Molecular basis of behavior
circadian rhythms, sleep, genetics, metabolism, aging.
Description of Research
The laboratory is interested in the molecular basis of behavior. One major emphasis is on the mechanisms underlying circadian rhythms of behavior and physiology. Our accomplishments in this area have largely used a Drosophila model and include the isolation of the timeless clock gene, the finding that timeless (tim) functions in an autoregulatory loop that lies at the core of the endogenous clock, elucidating the mechanisms that synchronize the clock to light and discovering mechanisms that transmit signals from the clock and produce overt rest:activity rhythms. Ongoing work is addressing the mechanisms that generate a circadian period in the molecular clock, identifying the neural circuits that drive rhythms of rest:activity, and mapping the specific molecules/peptides that function in these circuits. We are also investigating circadian control of other physiological processes in Drosophila as well as mammals.
We also use Drosophila to investigate the homeostatic regulation of sleep. We and our collaborators developed a Drosophila model for sleep, which allows us to address longstanding questions about sleep regulation and function and has now been adopted worldwide. Using this model, we have conducted genetic screen to identify new sleep genes, dissected circuits that underlie sleep and also identified a function of sleep. We seek to understand the mechanisms that generate the need for sleep as well as those required to implement this need. We are also addressing the relevance of the circadian and sleep systems to other aspects of physiology, in particular to metabolism, and to healthy aging
Kayser Matthew S, Mainwaring Benjamin, Yue Zhifeng, Sehgal Amita: Sleep deprivation suppresses aggression in Drosophila. eLife 4: e07643, 2015.
Jang Christopher, Lahens Nicholas F, Hogenesch John B, Sehgal Amita: Ribosome profiling reveals an important role for translational control in circadian gene expression. Genome research 25(12): 1836-47, Dec 2015.
Weljie Aalim M, Meerlo Peter, Goel Namni, Sengupta Arjun, Kayser Matthew S, Abel Ted, Birnbaum Morris J, Dinges David F, Sehgal Amita: Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt. Proceedings of the National Academy of Sciences of the United States of America 112(8): 2569-74, Feb 2015.
Chen W-F, Maguire S, Sowcik M, Luo W, Koh K, Sehgal A: A neuron-glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants. Molecular psychiatry 20(2): 240-51, Feb 2015.
Cavanaugh Daniel J, Geratowski Jill D, Wooltorton Julian R A, Spaethling Jennifer M, Hector Clare E, Zheng Xiangzhong, Johnson Erik C, Eberwine James H, Sehgal Amita: Identification of a circadian output circuit for rest:activity rhythms in Drosophila. Cell 157(3): 689-701, Apr 2014.
Shi Mi, Yue Zhifeng, Kuryatov Alexandre, Lindstrom Jon M, Sehgal Amita: Identification of Redeye, a new sleep-regulating protein whose expression is modulated by sleep amount. eLife 3: e01473, 2014.
Kumar Shailesh, Chen Dechun, Jang Christopher, Nall Alexandra, Zheng Xiangzhong, Sehgal Amita: An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila. Nature communications 5: 5697, 2014.
Kayser Matthew S, Yue Zhifeng, Sehgal Amita: A critical period of sleep for development of courtship circuitry and behavior in Drosophila. Science (New York, N.Y.) 344(6181): 269-74, Apr 2014.
Kumar, S., Chen, D. and Sehgal, A. : “Dopamine acts through Cryptochrome to promote acute arousal in Drosophila”. Genes Dev. 26: 1224-1234, June 2012.
Sehgal, A, Mignot E.: "Genetics of sleep and sleep disorders". Cell 146(2): 194-207, July 2011.
Luo, W. and Sehgal, A. : "Regulation of circadian behavioral output via a MicroRNA-JAK/STAT circuit".
(featured on the cover of the Feb 17th issue) Cell 148(4): 765–779 February 2012.
back to top
Last updated: 01/12/2016
The Trustees of the University of Pennsylvania