Award details

GABA receptors: molecular pharmacology, novel ligands

Reference	BBS/E/B/51916219
Principal Investigator / Supervisor	Professor David Sattelle
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	26,459
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/09/1999
Duration	30 months

Abstract

Molecular cloning, sequencing and stable expression in cell lines of a robust GABA receptor subunit homo-oligomer (RDL) has been achieved, and is being extended to provide stable expression of a mutant form of the receptor subunit that is resistant to insecticides of current commercial value such as fipronil. Functional roles of recently identified splice variants of the Rdl gene will be investigated. Initial findings on one variant that differs in a small number of residues close to the GABA binding site have revealed differences in agonist affinity. Multidisciplinarity: Molecular cloning, mutagenesis and functional expression in cell lines and Xenopus oocytes together with electrophysiological assays are combined in studies of wild-type and mutant GABA receptors. The likely benefit of this research is an enhanced basic understanding of ionotropic GABA receptor function. Exploitability: As a naturally occurring A to S substitution has been shown to generate resistance to fipronil, in vitro assays are available to assist in biorational design of Agrochemicals and the prediction of cross-resistance. The work is carried out in collaboration with colleagues at DuPont. The project is relevant to the H&LS and ANRE Foresight and the priorities of Drug Creation and Delivery (also AS Biomolecular Design (as it is identifying molecular targets of commercial insecticides), Integrative Biology (as it brings together genetics, cell biology and physiological approaches to the characterisation of GABA-mediated synaptic transmission); Diagnostic Applications of Molecular Biology as reagents based on the resistant allele offer a screen of wide utility in assessing resistance in pest insect species. Also relevant to AF Animal Health.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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