Interdisciplinary Studies of Drosophila Rhythmic Behavior

我们之前的工作主要集中在果蝇昼夜节律的分子机制上。最初在果蝇中发现的基因的同源物现在已经与脊椎动物（包括鱼、青蛙、老鼠和人类）的节律行为和生理控制联系起来。在这里，我们对苍蝇的节奏行为进行了四类跨学科的研究。(1)我们将扩展经典的基因筛选（化学诱变），以寻找赋予异常活动/休息模式的突变。x染色体筛选产生了几个突变系，这些突变系对睡眠持续时间或睡眠阶段都有影响。在未来的工作中，我们将确定受影响基因的身份，及其表达的细胞和分子模式，并将在染色体2和3上开始可比筛选。我们将描述一种新的、睡眠减少的突变型失眠症。它们每天持续休息约400分钟，比野生型少近9小时。我们将确定失眠在大脑中的表达位置，表达失眠的细胞在组织睡眠中是否有其他作用，以及何时需要失眠功能来决定睡眠持续时间。(3)我们发现，当果蝇维持在一个光循环中时，周期mRNA会经历每日的聚腺苷化循环。多聚腺苷化的时间可因长时间暴露于光下而延迟。我们将确定这些反应是否为日长（季节）测量提供了一种新的机制。

Our prior work has focused on the molecular mechanisms underlying Drosophila¿s circadian rhythms. Orthologs of genes initially characterized in Drosophila have now been linked to the control of rhythmic behavior and physiology in vertebrates, including fish, frogs, mice and humans. Here we prose four classes of interdisciplinary investigations of the fly¿s rhythmic behavior. (1) We will extend a classical genetic screen (chemical mutagenesis) for mutations conferring aberrant activity/rest patterns. An X-chromosomal screen produced several mutant lines with effects on either sleep duration or phase. In future work, we will determine the identity of the affected genes, the cellular and molecular patterns of their expression, and will start a comparable screen on chromosomes 2 and 3. (2) We will characterize a novel, reduced- sleep mutant insomniac. These consistently rest for ~400 min/day, nearly 9 hours less than wild type. We will determine where insomniac is expressed within the brain, wheterh cells expressing insomniac have other roles in organizing sleep, and when insomniac function is required to determine sleep duration. (3) We have discovered that when Drosophila are maintained in a photocycle, period mRNA undergoes daily cycles of polyadenylation. The time of polyadenylation can be delayed by prolonged exposure to light. We will determine whether these responses provide a novel mechanism for day- length (seasonal) measurement.