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

神经元的功能需要两种跨膜蛋白：离子通道蛋白和转运蛋白。双孔结构域钾通道（K2Ps）是一个参与控制神经元兴奋性的膜蛋白家族，而溶质载体1 （SLC1）家族的转运蛋白参与氨基酸摄取。K2P通道（TREK-2）的三维（3D）结构最近得到了解决，为离子通道功能的分子机制提供了初步的见解。我们对SLC1转运蛋白的功能知之甚少。本博士的目的是通过低温电子显微镜确定SLC1A转运体的3D结构，并使用确定的调节剂（例如离子或药物）研究通道功能。同样，TREK-2通道的分子机制将利用已知的调制器和x射线晶体学来阐明。所得信息可能有助于通过药物化学方法设计K2P和SLC1的药理调节剂。因此，该项目将处理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系统对生物科学优先级的方法，因为生物学问题将通过将数据收集与计算建模相结合来回答。BfH， WCUB， ENWW

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