Impeding our understanding of behaviorally quiescent states such as sleep and their relationship to development is a lack of an animal model that has a well-understood anatomy in addition to powerful tools for genetic analysis of quiescence. Caenorhabditis elegans is a genetically tractable animal with an exquisitely well-understood neuroanatomy and has been used to model several processes of human disease relevance. A quiescent state occurs during lethargus, a developmentally controlled period during which there is extensive synaptogenesis in the nervous system. Dr. Raizen, the principal investigator, plans to investigate the processes and neurochemicals that control the timing and execution of this quiescent state. Specifically, he will test the roles of serotonin, dopamine, and adenosine in the control of quiescence and characterize the homeostatic control of this state.
In Aim 2, he will test the hypothesis that the LIN-42 protein, the C. elegans orthologue to the circadian protein PERIOD, plays a role in the control of the timing of quiescence.
In Aim 3, he will determine whether or not quiescence is required for synaptogenesis during development. These studies will compare and contrast behavioral quiescence in C. elegans to that seen in other animals and will answer the question: Can quiescence in C. elegans be considered a sleep like state? Regardless of the answer, the study will address fundamental problems in behavioral state control and its relationship to nervous system change. The studies will be performed in the laboratories of Dr. Allan Pack in the Center for Sleep and Neurobiology, and of Dr. Meera Sundaram, in the Department of Genetics. This training grant will support Dr. Raizen while he learns the scientific field of sleep and chronobiology and develops C. elegans as a model system for the study of behavioral quiescence and its relationship to development.
| You, Young-jai; Kim, Jeongho; Raizen, David M et al. (2008) Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in C. elegans: a model for satiety. Cell Metab 7:249-57 |
| Zimmerman, John E; Naidoo, Nirinjini; Raizen, David M et al. (2008) Conservation of sleep: insights from non-mammalian model systems. Trends Neurosci 31:371-6 |
| Zimmerman, John E; Raizen, David M; Maycock, Matthew H et al. (2008) A video method to study Drosophila sleep. Sleep 31:1587-98 |
| Raizen, David M; Mason, Thornton B A; Pack, Allan I (2006) Genetic basis for sleep regulation and sleep disorders. Semin Neurol 26:467-83 |
| Raizen, David M; Cullison, Kevin M; Pack, Allan I et al. (2006) A novel gain-of-function mutant of the cyclic GMP-dependent protein kinase egl-4 affects multiple physiological processes in Caenorhabditis elegans. Genetics 173:177-87 |
