Heather L. True-Krob, Ph.D.

Associate Professor
Cell Biology and Physiology

Molecular Cell Biology Program
Molecular Genetics and Genomics Program
Molecular Microbiology and Microbial Pathogenesis Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-362-3934

  • 314-362-3927

  • 314-362-7463

  • 8228

  • 413 McDonnell Sciences Building

  • heather.true@wustl.edu

  • http://www.truelab.wustl.edu/

  • amyloid, chaperones, epigenetics, neurodegeneration, prion, yeast

  • Epigenetic regulation of phenotypes by propagation of prions in yeast

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:

Tank EMH and True HL. Disease-associated mutant ubiquitin causes proteasomal impairment and enhances the toxicity of protein aggregates. PLoS Genetics 2009 5(2): e1000382.

Bardill JP and True HL. Heterologous prion interactions are altered by mutations in the prion protein Rnq1p. Journal of Molecular Biology 2009 388:583-596.

Bardill JP, Dulle J, Fisher J and True HL. Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion. Prion 2009 3:151-60.

Kalastavadi TB and True HL. Prion protein insertional mutations increase aggregation propensity but not fiber stability. BMC Biochem 2008 17:9. Listed as Highly Accessed.

Tank EMH, Harris DA, Desai AA and True HL. Prion protein repeat expansion results in increased aggregation and reveals phenotypic variability. Mol Cell Biol 2007 27:5445-5455.

Last Updated: 8/4/2011 1:03:36 PM

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