Conference Agenda

Amita Sehgal

Sleep remains a major mystery of biology. Why we spend ~a third of our lives sleeping and what it is that makes us sleepy are major questions about sleep that lack satisfactory answers. There is universal agreement that lack of sleep impairs performance, especially cognitive ability, during waking hours and considerable evidence supports adverse effects of sleep loss on other physiological parameters as well. Thus, sleep may be regarded as important for waking function. However, what happens during sleep to facilitate wake performance and promote health? Driven by the successful use of Drosophila for deciphering molecular mechanisms of the circadian clock, we developed a Drosophila model to address molecular and cellular underpinnings of sleep. Through the use of forward genetic screens, we have identified genes and tissues that affect sleep amount. Coupled with tests of candidate hypotheses for sleep function, we are starting to get a handle on cellular functions of sleep that may be broadly relevant for the brain, and perhaps even the body. Importantly, molecules and mechanisms we’re uncovering in Drosophila appear to be conserved in mammals.

In general, we find that sleep is important for metabolic homeostasis, which includes the clearance of metabolic waste. For instance, we find that autophagy and endocytosis through the blood brain barrier, both of which could facilitate clearance, are regulated by sleep. Our ongoing work implicates sleep in lipid metabolism, in particular. We showed that the peripheral steroid hormone, ecdysone, promotes sleep by mobilizing lipid droplets in glia. And we recently identified a neuron-glia lipid transfer cycle that is regulated by sleep. Conversely, the metabolic status of the animal influences sleep amount. Together this work is leading to an understanding of cellular/molecular processes that underlie sleep.

HHMI, Perelman School of Medicine, University of Pennsylvania, Philadelphia