Data-driven models of circadian output regulation in mammals

The circadian clock regulates most processes in mammalian physiology in a time of day-dependent manner. Research thus far has focused on understanding this core-clock mechanism that generates oscillations in single cells. Interestingly, the molecular, hormonal and neuronal outputs of the clock act as links within the clock network, but these links are poorly understood. I address this gap using a combination of data-analysis, modeling and theory. Glucocorticoids (GCs) are a key link between the master and peripheral clocks. My first objective is to quantify the effect of GCs on the peripheral clock-controlled genes in key metabolic tissues and thus to infer the mechanisms of co-regulation by the master and peripheral clocks. The master clock also controls complex circadian patterns of rest and activity. My second objective is to quantify the regulation of behavioral activity at different timescales by the master clock and whether there is feedback from behavior to the clock.