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DISSECTING THE MECHANISM OF PRION FORMATION WITH A PERMISSIVE HOST

Investigators
Supattapone, Surachai
Institutions
Dartmouth College
Start date
2018
End date
2022
Objective
Project SummaryPrion diseases are infectious neurodegenerative diseases caused by the inducedconformational change of a host-encoded glycoprotein, PrPC, into a pathogenicconformer, PrPSc. Currently, there are no vaccines or therapies available for theseinvariably fatal diseases, primarily because we do not understand the mechanism ofPrPSc formation.Interestingly, there are large differences in host susceptibility to prion infection betweendifferent animal species. For instance, rabbits appear to be resistant to all prion strains,while bank voles appear to be a universal host. This variation, which is dependent onPrP sequence, provides us with a unique opportunity to identify the key steps in PrPScformation shared by all species. Using rigorous biochemical tools developed in ourlaboratory, we will exploit these naturally occurring differences in host susceptibility todissect the mechanism of prion replication. Specifically, this powerful comparativebiochemistry approach will be used to accomplish the following aims:1. Directly test the protein-only hypothesis of prion infectivity.2. Identify and characterize PrPC domains that control susceptibility to prion conversion.3. Determine whether cofactor molecules and post-translational modifications restrictthe host range of prion infection.The results of this project will greatly advance our understanding of the prion replicationmechanism. They will also impact our understanding of related, prion-like diseases,such as Alzheimer's and Parkinson's disease.
Funding Source
Nat'l. Inst. of Neurological Disorders and Stroke
Project source
View this project
Project number
1R01NS102301-01A1
Accession number
102301
Categories
Bacterial Pathogens
Viruses and Prions
Commodities
Meat, Poultry, Game