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The role of ionotropic glutamate receptors in the regulation of hormone secretion in the endocrine pancreas

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

Project Description

Supervisors: Elek Molnar1, Aniko Varadi2

1School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK. E-mail: [email protected]
2Centre for Research in Biosciences, Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of the West of England, Bristol BS16 1QY, UK. E-mail: [email protected]

Ionotropic glutamate receptors (iGluRs) are ligand gated ion channels that are activated by the major excitatory neurotransmitter glutamate and they are key players in cellular communication throughout the central nervous system. Functional iGluRs were also identified in pancreatic islet cells where they modulate hormone secretion in vitro and in vivo in both rodents and human. However, there are conflicting reports in the literature and the precise molecular compositions and characteristics of iGluRs in pancreatic islet cells are not known. The proposed research aims to define the physiological role of iGluRs in the regulation of hormone secretion in the endocrine pancreas. The molecular organisation, distribution, pharmacological and functional properties and regulation of iGluR subtypes (AMPA, kainate and NMDA receptors) will be studied in human and rodent islets of Langerhans, glucagon secreting alpha-cells and insulin releasing beta-cells using a combination of molecular, pharmacological, biochemical and histological approaches. New pharmacological tools (e.g. biotin-tagged photoreactive affinity ligands and high affinity subunit specific antagonists), wide range of extensively characterised antibodies, transgenic mice and sensitive assays will enable the systematic characterisation of iGluRs in different cell types of the islets of Langerhans. The study will reveal key features of the expressed iGluRs and their involvement in endocrine regulation. It is likely that these receptors participate in the pathomechanism of diabetes mellitus and they should also be considered as potentially important pharmacological targets for future treatment strategies.


Deadline for applications: MIDNIGHT on Tuesday 1st December

Funding Notes

This project is a self-funding project. Although it states 'Applications accepted all year round' we do encourage that the course commences either in January, April, July or September

To apply you need to choose: Faculty of Biomedical Sciences under the ’Faculty’ section, School of Physiology and Pharmacolgy (PhD) under the ’programme choice’ section. Additionally under the ’Research Details’ section, please indicate that you are applying for a self funded project and give the project title and names of supervisors.

References

Molnar E (2012) Glutamate receptors. In: Encyclopedia of Signaling Molecules (ed: Choi S), Springer Reference, pp779-86. ISBN: 978-1-4419-0460-7
Brozzi F, Lajus S, Diraison F, Rajatileka S, Hayward K, Regazzi R, Molnar E, Varadi A (2012) MyRIP interaction with myosin Va on secretory granules is controlled by the cAMP-PKA pathway. Mol Biol Cell 23:4444-4455.
Brice NL, Varadi A, Ashcroft SJH, Molnar E (2002) Metabotropic and GABAB receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells. Diabetologia 45:242-252.
Molnar E, Váradi A, McIlhinney RAJ, Ashcroft SJH (1995) Identification of functional ionotropic glutamate receptor proteins in pancreatic -cells and in islets of Langerhans. FEBS Lett 371:253-257.

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