Description of Research Expertise
Research Interests
The regulation and function of sleep
Key Words: sleep, ecdysis, molting, behavior, amyloid, neuropeptides
Description of Research
Quiescent behavioral states are universal to the animal world with the most famous and mysterious of these being sleep. Despite the fact that we spend one third of our life sleeping, and despite the fact that all animals sleep, the core function of sleep remains a mystery. In addition, the molecular basis underlying sleep/wake regulation is poorly understood.
We use the nematode C. elegans as a model system to address these questions. C. elegans offers many experimental advantages including powerful genetic tools as well as a simple neuroanatomy.
Growth of C. elegans from an embryo to an adult is punctuated by four molts, during which the animal secretes a new cuticle and sheds its old one. Prior to each molt the worm has a quiescent behavioral state called lethargus. Lethargus has several similarities to sleep including rapid reversibility to strong stimulation, increased sensory arousal threshold, and homeostatic regulation. Remarkably, genetic regulation of lethargus quiescence is similar to genetic regulation of sleep in other animals. In particular, lethargus is regulated by a gene that is very similar to a gene regulating circadian sleep in other animals.
In addition to developmentally-timed sleep sleep, C. elegans also sleeps during the adult stage, after exposure to an environment that induces cellular stress. This stress-induced sleep requires just a single neuron, called the ALA neuron, which secretes neuropeptides including those encoded by the gene flp-13.
We have identified additional new sleep regulators in C. elegans and are currently studying how and in which cells these regulators function.
By studying the purpose and regulation of nematode sleep, we will identify additional novel sleep regulators, and gain insight into why sleep had evolved, a central biological mystery.
Rotation projects
Please see David about possible projects.
Description of Clinical Expertise
Sleep disorders: In particular disorders of sleep regulation and restless leg syndrome.