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Kinetic and equilibrium binding studies with PrP proteins

Reference	BBS/E/I/00000748
Principal Investigator / Supervisor	Dr Alan Bennett
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	55,930
Status	Completed
Type	Institute Project
Start date	01/04/2000
End date	31/03/2003
Duration	36 months

Abstract

Prion protein is commonly associated with scrapie high titre infective fractions and its presence is required for the development of TSE pathology. Little is known of the normal cellular function of the protein and it is a paradox that a protein that is highly conserved in evolution appears not to be essential for life. Understanding the function of the protein both in the healthy and TSE-diseased states are fundamental research goals. Insights are sought at the molecular level to define to which molecules the prion protein binds and also the strength and speed of these interactions. We have already demonstrated that anti- scrapie prophylactic polyanions bind directly to the prion protein and that this polyanion binding is dependent on the presence of divalent metal ions. Recently, polycationic polyamines, the electrostatic opposites of polyanions, have been show to have prophylactic potency. Cell-free systems have shown to be capable of converting cellular prion protein to the scrapie-associated form if seeded by the disease-linked form. The cell biology of the prion protein is concerned with the production, function and degradation of the protein in health and disease. These processes are mediated by numerous binding events. Experiments on these interactions and the effects of the environment (e.g pH) should help studies on the normal function of the protein and why its is necessary for TSE pathogenesis. The objectives of the project are to use biophysical techniques (especially surface plasmon resonance) together with mutagenesis and chemical modification-protection to measure the binding of PrP to a variety of ligand groups. These studies will allow the sites of interactions on the prion protein to be more closely defined.

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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