Coordination of gene expression within the mammalian circadian timing system
In mammals, virtually all physiological processes undergo daily oscillations, which are coordinated by a hierarchically organized circadian timing system. A pacemaker residing in the suprachiasmatic nucleus (SCN) orchestrates self-sustained and cell autonomous oscillators present in nearly all body cells. As indicated by their name (circa diem means about a day) circadian clocks can measure time only approximately. Thus, depending on the species the period length determined under constant conditions is somewhat longer or shorter than 24 hours. Therefore, in order to stay in resonance with geophysical time the SCN pacemaker must be synchronized each day by light-dark cycles and other external timing cues. In turn, the SCN must phase-entrain the countless oscillators in peripheral tissues to coordinate circadian physiology. A major aim of our research projects is to identify signaling pathways participating in the phase-entrainment of peripheral timekeepers. To this end we developed novel tools allowing us to identify and study signals depending on feeding-fasting rhythms, previously shown to be the dominant Zeitgebers for circadian clocks of most tissues, blood-borne signals and body temperature-dependent cues. Synthetic Tandem Repeat Promoter screening (STAR-PROM) revealed that daily oscillations in actin and tubulin cytoskeleton dynamics participate in the synchronization of circadian clocks. Another novel technology, RT-Biolumicording, allows us to record circadian gene expression in real time in freely moving mice. Using this approach, we can determine the kinetics of phase shifting, a parameter that is much more sensitive to the disruption of signaling pathways than the steady-state phase. The results indicate that the SCN uses both indirect pathways, depending on feeding rhythms, and more direct, feeding-independent pathways to synchronize circadian clocks in the liver and other peripheral tissues.
Date:
1 June 2016, 16:00
Venue:
Sherrington Building, off Parks Road OX1 3PT
Venue Details:
Sherrington Library
Speaker:
Professor Ulrich Schibler (Department of Molecular Biology at the University of Geneva)
Organising department:
Nuffield Department of Clinical Neurosciences
Organiser:
Claire Beauchamp (University of Oxford)
Host:
Sleep and Circadian Neuroscience Institute
Part of:
Nuffield Department of Clinical Neurosciences
Topics:
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Claire Beauchamp
