No abstract

State-space models (SSMs) are an important modeling framework for analyzing ecological time series. These hierarchical models are commonly used to model population dynamics, animal movement, and capture-recapture data, and are now increasingly being used to model other ecological processes. SSMs are popular because they are flexible and they model the natural variation in ecological processes separately from observation error. Their flexibility allows 1 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

BackgroundYeast (Saccharomyces cerevisiae) prions are efficiently propagated and the on-going generation and transmission of prion seeds (propagons) to daughter cells during cell division ensures a high degree of mitotic stability. The reversible inhibition of the molecular chaperone Hsp104p by guanidine hydrochloride (GdnHCl) results in cell division-dependent elimination of yeast prions due to a block in propagon generation and the subsequent dilution out of propagons by cell division.Principal FindingsAnalysing the kinetics of the GdnHCl-induced elimination of the yeast [PSI+] prion has allowed us to develop novel statistical models that aid our understanding of prion propagation in yeast cells. Here we describe the application of a new stochastic model that allows us to estimate more accurately the mean number of propagons in a [PSI+] cell. To achieve this accuracy we also experimentally determine key cell reproduction parameters and show that the presence of the [PSI+] prion has no impact on these key processes. Additionally, we experimentally determine the proportion of propagons transmitted to a daughter cell and show this reflects the relative cell volume of mother and daughter cells at cell division.ConclusionsWhile propagon generation is an ATP-driven process, the partition of propagons to daughter cells occurs by passive transfer via the distribution of cytoplasm. Furthermore, our new estimates of n0, the number of propagons per cell (500–1000), are some five times higher than our previous estimates and this has important implications for our understanding of the inheritance of the [PSI +] and the spontaneous formation of prion-free cells.

Certain yeast cells contain proteins that behave like the mammalian prion PrP and are called yeast prions. The yeast prion protein Sup35p can exist in one of two stable forms, giving rise to phenotypes [PSI(+)] and [psi(-)]. If the chemical guanidine hydrochloride (GdnHCl) is added to a culture of growing [PSI(+)] cells, the proportion of [PSI(+)] cells decreases over time. This process is called curing and is due to a failure to propagate the prion form of Sup35p. We describe how curing can be modelled, and improve upon previous models for the underlying processes of cell division and prion segregation; the new model allows for asymmetric cell division and unequal prion segregation. We conclude by outlining plans for future experimentation and modelling.

propagons ͉ Hsp104 ͉ ␣-factor