Circadian Clocks, Sleep, and Metabolism.

A molecular circadian clock exists not only in the brain, but also in most cells of the body. Research over the past two decades has demonstrated that it directs daily rhythmicity of nearly every aspect of metabolism. It also consolidates sleep-wake behavior each day into an activity/feeding period and a sleep/fasting period. Otherwise, sleep-wake states are mostly controlled by hypothalamic and thalamic regulatory circuits in the brain that direct overall brain state. Recent evidence suggests that hypothalamic control of appetite and metabolism may be concomitant with sleep-wake regulation, and even share the same control centers. Thus, circadian control of metabolic pathways might be overlaid by sleep-wake control of the same pathways, providing a flexible and redundant system to modify metabolism according to both activity and environment.

Roughness and dynamics of proliferating cell fronts as a probe of cell-cell interactions.

Juxtacellular interactions play an essential but still not fully understood role in both normal tissue development and tumour invasion. Using proliferating cell fronts as a model system, we explore the effects of cell-cell interactions on the geometry and dynamics of these one-dimensional biological interfaces. We observe two distinct scaling regimes of the steady state roughness of in-vitro propagating Rat1 fibroblast cell fronts, suggesting different hierarchies of interactions at sub-cell lengthscales and at a lengthscale of 2-10 cells. Pharmacological modulation significantly affects the proliferation speed of the cell fronts, and those modulators that promote cell mobility or division also lead to the most rapid evolution of cell front roughness. By comparing our experimental observations to numerical simulations of elastic cell fronts with purely short-range interactions, we demonstrate that the interactions at few-cell lengthscales play a key role. Our methodology provides a simple framework to measure and characterise the biological effects of such interactions, and could be useful in tumour phenotyping.