Synchronization of Drosophila Circadian Rhythms by temperature cycles

描述（由申请人提供）：我们的环境不断影响着我们的行为。昼夜节律起搏器是将复杂行为与环境联系起来的最具特征的接口之一。它帮助大多数生物预测和适应周围每天发生的变化。我们开始很好地了解这些自我维持的节奏是如何运作的，但它们的同步性仍然知之甚少。这是一个关键问题，因为不适当的同步昼夜节律对生物体的生存或人类健康毫无用处，甚至有害。近年来，人们对光输入途径进行了详细的研究，但对温度输入途径的关注却很少，尽管这些输入在许多生物体的昼夜节律同步中起着核心作用。我们建议研究果蝇起搏器的温度同步，以回答三个基本问题，结合遗传学，分子和行为学的方法。在目标1中，我们将确定温度如何同步昼夜节律行为，并确定这种同步所必需的神经元结构。在目标2中，我们将研究温度输入途径的遗传机制。在目标3中，我们将确定昼夜节律起搏器如何在分子水平上响应温度周期。我们的工作应该揭示昼夜节律基本特性的新机制：它们与环境的同步。这将最终导致更好地理解与昼夜节律不正确同步相关的疾病，如时差、季节性情感障碍和轮班工作导致的不同步。

DESCRIPTION (provided by applicant): 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.