The long-term research objective of this project is to characterize, in molecular terms, the circadian oscillator of Drosophila. Previous studies from this laboratory have shown that PER and TIM proteins interact in vivo and that this complex disassociates in response to light. They have also shown that the disruption of the cytoplasmic PER-TIM complex is associated with a delay in PER phosphorylation and PER nuclear entry.
The specific aims of this current application are to: (1) Characterize trans-acting factors and cis-acting elements that participate in the post-transcriptional control of per mRNA levels, (2) Determine the role of PER, TIM and dCLOCK phosphorylation and identify in vivo partners of PER and TIM, and (3) Characterize the spatial and temporal regulation of dCLOCK expression and determine how PER and TIM interact with the dCLOCK-CYC complex.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034958-06
Application #
6187285
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Kitt, Cheryl A
Project Start
1995-07-01
Project End
2003-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
6
Fiscal Year
2000
Total Cost
$326,056
Indirect Cost
Name
Rutgers University
Department
Type
Schools of Medicine
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Yildirim, Evrim; Chiu, Joanna C; Edery, Isaac (2015) Identification of Light-Sensitive Phosphorylation Sites on PERIOD That Regulate the Pace of Circadian Rhythms in Drosophila. Mol Cell Biol 36:855-70
Kwok, Rosanna S; Li, Ying H; Lei, Anna J et al. (2015) The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila. PLoS Genet 11:e1005307
Lee, Euna; Jeong, Eun Hee; Jeong, Hyun-Jeong et al. (2014) Phosphorylation of a central clock transcription factor is required for thermal but not photic entrainment. PLoS Genet 10:e1004545
Mahesh, Guruswamy; Jeong, EunHee; Ng, Fanny S et al. (2014) Phosphorylation of the transcription activator CLOCK regulates progression through a ? 24-h feedback loop to influence the circadian period in Drosophila. J Biol Chem 289:19681-93
Kim, Eun Young; Jeong, Eun Hee; Park, Sujin et al. (2012) A role for O-GlcNAcylation in setting circadian clock speed. Genes Dev 26:490-502
Chiu, Joanna C; Ko, Hyuk Wan; Edery, Isaac (2011) NEMO/NLK phosphorylates PERIOD to initiate a time-delay phosphorylation circuit that sets circadian clock speed. Cell 145:357-70
Edery, Isaac (2011) A master CLOCK hard at work brings rhythm to the transcriptome. Genes Dev 25:2321-6
Edery, Isaac (2011) A morning-induced, phosphorylation-gated repressor times evening gene expression: a new way for circadian clocks to use an old trick. Mol Cell 44:679-81
Ko, Hyuk Wan; Kim, Eun Young; Chiu, Joanna et al. (2010) A hierarchical phosphorylation cascade that regulates the timing of PERIOD nuclear entry reveals novel roles for proline-directed kinases and GSK-3beta/SGG in circadian clocks. J Neurosci 30:12664-75
Sun, Woo Chul; Jeong, Eun Hee; Jeong, Hyun-Jeong et al. (2010) Two distinct modes of PERIOD recruitment onto dCLOCK reveal a novel role for TIMELESS in circadian transcription. J Neurosci 30:14458-69

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