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| Title: | Factors Affecting Transmission of Prions Between Species | ||
| Objective: | Determine environmental conditions and genetic factors that contribute to the ability to overcome the prion species barrier. Elucidate the structural requirements for the heterotypic protein aggregation that may occur during interspecies prion transmission. | ||
| More Info: | Prion diseases are neurodegenerative protein aggregation disorders that have inherited, sporadic, and infectious origins. Normally, prions from one species are not infectious to another species, so a species barrier against transmission exists. However, there is evidence that the species barrier can be overcome. For example, the prion strain responsible for Bovine Spongiform Encephalopathy ("Mad Cow Disease") in cattle may have infected humans, resulting in new variant Creutzfeldt-Jakob Disease (vCJD). Very little is understood about how the species barrier is maintained or how it is overcome. The goal of this project is to determine environmental conditions and genetic factors that contribute to overcoming the prion species barrier. Understanding the underlying principles of the prion species barrier and how it is overcome may be keys to preventing transmission and to identifying new therapeutic targets.
The species barrier observed with yeast prions mimics that of the mammalian prion protein. A cytosolic protein-protein interaction system in yeast will be used to investigate environmental factors and cellular proteins that influence prion propagation and transmission. Chemical and genetic screens will be conducted to assess environmental conditions and genetic factors that eliminate or weaken the species barrier. Amino acid residues required for the interaction of prion proteins from two different species will also be identified to gain insight on the molecular interface important for heterotypic protein aggregation. | ||
| Agency: | United States Department of Agriculture (USDA) Cooperative State Research, Education, and Extension Service (CSREES) | ||
| Type: | Grant | ||
| Total Funding: | $330,000 | ||
| Start Date: | 2005 | End Date: | 2007 |
| Project Number: | MOR-2004-04254 | ||
| Accession Number: | 0202406 | ||
| Keywords: | prion diseases; PrPSc proteins; prions; strain differences; chronic wasting disease; scrapie; bovine spongiform encephalopathy; disease transmission; pathogenesis; environmental factors; genetic resistance; disease control; Creutzfeldt-Jakob Syndrome; protein-protein interactions, cross-species transmission; species barrier | ||
| Institution: | Washington University | ||
| Investigator(s): | Lisa Strawn (Primary) | ||
| Food Safety Categories: | On-Farm Food Safety Diseases and Poisonings Pathogen Biology | ||
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