title: Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models.
abstract: The eukaryotic cell cycle is robustly designed, with interacting molecules organized within a definite topology that ensures temporal precision of its phase transitions. Its underlying dynamics are regulated by molecular switches, for which remarkable insights have been provided by genetic and molecular biology efforts. In a number of cases, this information has been made predictive, through computational models. These models have allowed for the identification of novel molecular mechanisms, later validated experimentally. Logical modeling represents one of the youngest approaches to address cell cycle regulation. We summarize the advances that this type of modeling has achieved to reproduce and predict cell cycle dynamics. Furthermore, we present the challenge that this type of modeling is now ready to tackle: its integration with intracellular networks, and its formalisms, to understand crosstalks underlying systems level properties, ultimate aim of multi-scale models. Specifically, we discuss and illustrate how such an integration may be realized, by integrating a minimal logical model of the cell cycle with a metabolic network.
authors.affiliation: Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, 1081 HZ Amsterdam, The Netherlands M.Barberis@uva.nl.
authors.forename: Matteo
authors.initials: M
authors.lastname: Barberis
authors.affiliation: Department of Natural and Applied Sciences, Mount Mercy University, Cedar Rapids, IA 52402, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Todd
authors.affiliation: Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Lucas
authors.initials: L
authors.lastname: van der Zee
mesh_terms: D002453:Cell Cycle; D003198:Computer Simulation; D005786:Gene Expression Regulation; D008954:Models, Biological; D009172:Mycology / Q000639:trends*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*
keywords: cell cycle; constraint-based modeling; logical modeling; metabolism; multi-scale modeling; network integration