The long-term goal of this proposal is to understand how circadian clocks function within eukaryotic cells. The purpose of a circadian clock is to regulate cellular processes such that they occur at specific times of the day and night. Circadian clocks are found in all kingdoms of life and the presence of a functional circadian clock has been shown to confer enhanced fitness onto the organism. Forward genetic approaches to understanding clock function have been instrumental in numerous model organisms including Arabidopsis and our initial gene discovery program yielded a key clock gene, TOC1, and the founding member of a novel photoreceptor family, ZTL. The success of this gene discovery program validates the approach, although currently circadian screens in Arabdopsis are not saturated since we are still identifying novel clock genes. We will continue the characterization of existing mutants and isolate novel mutants by developing new reporters based on TOC1, a critical component identified from our previous screens. In addition, we will exploit reverse genetic approaches to explore hypotheses about the role of clock gene family members in the circadian clock. Given the ubiquity of circadian-regulated physiology, the identification of common clock components will have an impact on understanding the pacemaker mechanism and malfunctions associated with known features of human well- being. 7. Project Narrative: Almost all organisms possess circadian clocks that control daily rhythms in physiology, metabolism and behavior. The molecular architecture of these clocks appears similar amongst all organisms. Thus the advances learned in model systems such as Arabidopsis will be broadly applicable to understanding rhythms in humans and the known pathologies associated with their dysfunction in a wide range of diseases.

Public Health Relevance

Almost all organisms possess circadian clocks that control daily rhythms in physiology; metabolism andbehavior. The molecular architecture of these clocks appears similar amongst all organisms. Thus theadvances learned in model systems such as Arabidopsis will be broadly applicable to understandingrhythms in humans and the known pathologies associated with their dysfunction in a wide range ofdiseases to impact the treatment of human circadian disorders such as diabetes; SAD; insomnia and jet-lag.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056006-16
Application #
8197415
Study Section
Special Emphasis Panel (ZRG1-NCF-D (09))
Program Officer
Hagan, Ann A
Project Start
1996-09-01
Project End
2012-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
16
Fiscal Year
2012
Total Cost
$334,313
Indirect Cost
$117,929
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Gendron, Joshua M; Pruneda-Paz, Jose L; Doherty, Colleen J et al. (2012) Arabidopsis circadian clock protein, TOC1, is a DNA-binding transcription factor. Proc Natl Acad Sci U S A 109:3167-72
Li, Lin; Ljung, Karin; Breton, Ghislain et al. (2012) Linking photoreceptor excitation to changes in plant architecture. Genes Dev 26:785-90

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