Rosamaria Cannavo

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ABSTRACT “Coupled oscillators are not only of great biological importance, but also very interesting from a dynamical systems point of view. In a systems biology context, the interconnection between two periodic processes such the circadian rhythm and the cell cycle represents an ideal analyzable system at the single-cell level. The analysis of a large dataset from time-lapse imaging of single mouse fibroblast showed, in our previous study, that circadian and cell cycle are robustly synchronized. This synchronization state is observed over a wide range of conditions resulting from a predominant influence of the cell cycle on the circadian cycle. Moreover, parameters of the coupling functions has been identified with stochastic modeling of two interacting phase oscillators. Here, we reconstruct a non-parametric model of the phase dynamics, identifying new potential interactions between the two processes. This allows us to make more specific predictions on precise cell cycle events that could influence the circadian clock, such the condensation of chromosomes coinciding with transcriptional shutdown, and subsequently testing those prediction using different markers of cell cycle events. By analyzing several conditions we found that the phase relationship of the two systems presents shifts characteristic of resonating oscillators. In conclusion, we highlight how the use of a statistical model allows the understanding of the interaction between two important cellular processes by reducing the complex dynamics to a low dimensional phase model. ”