Droplet-based Microfluidic Platform for Intracellular Ion Channel Drug Discovery

用于细胞内离子通道药物发现的基于液滴的微流控平台

• 批准号: EP/N031849/1
• 负责人: Michele Zagnoni
• 金额: $ 37.98万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN031849%2F1
• 关键词: Droplet; based; Microfluidic; Platform; Intracellular

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.

离子通道是参与几乎所有细胞机制调节的蛋白质，它们构成了第二大药理药物靶点。这些通道的一个家族位于细胞的内腔室（即它们在细胞内），它们通常被排除在工业大通量自动化筛选（例如自动化膜片钳技术）之外，这些筛选只探测外细胞膜中的离子通道。因此，影响这类蛋白质新药的发现率的影响就产生了。本课题旨在生产和测试一种新的微系统技术，用于人体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，本研究将研究两种与癌症和神经变性有关的蛋白质，即CLIC1（用于验证）和CLIC4，目前还没有已知的药理鉴定药物。药物筛选将与工业伙伴阿斯利康和Smartox合作进行。

项目成果

Microdroplet Operations in Polymeric Microtubes.

• DOI: 10.1021/acs.analchem.0c04360
• 发表时间: 2021-02-02
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Zhang Y;Wang Z;New D;Zagnoni M
• 通讯作者: Zagnoni M

A droplet-interface-bilayer platform for the characterization of intra-cellular ion channels

用于表征细胞内离子通道的液滴界面双层平台

• 发表时间: 2018
• 期刊: 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018
• 作者: Zhang Y.

Droplet-based Microfluidic Platform for Intracellular Ion Channel Drug Discovery - EPSRC

用于细胞内离子通道药物发现的基于液滴的微流体平台 - EPSRC

• DOI: 10.21820/23987073.2018.7.68
• 发表时间: 2018
• 期刊: Impact
• 作者: Zagnoni M

Functionalisation of human chloride intracellular ion channels in microfluidic droplet-interface-bilayers

微流体液滴界面双层中人氯细胞内离子通道的功能化

• DOI: 10.1016/j.bios.2019.111920
• 发表时间: 2020
• 期刊: Biosensors and Bioelectronics
• 影响因子: 12.6
• 作者: Zhang Y