Understanding the Molecular Mechanism of Ion and Amino Acid Transport in Neurons

了解神经元中离子和氨基酸运输的分子机制

• 批准号: 1801228
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 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=studentship-1801228
• 关键词: Understanding; Molecular; Mechanism; Ion; Amino

In neurons, 2 types of transmembrane proteins are required for function: ion channels and transporters. Two-pore domain potassium channels (K2Ps) are a family of membrane proteins involved in the control of neuronal excitability, while transporters of the solute carrier 1 (SLC1) family are involved in amino acid uptake. The 3-dimensional (3D) structures of K2P channel (TREK-2) have recently been solved, providing initial insights into the molecular mechanisms of ion channel function. Much less is known about the function of SLC1 transporters. The aim of this DPhil is to determine the 3D structure of SLC1A transporters by cryo-electron microscopy and to investigate the channel function using identified modulators (e.g. ions or drugs). Similarly, the molecular mechanism of TREK-2 channel will be elucidated using known modulators and X-ray crystallography. The resulting information may be beneficial in the design of pharmacological K2P and SLC1 modulators through medicinal chemistry. Thus, this project will address the Bioscience for Health Doctoral Training Partnerships (DTP) priority area. This project addresses the BBSRC Systems approaches to the biosciences priority, as the biological questions will be answered through integrating data collection with computational modeling. BfH, WCUB, ENWW

在神经元中，功能需要两种类型的跨膜蛋白：离子通道和转运蛋白。双孔结构域钾通道（K2 Ps）是一类参与神经元兴奋性调控的膜蛋白家族，而溶质载体1（SLC 1）家族的转运蛋白则参与氨基酸的摄取。K2 P通道（TREK-2）的三维（3D）结构最近已得到解决，为离子通道功能的分子机制提供了初步见解。对SLC 1转运蛋白的功能知之甚少。本DPhil的目的是通过冷冻电子显微镜确定SLC 1A转运蛋白的3D结构，并使用已识别的调节剂（例如离子或药物）研究通道功能。类似地，将使用已知的调节剂和X射线晶体学来阐明TREK-2通道的分子机制。由此产生的信息可能是有益的药理学K2 P和SLC 1调节剂通过药物化学的设计。因此，该项目将涉及生物科学促进健康博士培训伙伴关系（DTP）的优先领域。该项目解决了BBSRC系统方法的生物科学优先级，生物学问题将通过整合数据收集与计算建模来回答。BfH、WCUB、ENWW