Julie A. Williams
Assistant Professor

Circadian and homeostatic mechanisms of sleep

Sleep is associated with many behavioral and physiological processes such as learning. memory. mood. aging. and development. Historically. approaches to sleep research have involved identifying regions of the mammalian brain that are required for sleep induction or wakefulness. While anatomical. pharmacological. and electrophysiological studies have indeed defined the neural circuitry underlying sleep mechanisms. little is known about the genetic and molecular basis of sleep. Our approach to this challenging problem is to investigate the mechanisms of sleep in a model organism. Drosophila melanogaster. Many features of Drosophila cell biology are highly conserved and have historically provided valuable information that is directly relevant to humans. Some examples include advances in cancer biology and circadian rhythms. Our goal is to use this model organism to make similar advances in the field of sleep research.

Do flies actually sleep? Resting behavior in flies is characterized by immobility. reduced sensory responsiveness. and a rest recovery period. or rebound in response to rest deprivation. The rest rebound is proportional to the length of deprivation. indicating that rest is regulated in a homeostatic manner. Rest in flies is also consolidated. or restricted to several consecutive hours at a given time of day. indicating that it is controlled by the circadian clock. Based on these criteria. we have concluded that rest in Drosophila is a sleep-like state. Sleep is controlled by two different processes. One process is homeostatic. which determines how much sleep occurs depending on the length of time spent awake. and the other process is circadian. which determines when or what time of day sleep occurs. Our overall aim is to identify the molecular basis of circadian and homeostatic mechanisms of sleep. We are using molecular. genetic and behavioral approaches to identify the components of each of these systems.

Selected Publications

Williams JA, Sathyanarayanan S, Hendricks, JC, Sehgal A (2007) Interaction between sleep and the immune response in Drosophila: A role for the NFkB Relish. Sleep 30 (4): 389-400.

Williams JA (2004) Molecular analysis of circadian rhythms: Non-mammalian vertebrates. In: A Sehgal (Ed). Molecular Biology of Circadian Rhythms. John Wiley & Sons: New York.

Williams JA. Su HS. Bernards A. Field J. Sehgal A (2001) A circadian output in Drosophila mediated by Neurofibromatosis-1 and Ras/MAP kinase. Science 293: 2251-2256.

Williams JA. Sehgal A. (2001) Molecular components of the circadian system in Drosophila. Ann Rev Physiol 63: 729-755.

Hendricks JC. Williams JA. Panckeri K. Kirk D. Yin J C-P. Sehgal A (2001) A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nature Neurosci 4(11): 1108-1115.

Hendricks JC. Finn SM. Panckeri KA. Chavkin J. Williams JA. Sehgal A. Pack AI (2000) Rest in Drosophila is a sleep-like state. Neuron 25(1): 129-138.