Modelling the Circadian Oscillator at two levels: The effect of a RNA-Binding Protein (RBP) on the dynamics of the molecular clock and implications of different connectivity architectures on the synchronization of SCN

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

Berlín

Workshop; Chronobiology Summer School 2012; 2012

Institute for Theoretical Biology, Charité and Humbold University

<!-- @page { margin: 2cm } P { margin-bottom: 0.21cm } -->Most living beings 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 mechanism is driven by a set of genes, called clock genes which interact in oscillatory transcriptional networks within cells. The majority of mammalian cells have a circadian molecular clock and they are coordinated by a master circadian pacemaker in the mammalian brain called the suprachiasmatic nucleus (SCN). The SCN consists of about 20,000 neurons and is responsible for keeping synchronized all the circadian clocks of the body with each other, allowing the proper function of the circadian timing system. In this work we show:1)-The effect of a RBP on the dynamics of the molecular clock. Numerous observations have revealed the importance of post-transcriptional regulation on circadian gene expression (Garbarino-Pico and Green, 2007). Recent studies have demonstrated that several clock genes are post-translationally regulated by RBPs (Lowrey and Takahashi et al., 2011). In the present work we show numerical results obtained by using deterministic mathematical models in which we have studied how the dynamics of the circadian molecular clock is affected by a RBP. We found that depending on the values of the RBP-associated parameters, the period and amplitude of the oscillator are affected. The magnitude of those changes depend on whether the repression of transcription is assumed as a cooperative or non-cooperative event.2)-Implications of different connectivity architectures on the synchronization of SCN. The SCN can be considered as a complex network which dynamically works in sync. In the present work we explore how topology of connections can influence the spatio-temporal organization of oscillating neurons within the SCN. We present a comparative study of the synchronization of circadian neuronal clocks when they have different kinds of connectivity architectures. In particular, we analyze the model when defined on a two-dimensional complex network.