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Chaperone interactions with PrP
Reference
BS308143
Principal Investigator / Supervisor
Professor Michael Cheetham
Co-Investigators /
Co-Supervisors
Dr Christopher Birkett
Institution
University College London
Department
Institute of Ophthalmology
Funding type
Research
Value (£)
292,752
Status
Completed
Type
Research Grant
Start date
01/07/1997
End date
30/04/2001
Duration
46 months
Abstract
The prion protein (PrP) plays a central role in Transmissible Spongiform Encephalopathy (TSE) disease progression and transmission. It is now clear that conformational changes in the PrP molecule are pivotal in disease pathogenesis. Molecular chaperones have been shown to be important facilitators of protein conformational change in many cellular systems, but their effects upon PrP conformation are little studied. This proposal aims to test the hypothesis that chaperones can modulate PrP conformation and may be involved in disease related conformational changes by studying the biochemical basis of their interaction in vitro. We will analyse chaperone/PrP binding by a variety of methods and delineate the chaperone binding sites in PrP. The effects of hsp70 and co-chaperones on the re- folding of recombinant PrP after denaturation will also be investigated, including analysis of PrPSc and peptide mediated alterations in PrPc conformation. Studies of `prion-like' phenomena in yeast have suggested that manipulation of heat shock proteins and chaperones can inhibit prior activity. Therefore, demonstration that chaperones can mediate changes in PrP conformation may highlight new strategies to combat TSE.
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
Biology of Spongiform Encephalopathies - Phase 3 (BS3) [1996-1997]
Funding Scheme
X – not Funded via a specific Funding Scheme
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