Section: Application Domains

Coupled models of the cell cycle and the circadian clock

Recent advances in cancer chronotherapy techniques support the evidence that there exist important links between the cell cycle and the circadian clock genes. One purpose for modeling these links is to better understand how to efficiently target malignant cells depending on the phase of the day and patient characterictics. These questions are at the heart of our collaboration with Franck Delaunay (CNRS Nice) and Francis Lévi (Univ. Warwick, GB, formerly INSERM Hopital Paul Brousse, Villejuif) and of our participation in the ANR Hyclock project and in the submitted EU H2020 C2SyM proposal, following the former EU EraNet Sysbio C5Sys and FP6 TEMPO projects. In the past, we developed a coupled model of the Cell Cycle, Circadian Clock, DNA Repair System, Irinotecan Metabolism and Exposure Control under Temporal Logic Constraints (Elisabetta De Maria, François Fages, Aurélien Rizk, Sylvain Soliman. Design, Optimization, and Predictions of a Coupled Model of the Cell Cycle, Circadian Clock, DNA Repair System, Irinotecan Metabolism and Exposure Control under Temporal Logic Constraints. Theoretical Computer Science, 412(21):2108 2127, 2011.). We now focus on the bidirectional coupling between the cell cycle and the circadian clock and expect to gain fundamental insights on this complex coupling from computational modeling and single-cell experiments.