Investigating electroneutral cation-Cl- cotransporters activity in neurological disorders. Medical Sciences PhD (Self Funded)

Location: University of Exeter, Streatham Campus, Exeter EX4 4QJ

Project description:
The electroneutral cation-Cl- cotransporters (CCCs) are secondary-active plasmalemmal ion transporters that utilize electrochemically favorable trans-membrane gradients of Na+ and/or K+, established by primary active transport via the ouabain-sensitive Na+, K+-ATPase, to drive the transport of Cl- (and K+) into or out of cells. The two CCC subtypes include the Cl--importing, Na+-driven CCCs, such as NKCC1 and the Cl--exporting, K+-driven CCCs (KCC1-4). These evolutionarily conserved transporters are among the most important mediators of ion transport in multicellular organisms, with particular importance in mammalian CNS regulation of ionic and water homeostasis.

This studentship will investigate i) the role of CCCs in the regulation of intracellular chloride concentration within postsynaptic neurons, ii) on the consequent effects on the actions of the neurotransmitter gamma-aminobutyric acid (GABA) mediated by GABAA receptors (GABAARs) during development and in pathophysiological conditions such as epilepsy, and iii) the therapeutic modulation of neurological disorders by targeting of the upstream kinase signalling of CCCs, such as WNKs-SPAK/OSR1, via enhancing cellular chloride extrusion. This project will provide training expertise in the state of the art biochemistry, molecular biology, cell signalling, mass spectrometry, electrophysiology, data analysis as well as generic (statistics, communication, written and oral presentation).


For more information about the project and informal enquiries, please contact the primary supervisor Dr Jinwei Zhang: [Email Address Removed]