Circadian rhythms are endogenous rhythms that help keep organisms in synchrony with their environment and contribute to an organism's fitness for life on earth. The importance of circadian rhythms has been shown for many different health issues, from the timing of cancer treatments (Gorbacheva et al., 2005) to obesity and metabolic syndrome (Turek et al., 2005). Understanding the molecular basis of these rhythms will help us find ways to affect the processes they regulate in humans. Our long term goal is to understand in detail how the circadian clock functions in the model system Arabidopsis, and how both transcriptional and post-transcriptional processes are used to give this endogenous timekeeper a period of about a day in constant conditions of light and temperature. We will focus particularly on the putative central oscillator component CCA1 and extend our studies with CCA1 to other putative components such as LHY. Our specific experimental aims are: 1. To understand how CCA1 and LHY function in generating circadian rhythms, a. To test whether they (and other proposed components) are truly central oscillator components by testing whether a pulse of the protein can reset the phase of circadian rhythms, b. To test what allows rhythms to continue for a short time when CCA1 is absent and LHY is reduced and whether a line that is completely null for both CCA1 and LHY stops all rhythms immediately, c. To understand how the transcription of CCA1 is regulated, d. To identify the genome wide targets of CCA1 and LHY. 2. To understand the roles of post-transcriptional processes in maintaining circadian rhythms, a. To understand the roles that phosphorylation of CCA1 and LHY, particularly by the protein kinase CK2, plays in their functions, b. To understand how degradation of the CCA1 and LHY proteins (which themselves cycle with a circadian rhythm) is regulated, c. To see whether CCA1-LHY protein interactions and localization dynamics in the cell play a role in circadian regulation. 3. To identify and characterize additional genes/proteins that are involved with the circadian clock, a. To understand the role of our recently discovered CCA1-interacting protein (designated CIRP), which affects the period of circadian rhythms, b. To investigate the possible significance of CCA1 interaction with histone H3. c. To identify the genes corresponding to the mutants that we have isolated that have altered circadian rhythms and to develop an understanding of the roles of these genes.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-NCF-D (09))
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Tompkins, Laurie
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University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
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Liu, Hongtao; Wang, Qin; Liu, Yawen et al. (2013) Arabidopsis CRY2 and ZTL mediate blue-light regulation of the transcription factor CIB1 by distinct mechanisms. Proc Natl Acad Sci U S A 110:17582-7
Lu, Sheen X; Webb, Candace J; Knowles, Stephen M et al. (2012) CCA1 and ELF3 Interact in the control of hypocotyl length and flowering time in Arabidopsis. Plant Physiol 158:1079-88
Lu, Sheen X; Liu, Hongtao; Knowles, Stephen M et al. (2011) A role for protein kinase casein kinase2 *-subunits in the Arabidopsis circadian clock. Plant Physiol 157:1537-45
Lu, Sheen X; Knowles, Stephen M; Webb, Candace J et al. (2011) The Jumonji C domain-containing protein JMJ30 regulates period length in the Arabidopsis circadian clock. Plant Physiol 155:906-15
Bu, Qingyun; Zhu, Ling; Dennis, Michael D et al. (2011) Phosphorylation by CK2 enhances the rapid light-induced degradation of phytochrome interacting factor 1 in Arabidopsis. J Biol Chem 286:12066-74
Lu, Sheen X; Tobin, Elaine M (2011) Chromatin remodeling and the circadian clock: Jumonji C-domain containing proteins. Plant Signal Behav 6:810-4
Lu, Sheen X; Knowles, Stephen M; Andronis, Christos et al. (2009) CIRCADIAN CLOCK ASSOCIATED1 and LATE ELONGATED HYPOCOTYL function synergistically in the circadian clock of Arabidopsis. Plant Physiol 150:834-43
Gardner, Gary; Lin, Chentao; Tobin, Elaine M et al. (2009) Photobiological properties of the inhibition of etiolated Arabidopsis seedling growth by ultraviolet-B irradiation. Plant Cell Environ 32:1573-83
Andronis, Christos; Barak, Simon; Knowles, Stephen M et al. (2008) The clock protein CCA1 and the bZIP transcription factor HY5 physically interact to regulate gene expression in Arabidopsis. Mol Plant 1:58-67
Knowles, Stephen M; Lu, Sheen X; Tobin, Elaine M (2008) Testing time: can ethanol-induced pulses of proposed oscillator components phase shift rhythms in Arabidopsis? J Biol Rhythms 23:463-71

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