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
Kang, S Earl; Breton, Ghislain; Pruneda-Paz, Jose L (2018) Construction of Arabidopsis Transcription Factor ORFeome Collections and Identification of Protein-DNA Interactions by High-Throughput Yeast One-Hybrid Screens. Methods Mol Biol 1794:151-182
Li, Zheng; Bonaldi, Katia; Uribe, Francisco et al. (2018) A Localized Pseudomonas syringae Infection Triggers Systemic Clock Responses in Arabidopsis. Curr Biol 28:630-639.e4
Lee, Chin-Mei; Feke, Ann; Li, Man-Wah et al. (2018) Decoys Untangle Complicated Redundancy and Reveal Targets of Circadian Clock F-Box Proteins. Plant Physiol 177:1170-1186
Kubota, Akane; Ito, Shogo; Shim, Jae Sung et al. (2017) TCP4-dependent induction of CONSTANS transcription requires GIGANTEA in photoperiodic flowering in Arabidopsis. PLoS Genet 13:e1006856
Tripathi, Prateek; Carvallo, Marcela; Hamilton, Elizabeth E et al. (2017) Arabidopsis B-BOX32 interacts with CONSTANS-LIKE3 to regulate flowering. Proc Natl Acad Sci U S A 114:172-177
Tripathi, Prateek; Pruneda-Paz, José L; Kay, Steve A (2017) A Modified Yeast-one Hybrid System for Heteromeric Protein Complex-DNA Interaction Studies. J Vis Exp :
Shani, Eilon; Salehin, Mohammad; Zhang, Yuqin et al. (2017) Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors. Curr Biol 27:437-444
Breton, Ghislain; Kay, Steve A; Pruneda-Paz, José L (2016) Identification of Arabidopsis Transcriptional Regulators by Yeast One-Hybrid Screens Using a Transcription Factor ORFeome. Methods Mol Biol 1398:107-18
Huang, He; Alvarez, Sophie; Bindbeutel, Rebecca et al. (2016) Identification of Evening Complex Associated Proteins in Arabidopsis by Affinity Purification and Mass Spectrometry. Mol Cell Proteomics 15:201-17
Taylor-Teeples, M; Lin, L; de Lucas, M et al. (2015) An Arabidopsis gene regulatory network for secondary cell wall synthesis. Nature 517:571-5

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