Section: New Results

Modeling the Cell Cycle

Participants : Elisabetta De Maria, François Fages, Aurélien Rizk, Sylvain Soliman.

Recent advances in cancer chronotherapy techniques support the evidence that there exist some links between the cell cycle and the circadian clock genes [10] . One purpose for modeling the entrainment in period of the cell cycle by the circadian clock is to better understand how to efficiently target malignant cells depending on the phase of the day. This is at the heart of our participation in the EU STREP project TEMPO in collaboration with the BANG project-team.

In [11] , [24] we show how temporal logic constraints, and the new features of BIOCHAM for parameter search, can be used to couple dynamical models. This approach is illustrated by a coupled model composed of:

• a four phases model of the mammalian cell cycle by Novak and Tyson,

• a circadian clock model by Leloup and Goldbeter,

• a DNA damage repair model by Ciliberto et al.,

• a model of irinotecan metabolism by Dimitrio and Ballesta,

• a simple model of drug administration control.

This coupled model allows us to minimize the toxicity of irinotecan on healthy cells, using BIOCHAM's parameter search method applied on the drug administration control law.

In [2] , [3] , purely qualitative models of the cell cycle are shown to provide other useful information, and surprisingly informative results. In [8] , a model of the G1/S transition of the cell cycle is used to find targets for drug resistance.

One important perspective that is common to all this modeling work around the cell cycle is the promise of patient-tailored therapeutics [9] .