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Induction of yeast prions by oxidative stress

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  • Full or part time
    Prof C M Grant
    Prof M Ashe
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Prions are novel protein-only infectious agents associated with a group of transmissible neurodegenerative diseases typified by human Creutzfeldt Jakob Disease (CJD). Although CJD are rare diseases, they share many pathological features with other more common, non-infectious diseases of the brain such as Alzheimer’s Disease. In spite of its infectious nature, the majority of cases of human CJD (~80%) appear spontaneously, without any evidence of the associated infectious entity, the prion. However, the molecular basis of how prions form spontaneously into infectious amyloid-like structures is poorly understood at present. Prions are also found in the yeast Saccharomyces cerevisiae and we have used one such prion – called [PSI+] – as a model to identify what triggers the spontaneous formation of a prion in the cell. The frequency with which the yeast [PSI+] prion form of Sup35 arises de novo is controlled by a number of genetic and environmental factors. We have shown that in cells lacking key antioxidants, the frequency of de novo formation of [PSI+] is greatly elevated. This points to oxidative damage as one of the triggers of de novo prion formation. The aim of this project is to establish the role of oxidation in prion formation.

Funding Notes

This project has a Band 1 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/).

Informal enquiries may be made directly to the primary supervisor.

References

Sideri, T.C., Stojanovski, K., Tuite, M.F. and Grant, C.M. (2010) Ribosome-associated peroxiredoxins suppress oxidative-stress induced de novo formation of the [PSI+] prion in yeast. Proc. Natl. Acad. Sci. U A. 107:6394-6399.

Sideri, T.C., Koloteva-Levine, N., Tuite, M.F. and Grant, C.M. (2011) Methionine oxidation of Sup35 induces formation of the [PSI+] prion in a yeast peroxiredoxin mutant. J. Biol. Chem. 286:38924-31



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