Research Abstract:
Prions are protein infectious particles, initially hypothesized to be the causative agent of certain neurodegenerative disorders in mammals. Prion proteins harbor the ability to exist in structurally distinct states associated with functional alterations that undoubtedly have biological consequences. Although in mammals the prion hypothesis is still subject to debate, it is clear that a similar process occurs in yeast. In yeast, prions serve as heritable epigenetic elements and represent a novel mechanism of phenotypic inheritance. Yeast prions have provided a simple model system to study prion propagation. This model has revolutionized the mammalian prion field, as several yeast proteins have been shown to behave as prions. In addition, the properties of yeast prions are reminiscent of several misfolded proteins that result in neurodegenerative disorders and present a tractable model system to understand the nature of such aggregates.
My lab is interested in the biological consequences of yeast prions - in both their capacity to function as a novel epigenetic elements, as well as in their utility to serve as a tractable model for the analysis of protein misfolding and aggregation that mimics important events in several neurodegenerative disorders. We are interested in how prions in yeast impact survival and adaptation. We are also interested in understanding what other prions exist and how broadly prions affect cellular physiology. We are also using prions in yeast to understand how the environment influences protein misfolding and aggregation, a question that has been difficult to address with current model systems of several neurodegenerative disorders.
Selected Publications:
True HL. The battle of the fold: Chaperones take on prions. Trends Genet 2006 22:110-117.
True HL, Berlin I, Lindquist SL. Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 2004 431:184-187.
Causton HC, Ren B, Koh SS, et al. Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 2001 12:323-337.
Jensen MA, True HL, Chernoff YO, Lindquist S. Molecular population genetics and evolution of a prion-like protein in Saccharomyces cerevisiae. Genetics 2001 159:527-535.
True HL, Lindquist SL. A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 2000 407:477-483.
Last Updated: 10/05/2006 |