The physiology and behavior of mammals are subjected to daily oscillations that are driven by an endogenous circadian clock. The mammalian circadian clock is composed of a central pacemaker in the suprachiasmatic nucleus (SCN) in the brain that coordinates subsidiary oscillators in most peripheral tissues. The circadian clock can measure time only approximately and therefore must be readjusted every day by external time cues (Zeitgebers) in order to stay in resonance with the geophysical time. The central pacemaker in the brain is entrained by light-dark cycles and is thought to synchronize subsidiary oscillators in peripheral organs by driving cyclic feeding behavior.
The rhythm-generating molecular circuitry is thought to rely on the opposing effects of transcriptional activators and repressors that generate a negative feedback loop. This feedback loop mechanism induces circadian gene expression both in cultured cells and living animals. Experimental evidence suggests a strong interplay between metabolism and circadian clocks. The dominance of feeding cycles as a Zeitgeber for peripheral clocks implies that these clocks have important roles in nutrient processing and energy homeostasis. Indeed, gene expression profiling studies have revealed that many cyclically expressed genes are involved in various cellular metabolic pathways. Furthermore, circadian clocks seem to respond to nutrients and to the cellular metabolic state, however, little is known regarding the molecular mechanisms that adjust body clocks to the cellular metabolic state.
Our main research interest is to explore the interplay between the cellular metabolic state and circadian clocks, and to further identify the underling molecular mechanisms. We are, in particular, interested in further addressing the possible roles of NAD+/NADH in the function of circadian clocks. To these aims, we intend to employ a diverse arsenal of biological experimentation approaches. These include biochemical and molecular biology methods using different cultured cells and mice strains together with behavioral studies and in vivo imaging in living animals.