Professor David E Jane

B.A.(Cantab.), Ph.D.(Salf.), M.R.S.C.

  • BS8 1TD

1993 …2020

Research output per year

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Personal profile

Research interests

Glutamate receptors are the major excitatory synaptic receptors in brain and spinal cord. They are of two major types, ionotropic and metabotropic glutamate receptors.

Ionotropic glutamate receptors (iGluRs), which mediate fast synaptic responses via ion fluxes, are further subdivided into three main groups characterised by their preferential agonists N-methyl-D-aspartate (NMDA), kainate and (S)-a-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA). The work of the group combines chemistry and pharmacology. We have synthesized and pharmacologically characterised a range of selective agonists and/or antagonists for each of these receptors by means of which the synaptic receptors in various brain and spinal cord pathways can be identified.

The work of the group can be split into three key areas:

  • Design of novel glutamate receptor agonists and antagonists. The group has recently acquired state of the art computer-aided molecular modelling facilities to take advantage of the recently published X-ray crystal structures of glutamate receptor ligand binding cores.
  • Chemical synthesis of target amino acids. The group is based in a recently refurbished chemistry laboratory and has access to all the facilities of the adjacent School of Chemistry. The chemistry undertaken by the group is very varied and includes the synthesis of heterocyclic compounds and the synthesis of novel analogues of natural products. As the target amino acids are usually chiral a number of techniques are used to obtain separate enantiomers including asymmetric synthesis and resolution by crystallisation of diastereoisomers and by chiral HPLC. 
  • Pharmacological characterisation of novel compounds. Assays using cloned mGlu and iGlu receptors subtypes are currently used to characterise compounds synthesised by chemists within the group.  In collaboration with other groups in Bristol (e.g. Graham Collingridge and Elek Molnar) and elsewhere the pharmacological tools we have developed are used to understand the physiological roles of individual glutamate receptor subtypes.

 

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Projects

Research Output

Structural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors

Wang, J. X., Irvine, M. W., Burnell, E. S., Sapkota, K., Thatcher, R. J., Li, M., Simorowski, N., Volianskis, A., Collingridge, G. L., Monaghan, D. T., Jane, D. E. & Furukawa, H., 22 Jan 2020, In : Nature Communications. 11, 1, 14 p., 423.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
File
  • 1 Citation (Scopus)
    52 Downloads (Pure)

    Assembly and Trafficking of Homomeric and Heteromeric Kainate Receptors with Impaired Ligand Binding Sites

    Scholefield, C., Atlason, P., Jane, D. & Molnar, E., 1 Mar 2019, In : Neurochemical Research. 44, 3, p. 585-599 15 p.

    Research output: Contribution to journalArticle (Academic Journal)

    Open Access
    File
  • 1 Citation (Scopus)
    279 Downloads (Pure)

    Investigation of the structural requirements for N-methyl-D-aspartate receptor positive and negative allosteric modulators based on 2-naphthoic acid

    Irvine, M. W., Fang, G., Sapkota, K., Burnell, E. S., Volianskis, A., Costa, B. M., Culley, G., Collingridge, G. L., Monaghan, D. T. & Jane, D. E., 15 Feb 2019, In : European Journal of Medicinal Chemistry. 164, p. 471-498 28 p.

    Research output: Contribution to journalArticle (Academic Journal)

    Open Access
    File
  • 3 Citations (Scopus)
    81 Downloads (Pure)

    Supervised Work

    Development of GluK2 selective kainate receptor antagonists and investigations into the roles of the NMDA receptor subunit GluN2D in hippocampal synaptic plasticity

    Author: Eapen, A., 28 Nov 2019

    Supervisor: Jane, D. (Supervisor) & Lightman, S. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

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