Every day, most organisms are exposed to dramatic changes in the physical and ecological properties of their environment. They rely on circadian clocks to meet these challenges. These time-keeping mechanisms have a profound effect on behavior, physiology, gene expression and cell biochemistry. A fundamental property of circadian clocks is their self-sustained nature: they function even when an organism is exposed to constant conditions. However, circadian clocks only approximate day length, and therefore need to be reset every day to be beneficial. Light is arguably the most important input for circadian clocks. We therefore study in Drosophila the neuronal and molecular mechanisms underlying circadian photoreception. In the previous period of funding, we have identified novel circadian neurons and genes that modulate circadian behavior and photoresponses.
Our first aim will determine how specific groups of circadian neurons interact to synchronize circadian behavior with the light/dark cycle.
Our second aim will determine the function of the chromatin- remodeling factor KISMET in the modulation of circadian light responses.
Our third aim will study how the c- FOS homolog KAY influences circadian behavior and photoresponses. We anticipate that our work will identify general principles underlying the synchronization of circadian rhythms in animals. Indeed, it has recently been appreciated that in mammals also, synchronization of circadian rhythms depends both on cell-autonomous pathways resetting the molecular pacemaker and on interactions between circadian neurons. Our studies should therefore contribute to understand the biological bases of diseases and ailments associated with the dysfunction of circadian rhythms, such as those found in shift workers, and patients affected with specific sleep and mood disorders.

Public Health Relevance

Circadian clocks give an innate sense of time to most animals. These 24-hr period time-keeping mechanisms need to be reset daily to remain properly synchronized with the day/night cycle. Light is the most important environmental cue that can synchronize circadian clocks. We will therefore study the neuronal and molecular mechanisms underlying circadian photoreception in the model organism Drosophila melanogaster. The principles of circadian clock function and synchronization are remarkably similar in Drosophila and mammals. Our work may thus ultimately help understanding the biological bases of human diseases such as mood and sleep disorders, which are associated with the dysfunction and abnormal synchronization of circadian rhythms.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Biological Rhythms and Sleep Study Section (BRS)
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Sesma, Michael A
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University of Massachusetts Medical School Worcester
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Tataroglu, Ozgur; Zhao, Xiaohu; Busza, Ania et al. (2015) Calcium and SOL Protease Mediate Temperature Resetting of Circadian Clocks. Cell 163:1214-24
Tataroglu, Ozgur; Emery, Patrick (2015) The molecular ticks of the Drosophila circadian clock. Curr Opin Insect Sci 7:51-57
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Dubruille, Raphaelle; Murad, Alejandro; Rosbash, Michael et al. (2009) A constant light-genetic screen identifies KISMET as a regulator of circadian photoresponses. PLoS Genet 5:e1000787

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