Award details

Molecular studies on scrapie and Bovine spongiform encephalopathy prophylaxis

Reference	BBS/E/I/00000593
Principal Investigator / Supervisor	Dr Alan Bennett
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	4,775
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/09/1997
Duration	6 months

Abstract

This project was a PhD study undertaken by Ms Debbie Brimacombe under the supervision of Dr A D Bennett. The aim was to seek to obtain novel information on the molecular action of known anti-scrapie compounds. 1. Milligram quantities of partially glycosylated soluble recombinant prion protein (recPrP) lacking a GPI tail were produced and highly purified. 2. Mass spectrometry identified that the material was of correct mass and also that in vivo cleavage occurred at the precise site seen in animals. 3. Prophylactic polyanions were successfully biotin labelled and captured on streptavidin-coated surface plasmon resonance biosensor chips (BIACore). 4. The binding of recPrP to polyanions was abolished by EDTA and was strongly stimulated by added divalent metals. 5. Polyanion binding was kinetically complex but competition binding experiments were able to show qualitative linkage between the prophylactic potency of the polyanion and its PrP binding strength. 6. Work on the purified recPrP cleavage fragments and on synthetic PrP peptides showed that the binding of the peptides to polyanions is amino acid sequence specific and that PrP contains at least two well separated polyanion binding domains. A paper based on this work has recently been accepted for referee's assessment (see below), posters were presented at the TSE workshop and to the British Mass Spectrometry Soc. and the thesis written formed the basis of the recent successful Doctoral award to Ms Brimacombe.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
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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