Dr P Chen
Prof R S B Williams
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
Most anti epileptic drugs modify synaptic transmission or neuronal excitability and act on ionotropic receptors for the main excitatory (glutamate) or inhibitory (GABA) neurotransmitters or ion channels within the mammalian CNS. 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 glutamate receptors such as NMDA receptors or other ion channels. Furthermore we have little understanding of how DA’s inhibitory activity would influence synaptic network activity within the brain.
We will investigate the action of DA on other ion channels by using recombinant heterologous expression systems such as Xenopus oocytes to express ion channel RNA transcribed in vitro. Furthermore we will use structure-function studies and generate and express mutant channels to identify the amino acid residues contributing to the site of action. We will also try to understand how DA modifies synaptic activity within a neuronal network and we will use patch-clamp electrophysiology in brain slices to investigate the actions of DA.
Please visit our BBSRC DTP webpage to obtain more information on how to apply. Applications are due no later than Tuesday, 15 January 2019. Shortlisted candidates will be notified in early February to schedule an in-person interview during the weeks of 11-22 February, 2019. Any questions about the application process should be sent to [Email Address Removed]. To contact the supervisors see ‘email now’ link below
The BBSRC DTP studentship award will cover the cost of institutional tuition fees for both degrees supplemented by institutional support for those in a Masters programme. The funding also provides an annual tax-free living stipend with at the standard RCUK rate with London weighting. The amount is currently at £16,777pa for the 18/19 Academic Year. Additional funds are provided yearly towards the cost of research, conference attendance, and other relevant training.
Chang P., Augustin K, Boddum K, Williams S, Sun M, Terschak JA, Hardege JD, Chen PE, Walker, M. & Williams, RSB. Seizure control by decanoic acid through direct AMPA receptor inhibition (2016) Brain, 139, pp. 431-443.
Augustin K, Williams S, Cunningham M, Devlin AM, Friedrich M, Jayasekera A, Hussain MA, Holliman D, Mitchell P, Jenkins A, Chen PE, Walker MC, Williams RSB. Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures (2018) Epilepsia, 59:e172-178.
How good is research at Royal Holloway, University of London in Biological Sciences?
FTE Category A staff submitted: 24.00
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