Exploring the effects of decanoic acid on ion channel function and synaptic network activity

We have recently discovered a straight chain ten-carbon fatty acid (decanoic acid, DA) which displays non-competitive antagonism for the AMPA (AMPAR) subtype of glutamate receptor (Chang et al., 2016). Plasma levels of decanoic acid rise in patients prescribed the medium chain triglyceride (MCT) ketogenic diet and have been shown to have antiseizure effects in vitro and in vivo at clinically relevant concentrations. Despite our pharmacological characterization of DA action at AMPARs, there is little information on the molecular basis for DA’s inhibitory activity at AMPARs and the effect of DA on other ion channels. Furthermore we have little understanding of how DA’s inhibitory activity would influence synaptic network activity within the brain.
This project will use heterologous expression systems expressing recombinant proteins to investigate the action of DA on other ion channels and also use structure-function studies and express mutant receptors to identify the amino acid residues contributing to the site of action (Chen and Williams). It will also try to understand how DA modifies synaptic activity within a neuronal network and we will use patch-clamp electrophysiology in slices (Brickley) to investigate the actions of DA.

This PhD project will be supervised jointly by:
1. Dr Philip Chen, Department of Biological Sciences, Royal Holloway University of London
2. Prof Stephen Brickley, Department of Life Sciences, Imperial College London

Applicants are invited to contact supervisor(s) by email ahead of submitting their application. Further information about applying for a postgraduate course at Royal Holloway can be found here:
https://www.royalholloway.ac.uk/studying-here/applying/postgraduate/how-to-apply/

Applications should be submitted online:
https://admissions.royalholloway.ac.uk/#/HEapplicationForm////////1