IFEG   20353
INSTITUTO DE FISICA ENRIQUE GAVIOLA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Modelling the organization and function of circadian clocks: from cells to tissue
Autor/es:
REVELLI, J.A.; TAMARIT, F.A.; ROMÁN DEBRÁS, M.D.; GUIDO, M. E.; NIETO, P.S.; GARBARINO-PICO, E.; CONDAT, C.A.
Lugar:
San Miguel de Tucumán
Reunión:
Congreso; III Latin American Federation of Biophysical Societies (LAFeBS) IX IberoAmerican Congress of Biophysics XLV, Reunión Anual SAB; 2016
Resumen:
Predictable environmental changes have been critical to the temporal organization of most living beings. Organisms have developed endogenous circadian clocks, which generate daily variations in biological processes, with periods close to 24 h. At the single cell level, circadian clocks are based on a set of clock genes and proteins expressed in a circadian fashion as a consequence of their mutual interactions based on interconnected feedback loops. Translation of some clock proteins, such as PER, is affected by regulatory proteins and/or microRNAs, but the role of translational regulation in the circadian clock dynamics is not fully understood. We hypothesize that translational regulation produces changes in the kinetics of PER synthesis. Using a mathematical model of the core molecular clock we describe different putative kinetic mechanisms of PER synthesis and their effects on the molecular clock dynamics. In mammals, a master circadian pacemaker in the brain, the suprachiasmatic nuclei (SCN), is composed of cellular circadian clocks able to communicate with each other, sync their activity and hence become a precise and robust biological clock, able to drive circadian rhythms at physiological and behavioral levels. The expression of clock proteins within a SCN slice displays a specific spatio-temporal pattern, characterized by the heterogeneity of their phase peaking. The mechanisms by which these phase relationships are established are not well understood, but depend on the integration of multiple intercellular signals, which ultimately define the functional connectivity of the SCN. We use a model of circadian cellular oscillators coupled through different network architectures to simulate the dynamical behavior observed in SCN slices. We then present the characterization of the emerging dynamical behavior of our models according to their topology and show how these models can be used to infer the functional connectivity of the SCN.