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Julie Williams
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Assistant Professor
Department of Pharmacology
UMDNJ-Robert Wood Johnson Medical School
Ph.D., 1997, University of British Columbia
Tel: [732] 235-5313
Fax: [732] 235-4850
jwilliams@cabm.rutgers.edu
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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
- 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.
- 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.
- 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.
CABM
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