Organization of the circadian clock and its interaction with the cellular environment
Keywords: Drosophila, circadian clock, metabolism, redox, aging, light entrainment
Circadian behavior is driven by an endogenous molecular oscillator and its output signals. In the fruit fly Drosophila melanogaster, the core molecular circadian clock consists of four major components: CLK, CYC, PER and TIM. Rhythmic inhibition of CLK-CYC transcriptional activity by the temporal expression of PER-TIM complex generates rhythmic gene transcriptions. It's still largely unknown as how this core oscillator regulates fundamental physiological processes, such as sleep and energy metabolism, and how it integrates cellular conditions to influence circadian output.
My research focuses on the determination of mechanisms underlying circadian regulation of energy metabolism, and identification of cellular/environmental conditions that feed into the circadian clock circuitry, during normal aging and also under stressful conditions.
Zheng X, Sowcik M, Chen D, Sehgal A: Casein kinase 1 promotes synchrony of the circadian clock network. Molecular & Cellular Biology in press, June 2014.
Cavanaugh DJ, Geratowski JD, Wooltorton JRA, Singh JM, Hector CE, Zheng X, Johnson EC, Eberwine JH, Sehgal A: Identification of a circadian output circuit for rest:activity rhythms in Drosophila. Cell. Cell Press, 157(3): 689-701, April 2014.
Luo W, Chen WF, Yue Z, Chen D, Sowcik M, Sehgal A, Zheng X: Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations. Aging Cell 11(3): 428-38, Jun 2012 Notes: Corresponding author.
Zheng X, Sehgal A: AKT and TOR Signaling Set the Pace of the Circadian Pacemaker. Current Biology 20(13): 1203-1208, Jul 2010.
Zheng X*, Koh K*, Sowcik M, Smith CJ, Chen D, Wu MN, Sehgal A
: An isoform-specific mutant reveals a role of PDP1ε in the circadian oscillator. Journal of Neuroscience 29(35): 10920-10927, Sep 2009 Notes: *co-first author.
Xu K, Zheng X, Sehgal A: Regulation of Feeding and Metabolism by Neuronal
and Peripheral Clocks in Drosophila. Cell Metabolism 8(4): 289-300, Oct 2008.
Sathyanarayanan S*, Zheng X*, Kumar S, Chen C-H, Chen D, Hay B, and Sehgal A: Identification of novel genes involved in light-dependent CRY degradation through a genome-wide RNAi screen.
Genes & Development 22(11): 1522-1533, Jun 2008 Notes: *Co-first author.
Zheng X, Yang Z, Yue Z, Alvarez JD, Sehgal A: FOXO and insulin signaling regulate the sensitivity of circadian clock to oxidative stress. Proc Natl Acad Sci USA 104(40): 15899-904, Oct 2007.
Koh K, Zheng X, Sehgal A : JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS. Science 23(312 ): 1809-12, Jun 2006.
Sathyanarayanan S, Zheng X, Xiao R, Sehgal A: Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A. Cell 116: 603-615, Feb 2004.
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Last updated: 07/15/2014
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