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Molecular Pharmacology of N-Methyl-D-aspartate glutamate receptors

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Fast neuronal communication at synaptic contacts relies on neurotransmitter release from the presynaptic terminal and the majority of excitatory neurotransmission within the mammalian central nervous system is mediated by the neurotransmitter glutamate. Glutamate acts on a number of ligand gated ion channels often referred to as ’ionotropic’ receptors which when opened permit ion flux across the cell membrane and result in a change in neuronal excitability. One subtype of ionotropic glutamate receptor is the N-methyl-D-aspartate receptor (NMDAR) and these receptors play a number of roles in normal and abnormal processes within the central nervous system (CNS), ranging from learning and memory to excitotoxic neuronal cell death following stroke or brain trauma. The involvement of NMDARs in such a broad range of CNS processes and disorders has triggered a great deal of interest in the molecular determinants of NMDAR function. This knowledge is not only required for teasing apart the complex mechanisms of receptor action but may also assist in the development of therapeutic strategies to combat the neurological damage induced by NMDAR overactivity.

NMDARs are heteromeric protein complexes made up of different types of subunit and my laboratory is interested in understanding how specific regions or ’functional’ domains within these receptor subunits can specify distinct pharmacological or functional properties. We are also interested in exploring the impact of NMDARs with altered pharmacological properties on neuronal function. The laboratory is a using variety of molecular biological, biochemical and functional methods to understand the roles played by these domains in receptor function and pharmacology.


1. 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. * Joint senior author.

2. Semerdjieva, S., Abdul-Razak, H.H., Salim, S.S., Yáñez-Muñoz, R.J., Chen PE., Tarabykin, V. and Alifragis, P. Activation of EphA receptors mediates the recruitment of the adaptor protein Slap, contributing to the downregulation of N-methyl-D-aspartate receptors (2013) Molecular and Cellular Biology, 33, pp.1442-55.

3. Chang, P., Terbach, N., Plant, N., Chen PE., Walker, M.C., and Williams, R.S.B. Seizure control by ketogenic diet-associated medium chain fatty acids (2013) Neuropharmacology, 69, pp. 105-14.
4. Chen PE., Errington, M.L., Kneussel, M., Chen, G., Annala, A.J., Rudhard, Y.H., Rast, G.F., Specht, C.G., Tigaret, C.M., Nassar, M.A., Morris, R.G.M., Bliss, T.V.P., Schoepfer, R. Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus (2009) Learning and Memory, 16 (10), pp. 635-644.

5. Chen PE, Geballe MT, Katz E, Erreger K, Livesey MR, O'Toole KK, Le P, Lee CJ, Snyder JP, Traynelis SF and Wyllie DJ. Modulation of glycine potency in rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes. (2008) Journal of Physiology. 586:227-45.

6. Wrighton DC, Baker EJ, Chen PE and Wyllie DJ. Mg2+ and memantine block of rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes. (2008) Journal of Physiology. 586:211-25.

7. Erreger K, Geballe MT, Kristensen A, Chen PE, Hansen KB, Lee CJ, Yuan H, Le P,Lyuboslavsky PN, Micale N, Jorgensen L, Clausen RP, Wyllie DJ, Snyder JP and Traynelis SF.Subunit-specific agonist activity at NR2A-, NR2B-, NR2C-, and NR2D-containing N-methyl-D-aspartate glutamate receptors. (2007) Molecular Pharmacology. 72:907-20.

8. Chen PE, Geballe MT, Stansfeld PJ, Johnston AR, Yuan H, Jacob AL, Snyder JP, Traynelis SF and Wyllie DJ. Structural features of the glutamate binding site in recombinant NR1/NR2A N-methyl-D-aspartate receptors determined by site-directed mutagenesis and molecular modeling.(2005) Molecular Pharmacology. 67:1470-84.

How good is research at Royal Holloway, University of London in Biological Sciences?

FTE Category A staff submitted: 24.00

Research output data provided by the Research Excellence Framework (REF)

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