The two genes, period (per) and timeless (tim) are involved in the specification of circadian rhythms in the fruit-fly, Drosophila melanogaster. Previous work has shown that proteins encoded by these two genes associate physically, and the complex thus created is important in controlling several aspects of the clock that functions to maintain behavioral and developmental cycles. This proposal has five specific aims; they involve further characterization of the protein expression pattern of tim, and its relation to the expression of per; determination of the molecular basis of light sensitivity of Tim and the regulation of co-localization of Tim and Per in cultured cells. The two remaining specific aims pertain to the identification of other genes that may play a role in the generation of circadian rhythms. To this end, proteins identified through two-hybrid interactions with Per will be followed up, and a new gene, doubletime, which can be mutated to yield flies with short rhythms, will be further characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM054339-01A1
Application #
2023384
Study Section
Biological Sciences 2 (BIOL)
Project Start
1997-01-01
Project End
2000-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
1
Fiscal Year
1997
Total Cost
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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