Reed B. Wickner

National Institutes of Health

Election Year: 2000
Primary Section: 26, Genetics
Secondary Section: 21, Biochemistry
Membership Type: Member

Research Interests

I am interested in viruses and prions (infectious proteins) and their interactions with their eukaryotic host cells. My colleagues and I have described several prions and RNA viruses of the yeast Saccharomyces, and are studying these as models for similar entities in mammals. We have examined the mechanisms of RNA virus replication, transcription, and packaging and mechanisms of translation of viral mRNA. We have found cellular genes needed to propagate these elements and host systems that limit the ability of RNA viruses to propagate and thus limit their pathogenicity. We are now investigating the mechanisms of prion generation and propagation using the [URE3], [PSI] and [PIN] prions of the Ure2, Sup35 and Rnq1 proteins of yeast. We have shown that the amyloids underlying these three prions have an in-register parallel beta sheet architecture and proposed how this may explain the ability of yeast prions proteins to template their structure and thus to act as genes. We have shown that the [PSI] and [URE3] prions can be lethal or toxic to cells, and, perhaps for this reason, we find that wild yeast strains have polymorphisms of Sup35p and Rnq1p that limit the spread of prions within the species. We find that the Btn2 and Cur1 proteins are capable of curing the [URE3] prion, and are interested in understanding the mechanism of this effect.

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