title: The MYpop toolbox: Putting yeast stress responses in cellular context on single cell and population scales.
abstract: Systems biology holds the promise to integrate multiple sources of information in order to build ever more complete models of cellular function. To do this, the field must overcome two significant challenges. First, the current strategy to model average cells must be replaced with population based models accounting for cell-to-cell variability. Second, models must be integrated with each other and with basic cellular function. This requires a core model of cellular physiology as well as a multiscale simulation platform to support large-scale simulation of culture or tissues from single cells. Here, we present such a simulation platform with a core model of yeast physiology as scaffold to integrate and simulate SBML models. The software automates this integration helping users simulate their model of choice in context of the cell division cycle. We benchmark model merging, simulation and analysis by integrating a minimal model of osmotic stress into the core model and analyzing it. We characterize the effect of single cell differences on the dynamics of osmoadaptation, estimating when normal cell growth is resumed and obtaining an explanation for experimentally observed glycerol dynamics based on population dynamics. Hence, the platform can be used to reconcile single cell and population level data.
authors.affiliation: Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Spiesser
authors.affiliation: Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kühn
authors.affiliation: Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Krantz
authors.affiliation: Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany. edda.klipp@biologie.hu-berlin.de.
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
mesh_terms: D000222:Adaptation, Physiological; D002453:Cell Cycle; D008954:Models, Biological; D009997:Osmotic Pressure; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development*; D059010:Single-Cell Analysis / Q000379:methods*; D012984:Software; D049490:Systems Biology
keywords: Cell cycle; Growth and division; Hyperosmotic stress; Multiscale modeling; Saccharomyces cerevisiae