Our environment constantly affects our behavior. The circadian pacemaker is one of the best-characterized interfaces that connect complex behaviors with the environment. It helps most organisms to anticipate and adapt to the changes occurring every day in their surrounding. We are beginning to have a good sense of how these self-sustained rhythms function, but their synchronization is still poorly understood. This is a critical question, since improperly synchronized circadian rhythms would be of no use or even detrimental to the survival of an organism or to human health. Light input pathways have been recently studied in detail, but much less attention has been given to temperature input pathways, even though these inputs play a central role for circadian rhythm synchronization in many organisms. We propose to study temperature synchronization of the Drosophila pacemaker to answer three fundamental questions using a combination of genetic, molecular and behavioral approaches.
In aim 1 we will determine how temperature synchronizes circadian behavior and identify the neuronal structures necessary for this synchronization.
With aim 2 we will study genetically the mechanisms underlying the temperature input pathway.
In aim 3 we will determine how the circadian pacemaker responds to temperature cycle at a molecular level. Our work should reveal novel mechanisms underlying a fundamental property of circadian rhythms: their synchronization with the environment. This should ultimately result in a better understanding of the ailments associated with improper circadian rhythm synchronizations, such as jet lag, seasonal affective disorder, and desynchronization due to shift work.

Public Health Relevance

Circadian clocks time the physiology and behavior of most animals on a daily basis. We will study how temperature cycles synchronize the circadian clock of the model organism Drosophila to understand the general principles governing the synchronization of circadian rhythms with the day/night cycles. Since the mechanisms generating circadian rhythms are remarkably conserved in the animal kingdom, our work should ultimately contribute to the design of therapies aimed at alleviating ailments associated with abnormal synchronization of the human circadian clock, such as jet lag and mood disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM079182-03
Application #
7760191
Study Section
Special Emphasis Panel (ZRG1-NCF-D (09))
Program Officer
Tompkins, Laurie
Project Start
2008-04-01
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
3
Fiscal Year
2010
Total Cost
$321,750
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Biology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Tataroglu, Ozgur; Zhao, Xiaohu; Busza, Ania et al. (2015) Calcium and SOL Protease Mediate Temperature Resetting of Circadian Clocks. Cell 163:1214-1224
Tataroglu, Ozgur; Emery, Patrick (2014) Studying circadian rhythms in Drosophila melanogaster. Methods 68:140-50
Zhang, Yong; Emery, Patrick (2013) GW182 controls Drosophila circadian behavior and PDF-receptor signaling. Neuron 78:152-65
Karpowicz, Phillip; Zhang, Yong; Hogenesch, John B et al. (2013) The circadian clock gates the intestinal stem cell regenerative state. Cell Rep 3:996-1004
Zhang, Yong; Ling, Jinli; Yuan, Chunyan et al. (2013) A role for Drosophila ATX2 in activation of PER translation and circadian behavior. Science 340:879-82
Kaneko, Haruna; Head, Lauren M; Ling, Jinli et al. (2012) Circadian rhythm of temperature preference and its neural control in Drosophila. Curr Biol 22:1851-7
Zhang, Yong; Liu, Yixiao; Bilodeau-Wentworth, Diana et al. (2010) Light and temperature control the contribution of specific DN1 neurons to Drosophila circadian behavior. Curr Biol 20:600-5
Dubruille, Raphaelle; Emery, Patrick (2008) A plastic clock: how circadian rhythms respond to environmental cues in Drosophila. Mol Neurobiol 38:129-45