CONICET | Buscador de Institutos y Recursos Humanos

Predictable environmental changes have been critical to the temporalorganization of most living beings. Organisms have developed endogenouscircadian clocks, which generate daily variations in biological processes,with periods close to 24 h. At the single cell level, circadianclocks are based on a set of clock genes and proteins expressed in acircadian fashion as a consequence of their mutual interactions basedon interconnected feedback loops. Translation of some clock proteins,such as PER, is affected by regulatory proteins and/or microRNAs, butthe role of translational regulation in the circadian clock dynamics isnot fully understood. We hypothesize that translational regulation produceschanges in the kinetics of PER synthesis. Using a mathematicalmodel of the core molecular clock we describe different putativekinetic mechanisms of PER synthesis and their effects on the molecularclock dynamics. In mammals, a master circadian pacemaker in thebrain, the suprachiasmatic nuclei (SCN), is composed of cellular circadianclocks able to communicate with each other, sync their activity andhence become a precise and robust biological clock, able to drive circadianrhythms at physiological and behavioral levels. The expressionof clock proteins within a SCN slice displays a specific spatio-temporalpattern, characterized by the heterogeneity of their phase peaking. Themechanisms by which these phase relationships are established are notwell understood, but depend on the integration of multiple intercellularsignals, which ultimately define the functional connectivity of the SCN.We use a model of circadian cellular oscillators coupled through differentnetwork architectures to simulate the dynamical behavior observedin SCN slices. We then present the characterization of the emerging dynamicalbehavior of our models according to their topology and showhow these models can be used to infer the functional connectivity of theSCN.105