Title (题目): Modeling the cell cycle by differential equations and cellular automata

Speaker (报告人):  Professor Albert Goldbeter (比利时皇家科学院院士)  

                                 Unit of Theoretical Chronobiology, Faculty of Sciences

                                 Université Libre de Bruxelles (ULB)

                                 Brussels, Belgium

Time (时间): 2016-11-3 (星期四) 15:00-16:00

Place (地点): 数学楼二楼报告厅

Abstract (摘要): To gain insight into the dynamics of this major cellular process we developed a detailed computational model for the network of cyclin-dependent kinases (Cdks) driving progression along the successive phases M (mitosis), G1, S (DNA replication) and G2 of the mammalian cell cycle. The model is described by a system of 39 nonlinear, coupled differential equations. A reduced, skeleton model containing only 5 ordinary differential equations yields similar results. The analysis of the models shows how the balance between cell cycle arrest and cell proliferation is controlled by growth factors (GFs) or by the levels of activators (oncogenes) and inhibitors (tumor suppressors) of cell cycle progression. Supra-threshold changes in the level of any of these factors can trigger a switch in the dynamical behavior of the Cdk network corresponding to a bifurcation between a stable steady state, associated with cell cycle arrest, and sustained Cdk oscillations corresponding to cell proliferation. To further study the dynamics of the cell cycle we developed an automaton model in which each cellular automaton switches stochastically between the sequential phases of the cell cycle, which have durations distributed around mean values. This approach is well suited to studying how the fractions of cells in a given cell cycle phase evolve in a cell population. The automaton model can be used to probe the existence of optimal schedules of circadian administration of anticancer drugs that target cells in a particular phase of the cell cycle.

References:

Altinok, A., Lévi, F. & Goldbeter, A. (2007) A cell cycle automaton model for probing circadian patterns of anticancer drug delivery.  Adv Drug Deliv Rev 59, 1036-53.

Altinok A, Gonze D, Lévi F, Goldbeter A. (2011) An automaton model for the cell cycle. Interface Focus 1, 36-47.

Gérard C, Goldbeter A. (2009) Temporal self-organization of the cyclin/Cdk network driving the mammalian cell cycle. Proc Natl Acad Sci USA 106, 21643-21648.

Gérard C, Goldbeter A. (2012) From quiescence to proliferation : Cdk oscillations drive the mammalian cell cycle. Front. Physio. 3:413, doi: 10.3389/fphys.2012.00413

Gérard C, Goldbeter A (2015) Dynamics of the mammalian cell cycle in physiological and pathological conditions. WIREs Syst Biol Med 2015. Doi : 10.1002/wsbm.1325.