Circadian Photoreception in Drosophila melanogaster

描述（由申请人提供）：每天，大多数生物都暴露在其环境的物理和生态特性的巨大变化中。他们依靠生物钟来应对这些挑战。这些计时机制对行为、生理、基因表达和细胞生化都有深远的影响。生物钟的一个基本特性是其自我维持的性质：即使生物体暴露在恒定的条件下，它们也能发挥作用。然而，生物钟只能近似于一天的长度，因此需要每天重置才能有益。光可以说是生物钟最重要的输入。因此，我们在果蝇中研究昼夜光接受的神经元和分子机制。在之前的资助期间，我们已经确定了调节昼夜节律行为和光反应的新型昼夜神经元和基因。我们的第一个目标是确定特定的昼夜神经元群如何相互作用，使昼夜节律行为与光/暗周期同步。我们的第二个目标是确定染色质重塑因子KISMET在调节昼夜节律光反应中的功能。我们的第三个目标是研究c- FOS同源物KAY如何影响昼夜行为和光反应。我们预计我们的工作将确定动物昼夜节律同步的一般原则。事实上，最近人们也认识到，在哺乳动物中，昼夜节律的同步既取决于重置分子起搏器的细胞自主通路，也取决于昼夜节律神经元之间的相互作用。因此，我们的研究应该有助于理解与昼夜节律功能障碍相关的疾病和疾病的生物学基础，例如在轮班工人和患有特定睡眠和情绪障碍的患者中发现的疾病和疾病。公共卫生相关性：生物钟赋予大多数动物一种天生的时间感。这些24小时周期的计时机制需要每天重置，以保持与昼夜周期的适当同步。光是能够同步生物钟的最重要的环境信号。因此，我们将研究模式生物黑腹果蝇昼夜节律光接受的神经元和分子机制。果蝇和哺乳动物的生物钟功能和同步原理非常相似。因此，我们的工作可能最终有助于理解人类疾病的生物学基础，如情绪和睡眠障碍，这些疾病与昼夜节律的功能障碍和异常同步有关。

DESCRIPTION (provided by applicant): 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.