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Professor David Jane

Professor David Jane

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

Professor in Chemical Pharmacology

Area of research

Development of pharmacological tools for glutamate receptors

Office G24
Biomedical Sciences Building,
University Walk, Bristol BS8 1TD
(See a map)

+44 (0) 117 331 1409

Summary

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.

 

Activities / Findings

The design, synthesis and pharmacological characterisation of:

  • Antagonists for GluR5 and GluR6 containing kainate receptors.
  • Agonists and antagonists for mGlu8 receptors.
  • Subunit selective competitive NMDA receptor antagonists.
  • Characterisation of kainate and metabotropic glutamate receptors expressed in the neonatal rat spinal cord.


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Teaching

Pharmacology Years 1, 2 and 3. Lectures on the following topics:
Drugs as molecules, drugs in solution, drug discovery and development
Introduction to the pharmacology of excitatory amino acid receptors
Design of CNS drugs
Metabotropic glutamate receptor pharmacology
The role of nitric oxide in CNS function

Keywords

  • Glutamate
  • organic chemistry
  • drug design
  • molecular modelling
  • spinal cord

Skills

  • Brain ischaemia
  • epilepsy
  • schizophrenia
  • pain

Processes and functions

  • Synaptic transmission
  • learning and memory

Methodologies

  • Ion-exchange and silica gel chromatography
  • high voltage paper electrophoresis
  • NMR spectroscopy
  • computer-aided molecular modelling
  • organic chemical synthesis
  • electrophysiology
  • radioligand binding

Links

Selected publications

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Recent publications

View complete publications list in the University of Bristol publications system

Networks & contacts

  • Members of the MRC Centre for synaptic plasticity - Bristol
  • Dr Eamonn Kelly - Dept Pharmacology - Bristol
  • Dr Rebecca Sitsapesan - Dept of Pharmacology - Bristol
  • Prof. Tom Salt - UCL
  • Dr Dan Monaghan - University of Nebraska - Omaha - USA
  • Dr Martin Croucher - Imperial College - London

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