| Prions, misfolded isoforms of endogenous cellular proteins, are a novel class of infectious agents capable of replicating independent of a nucleic acid counterpart. Prions have gained notoriety with the realization that diseases such as Bovine Spongiform Encephalopathy (mad cow disease) and human Creutzfeldt-Jacob Disease are caused by these rogue infectious agents. [PSI +], [RNQ+] and [URE3], prions of the yeast Saccharomyces cerevisiae, are infectious isoforms of the cellular proteins Sup35, Rnq1, and Ure2, respectively. When present in the prion form, these proteins have a tendency to form insoluble aggregates in vivo and in vitro, and can be analyzed using such tools as affinity chromatography, differential centrifugation, and fluorescence microscopy. The premise of this work is to use these tools to characterize other cellular proteins that interact with and influence prion protein aggregation and toxicity. Novel roles of for chaperone proteins, cytoskeletal networks, and cellular death programs are explored. Ultimately, understanding the mechanisms of prion aggregate assembly and disassembly will provide fundamental information for the development of therapies for aggregation-related disorders in higher eukaryotes. |
