Interrogation of Genetic and Nutritional Control of Sleep across Seasons - ABSTRACT: Seasonal availability of nutrient constitutes a major driver of organismal physiology that has produced extreme phenotypes such as hibernation, but also seasonal variation in body weight, blood-glucose control, peripheral tissue transcription, and sleep in humans. A central theme of these adaptations is the tradeoff between energy conservation and energy harvesting that drives circannual patterns in feeding and sleeping behavior. The circadian clock segregates sleep and feeding behaviors to distinct phases of the day in coordination with the environmental light/dark cycle, yet little is known about how clock regulation of sleep/feeding adapts to seasonal variation in nutrient and light. My previous postdoctoral research uncovered a phosphorylation event on PER2- S662 that regulates circadian nutrient sensing and synchronization with seasonal photoperiods. My new preliminary data reveals sleep, feeding, energetic, and hypothalamic signaling defects in PER2-S662 phospho- mutant mice that recapitulate seasonal adaptations observed in nature. The overarching goal of this research is to interrogate the role of the clock in seasonal sleep and feeding adaptations. I hypothesize that light and nutrient cues that occur during the summer will drive food intake at the expense of sleep by increasing PER2-S662 phosphorylation. Understanding the mechanisms whereby organisms adapt to the seasons is key for gaining insight into the etiology of disease as humans in modern society are exposed to year-long unhealthy diets and long photoperiods as a result of modern supermarkets and electronic devices. These cues, therefore, signal a constant state of summer that is predicted to disrupt sleep and drive development of obesity. The research and training programs that I have proposed will allow me to establish a novel niche at the intersection of sleep, circadian rhythms, and seasonality that will fuel a productive independent research program into the future.
