Perspectives on prions have changed dramatically in recent years. Amyloids, the protein assemblies that underlie prions and numerous other neurodegenerative pathologies, including Alzheimer’s, Huntington’s, and Parkinson’s diseases, have recently been shown to have normal functions in human cells.
Prions also occur in other organisms and are best characterized in the model eukaryote, budding yeast. The ability of these proteins to form prions is, in some cases, essential for their functions in innate immunity and programmed cell death.
The ability of a prion to assemble in many cases depends on the preexistence of other protein assemblies. How does such promiscuity relate to the functional and dysfunctional consequences of prions, and how is it modulated by the cell?
Our lab has developed a state-of-the-art quantitative assay for prion behavior, which will allow me to systematically identify protein interactions that influence prion formation and propagation, and to uncover mechanisms by which cells regulate prions.