STRAIN PROPERTIES OF THE PRION PROTEIN

Project: Research project

Project Details

Description

DESCRIPTION: The long-term objective of the research is to define the role
of the prion protein in the neuropathogenesis of strain diversity for the
transmissible spongiform encephalopathies (TSEs). Specifically, Dr. Bessen
will test the hypothesis that the pathogenicity of TSE strains is
determined, in part, by the properties of the prion protein that comprises
each strain. In Aim #1, the applicant will develop a fluorometric cell-free
conversion assay for PrP-res formation using thioflavin T. In Aim #2, the
applicant will utilize an in situ PrP conversion assay to determine the
brain distribution and rate of conversion of PrPC to strain-specific PrP-res
isoforms. This assay will also be used to define the role of anti-TSE drugs
in the conversion reaction, to probe the mechanism of drug inhibition, and
to rapidly screen for new inhibitors or accelerators of PrP-res formation.
Finally, in Aim #3 the applicant will develop PrP-res fibril extension
assays that utilize electron microscopy and high-definition photomicroscopy
to examine the kinetics and polarity of PrP-res fibril formation. For each
of the aims, the hyper (HY) and drowsy (DY) strains of transmissible mink
encephalopathy (TME) will be examined in order to determine the role of
strain-specific PrP-res in the neuropathogenesis of strain diversity.
StatusFinished
Effective start/end date7/2/985/31/04

Funding

  • National Institute of Neurological Disorders and Stroke: $100,457.00

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