Browsing by Author "Thieffry, Denis"

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    Dynamical modeling of syncytial mitotic cycles in Drosophila embryos
    Calzone, Laurence; Thieffry, Denis; Tyson, John J.; Novak, Bela (Nature Publishing Group, 2007-07-01)
    Immediately following fertilization, the fruit fly embryo undergoes 13 rapid, synchronous, syncytial nuclear division cycles driven by maternal genes and proteins. During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins. In this paper, we propose a dynamical model for the molecular events underlying these early nuclear division cycles in Drosophila. The model distinguishes nuclear and cytoplasmic compartments of the embryo and permits exploration of a variety of rules for protein transport between the compartments. Numerical simulations reproduce the main features of wild-type mitotic cycles: patterns of protein accumulation and degradation, lengthening of later cycles, and arrest in interphase 14. The model is consistent with mutations that introduce subtle changes in the number of mitotic cycles before interphase arrest. Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations. The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism.
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    SBML Level 3: an extensible format for the exchange and reuse of biological models
    Keating, Sarah M.; Waltemath, Dagmar; Koenig, Matthias; Zhang, Fengkai; Draeger, Andreas; Chaouiya, Claudine; Bergmann, Frank T.; Finney, Andrew; Gillespie, Colin S.; Helikar, Tomas; Hoops, Stefan; Malik-Sheriff, Rahuman S.; Moodie, Stuart L.; Moraru, Ion I.; Myers, Chris J.; Naldi, Aurelien; Olivier, Brett G.; Sahle, Sven; Schaff, James C.; Smith, Lucian P.; Swat, Maciej J.; Thieffry, Denis; Watanabe, Leandro; Wilkinson, Darren J.; Blinov, Michael L.; Begley, Kimberly; Faeder, James R.; Gomez, Harold F.; Hamm, Thomas M.; Inagaki, Yuichiro; Liebermeister, Wolfram; Lister, Allyson L.; Lucio, Daniel; Mjolsness, Eric; Proctor, Carole J.; Raman, Karthik; Rodriguez, Nicolas; Shaffer, Clifford A.; Shapiro, Bruce E.; Stelling, Joerg; Swainston, Neil; Tanimura, Naoki; Wagner, John; Meier-Schellersheim, Martin; Sauro, Herbert M.; Palsson, Bernhard; Bolouri, Hamid; Kitano, Hiroaki; Funahashi, Akira; Hermjakob, Henning; Doyle, John C.; Hucka, Michael (2020-08)
    Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developedSBMLLevel 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades ofSBMLand a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and howSBMLLevel 3 provides the foundation needed to support this evolution.