Biologie des systèmes et rythmes cellulaires

Circadian rhythms and systems biology

Unité de chronobiologie théorique, Faculté des sciences, Université Libre de Bruxelles, Campus Plaine, CP 231, B-1050 Bruxelles, Belgique

^* agoldbet@ulb.ac.be

Résumé

Les rythmes cellulaires representent un domaine d’investigation de choix pour la biologie des systemes. Les exemples des rythmes circadiens et du cycle cellulaire montrent comment l’experience et la modelisation permettent de clarifier les conditions dans lesquelles les comportements periodiques surviennent de maniere spontanee au sein des reseaux de regulation cellulaire. Les rythmes circadiens resultent de boucles de retroactions positives et negatives controlant l’expression de genes de l’horloge. Le cycle cellulaire repose sur de multiples regulations entrecroisees au sein d’un reseau de kinases dependantes de cyclines. Dans les deux cas, comme pour d’autres rythmes cellulaires decrits au cours des annees recentes, le comportement periodique represente une propriete emergente des systemes biologiques liee a leurs regulations.

Abstract

Cellular rhythms represent a field of choice for studies in system biology. The examples of circadian rhythms and of the cell cycle show how the experimental and modeling approaches contribute to clarify the conditions in which periodic behavior spontaneously arises in regulatory networks at the cellular level. Circadian rhythms originate from intertwined positive and negative feedback loops controlling the expression of several clock genes. Models can be used to address the dynamical bases of physiological disorders related to dysfunctions of the mammalian circadian clock. The cell cycle is driven by a network of cyclin-dependent kinases (Cdks). Modeled in the form of four modules coupled through multiple regulatory interactions, the Cdk network operates in an oscillatory manner in the presence of sufficient amounts of growth factor. For circadian rhythms and the cell cycle, as for other recently observed cellular rhythms, periodic behavior represents an emergent property of biological systems related to their regulatory structure.