title: Comparative study of circadian oscillatory network models of Drosophila.
abstract: The circadian clock of Drosophila is a model pathway for research in biological clock mechanisms, both with traditional experimental approaches and with emerging systems biology approaches utilizing mathematical modeling and in silico computer simulation. Dynamic diurnal oscillations are achieved by the complex interaction of components as a system, and mathematical reconstruction has proven to be an invaluable means of understanding such systematic behavior. In this study, we implemented eight published models of the Drosophila circadian clock in Systems Biology Markup Language (SBML) for comparative systems biology studies using E-Cell Simulation Environment version 3, to examine the system-level requirements for the clock mechanism to be robust, by calculating the period and amplitude sensitivity coefficients with simulation experiments. While all models were generally robust as determined by the network topology of the oscillatory feedback loop structure, existing models place relatively strong emphasis on transcription regulation, although this is a limitation on robustness. We suggest that more comprehensive modeling including protein phosphorylation, polymerization, and nuclear transport with regard to amplitude sensitivity will be necessary for understanding the light entrainment and temperature compensation of circadian clocks.
authors.affiliation: Institute for Advanced Biosciences, Keio University, Fujisawa 252-8520, Japan. snowy@sfc.keio.ac.jp
authors.forename: Yukino
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Arakawa
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaizu
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Miyoshi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003198:Computer Simulation; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008954:Models, Biological; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software
chemical_list: D029721:Drosophila Proteins