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界面之一。它帮助大多数生物体预测和适应周围环境每天发生的变化。我们开始对这些自我维持的节奏如何发挥作用有了很好的认识，但对它们的同步性仍然知之甚少。这是一个关键的问题，因为不适当地同步的昼夜节律对生物体的生存或人类健康毫无用处，甚至有害。光输入途径最近已被详细研究，但少得多的关注已给予温度输入途径，即使这些输入在许多生物体中的昼夜节律同步发挥核心作用。我们建议研究温度同步的果蝇起搏器回答三个基本问题，使用遗传，分子和行为的方法相结合。在目标1中，我们将确定温度如何影响昼夜节律行为，并确定这种同步所需的神经元结构。在目标2中，我们将从遗传学角度研究温度输入途径的机制。在目标3中，我们将在分子水平上确定昼夜节律起搏器如何响应温度循环。我们的工作应该揭示昼夜节律的一个基本特性的新机制：它们与环境的同步。这最终将导致更好地了解与不正确的昼夜节律同步相关的疾病，如时差，季节性情感障碍和轮班工作引起的去兴奋化。 公共卫生相关性：生物钟每天对大多数动物的生理和行为进行计时。我们将研究温度周期如何使模式生物果蝇的昼夜节律同步，以了解昼夜节律与昼夜周期同步的一般原理。由于产生昼夜节律的机制在动物王国中非常保守，我们的工作最终应该有助于设计旨在减轻与人类昼夜节律钟异常同步相关的疾病的治疗方法，例如时差和情绪障碍。

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.