药物靶标。这些通道的家族位于细胞的内室中（即它们是细胞内的），并且它们通常被排除在仅探测外细胞膜中的离子通道的工业大通量自动化筛选（例如自动化膜片钳技术）之外。因此，出现了影响针对此类蛋白质的新药的命中发现率的影响。本研究旨在建立和测试一种新的微系统技术，用于人细胞内离子通道的药物筛选。该系统将包括一个中等通量的微流体原型，完全依赖于含有细胞内离子通道的合成细胞膜。在开发这项新技术的同时，这项研究将研究两种参与癌症和神经变性的蛋白质，即CLIC 1（用于验证）和CLIC 4，目前还没有已知的药理学鉴定药物。药物筛选将与工业合作伙伴阿斯利康和Smartox合作进行。

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.