The overall goal is to continue the analysis of the Drosophila circadian system using genetic and molecular approaches. The clock in Drosophila is known to be composed of a feedback loop generated through the coordinated action of clock genes- period (per), timeless (tim), Clock (Clk), cycle (cyc), double-time (dbt). All of these genes are conserved in mammals and function in similar, if not identical, ways to regulate mammalian circadian rhythms. This application seeks to determine the role of new genes/mutations recently isolated in the PI's laboratory and to isolate additional genes through microarray technology. In addition, a ds-RNA-based method will be used to reduce activity of clock and putative clock genes in a tissue-specific manner.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054339-06
Application #
6490099
Study Section
Genetics Study Section (GEN)
Program Officer
Tompkins, Laurie
Project Start
1997-01-01
Project End
2004-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
6
Fiscal Year
2002
Total Cost
$375,750
Indirect Cost
Name
Rockefeller University
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Lin, Changfan; Top, Deniz; Manahan, Craig C et al. (2018) Circadian clock activity of cryptochrome relies on tryptophan-mediated photoreduction. Proc Natl Acad Sci U S A 115:3822-3827
Ganguly, Abir; Manahan, Craig C; Top, Deniz et al. (2016) Changes in active site histidine hydrogen bonding trigger cryptochrome activation. Proc Natl Acad Sci U S A 113:10073-8
Top, Deniz; Harms, Emily; Syed, Sheyum et al. (2016) GSK-3 and CK2 Kinases Converge on Timeless to Regulate the Master Clock. Cell Rep 16:357-367
Axelrod, Sofia; Saez, Lino; Young, Michael W (2015) Studying circadian rhythm and sleep using genetic screens in Drosophila. Methods Enzymol 551:3-27
Kidd, Philip B; Young, Michael W; Siggia, Eric D (2015) Temperature compensation and temperature sensation in the circadian clock. Proc Natl Acad Sci U S A 112:E6284-92
Jang, A Reum; Moravcevic, Katarina; Saez, Lino et al. (2015) Drosophila TIM binds importin ?1, and acts as an adapter to transport PER to the nucleus. PLoS Genet 11:e1004974
Crane, Brian R; Young, Michael W (2014) Interactive features of proteins composing eukaryotic circadian clocks. Annu Rev Biochem 83:191-219
Vaidya, Anand T; Top, Deniz; Manahan, Craig C et al. (2013) Flavin reduction activates Drosophila cryptochrome. Proc Natl Acad Sci U S A 110:20455-60
Rogulja, Dragana; Young, Michael W (2012) Control of sleep by cyclin A and its regulator. Science 335:1617-21
Syed, Sheyum; Saez, Lino; Young, Michael W (2011) Kinetics of doubletime kinase-dependent degradation of the Drosophila period protein. J Biol Chem 286:27654-62

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