Modelling the circadian rhythms generation at two levels of biological organization

NIETO, P.S.; ROMÁN DEBRÁS, M.D.; REVELLI, J.A.; GARBARINO-PICO, E.; GUIDO, M. E.; TAMARIT, F.A.

Carlos Paz

Congreso; XLII Annual Meeting of the Argentinian Biophysics Society; 2013

Argentinian Biophysics Society

Most living organisms exhibit physiological and behavioural circadian rhythms with an endogenous period of about 24 h, which can be synchronized and anticipate to periodic cues. At molecular level, the circadian timekeeping is driven by a set of genes, called clock genes, which interact in oscillatory transcriptional networks within cells. In mammals, these clock genes are expressed in cells throughout the whole body and their activity is orchestrated from within the brain, in a tiny structure in the hypothalamus known as the suprachiasmatic nuclei (SCN). The SCN consists of about 20,000 neurons which are diverse and function in a coordinate fashion since they are able to communicate with each other, sync their activity and hence become -as a whole- a biological clock both precise and robust. In this work we present two deterministic mathematical models for studying circadian rhythms generation at two levels. At the cellular level, we have studied how the dynamics of the molecular clock is affected by the translational regulation of clock genes. We found that translational regulation introduces time-delays between the mRNA and protein expression which ultimately affects the period of the molecular clock. At the multicellular level we use a model of circadian oscillators coupled through different network architectures, in order to simulate the dynamical behavior observed in SCN slices. We propose quantitative metrics to characterize the emerging dynamical behavior in the model. We show that these metrics reflect different profiles having their origin in the underlying network topology. We posit that these metrics can be applied to experimental time-series from SCN slices in order to characterize their spatio-temporal organization and potentially dilucidate their functional connectivity.