Seasonal Adaptation of a Circadian Clock

描述(由申请人提供)：本提案的总体目标是 了解生物钟(或起搏器)如何适应新的相位 对环境温度和日长季节性变化的响应路线 (光周期)，一个很少受到分子关注的话题 透视。生物钟的这一特征具有巨大的生物学意义 重大意义，因为它使生物体能够(1)采用最佳的相位对齐 在生理和行为节律和流行的环境之间 条件，以及(2)触发季节性适当的反应。一位少校 本申请中提出的具体目标的基础是基于我们的 最近发表的研究[Majercak等人，(1999)神经元，24：219]表明 黑腹果蝇3-末端内含子的温敏剪接 周期(Dper)RNA(这里称为dmpi8；D.Blackogaster dper内含子8) 为该物种在白天的优先活动做出了重大贡献 在季节性寒冷的日子里。最近的发现表明，尽管剪接 Dmpi8的效率受到低温的刺激，光则抑制这一作用。 拼接活动，展示错综复杂的多模式监管。我们的发现 提示dmpi8剪接的热和光周期调节作用如下 向动物传递日历信息的“季节性传感器”。在这 应用我们提出的方法来确定温度和光线如何共同调节 Dmpi8的剪接效率。这些研究不仅会调查一部小说 光对黑腹毛虫生物钟的影响但我们最近的发现 暗示了视觉信号转导级联在该阶段的新作用 控制大脑深层起搏细胞驱动的活动节律。此外， 我们将分析几种果蝇的生物钟和行为节律 来自广泛纬度梯度的物种。这些研究可能会揭示 自然选择在生物钟适应中的作用 季节性气候的地理变化。为了实现这些目标，我们 建议采取包括体外在内的多因素实验策略 生化、组织培养和全动物方法。随着最近的 认识到生物钟背后的基本分子逻辑来自 各种各样的生物体，包括人类，都是保守的，这是预期的 尽管具体细节会与我们对昼夜节律的调查不同 时钟集成了多种环境形态，将导致一般 适用于多种生物节律系统的原理。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to understand how a circadian clock (or pacemaker) accommodates new phase alignments in response to seasonal changes in ambient temperature and daylength (photoperiod), a topic that has received little attention from a molecular perspective. This feature of circadian clocks has immense biological significance because it enables organisms to (1) adopt optimal phase-alignments between physiological and behavioral rhythms and the prevailing environmental conditions, and (2) trigger seasonally appropriate responses. A major foundation for the proposed specific aims in this application is based on our recent published work [Majercak et al., (1999) Neuron, 24:219] showing that the thermosensitive splicing of the 3-terminal intron from the D. melanogaster period (dper) RNA (herein refereed to as dmpi8; D. melanogaster dper intron 8) makes a major contribution to the preferential daytime activity of this species during seasonally cold days. Recent findings indicate that whereas the splicing efficiency of dmpi8 is stimulated by cold temperatures, light inhibits this splicing event, demonstrating intricate multi-modal regulation. Our findings suggest that the thermal and photoperiodic regulation of dmpi8 splicing acts as a "seasonal sensor" conveying calendar information to the animal. In this application we propose to determine how temperature and light co-regulate the splicing efficiency of dmpi8. No only will these studies investigate a novel effect of light on the D. melanogaster circadian clock but our recent findings implicate a new role for the visual signal transduction cascade in the phase control of activity rhythms driven from deep brain pacemaker cells. Moreover, we will analyze the clockworks and behavioral rhythms in several Drosophila species from a wide range of latitudinal gradients. These studies might reveal a role for natural selection in the adaptation of circadian clocks to geographical variations in seasonal climates. To accomplish these goals we propose to take multifacted experimental strategies including in vitro biochemical, tissue culture and whole animal approaches. With the recent realization that the basic molecular logic underlying circadian clocks from a wide variety of organisms, including humans, is conserved, it is anticipated that although specific details will differ our investigation of how a circadian clock integrates multiple environmental modalities will lead to general principles that are applicable to a wide range of circadian systems.