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

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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