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Models for Yeast Prions

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The cytoplasmic heritable determinant [PSI+] of the yeast Saccharomyces cerevisiae exhibits prion-like properties. The properties of yeast prions are studied in the hope that this will enhance the understanding of mammalian prions, which cause mad-cow, Creutzfeldt-Jakob, and related neurodegenerative diseases. When host cells divide, the yeast prions distribute themselves without loss over the daughter cells. Experimental data provide information on how the proportion of cells with prions decreases over time when prion replication is inhibited. One feature of scientific interest is the unknown mean number, n0 , of prions assumed to be present in the cells at the start of the experiment. We develop several stochastic models and by fitting them to the data, we obtain substantially larger estimates of n0 compared with a previous analysis. An interesting feature of a model with constant cell generation times is that the predicted proportion of cells with prions varies over time as a sequence of linked hyperbolic curves. Avenues for future research are outlined, which relax simplifying assumptions made in the models. We make several recommendations for the design of future experiments.
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Keywords: Binomial distribution; Cell generation time distributions; Curing curves; Experimental design; Gamma distribution; Linked hyperbolic curves; Multiple optima; Survival

Document Type: Research Article

Affiliations: 1: Institute of Mathematics and Statistics, University of Kent, Canterbury, Kent CT2 7NF, England 2: Department of Biochemistry, Biocenter Oulu, P.O. Box 3000, FIN-90014 Oulun yliopisto, Finland

Publication date: 01 September 2003

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