Temperature entrainment of the molecular circadian clock circuits in Drosophila.

许多生物体依靠内部生物钟在最佳的日常时间表中组织其生物功能。生物钟功能的破坏与健康和福祉的负面结果有关，例如，与睡眠障碍、糖尿病、高血压和癌症有关。生物钟与温度有着矛盾的关系。一方面，它们采用所谓的温度补偿机制，在一定温度范围内可靠地保持每日时间，但另一方面，它们以惊人的灵敏度与每日温度周期同步。体温的日常节律本身是由大脑中的时钟控制的，被认为在保持不同组织中的时钟同步方面发挥着重要作用。果蝇黑腹果蝇是研究动物和人类用于日常计时的内部生物钟的一个极好的模型系统。虽然人们对生物钟维持这些复杂的温度反应的机制知之甚少，但果蝇的周期基因及其哺乳动物的对应基因被认为在日常时间保持、温度调节和温度补偿中起着关键作用。该项目的重点是最近发现的温度驱动诱导果蝇每个基因对温度同步和日常时间保持补偿的影响。参与这一过程的序列元件和转录因子将分别通过基因检测每个基因的不同片段以及不同的潜在调节因子来确定。接下来，该过程的功能重要性将通过描述由所需调节序列和转录复合物的遗传破坏引起的分子或行为昼夜节律的变化来定义。鉴于果蝇和哺乳动物per基因在结构和功能上的高度相似性，温度驱动的per基因表达在果蝇行为和分子节律调节中的作用的发现，也与理解人类和其他哺乳动物per基因表达对昼夜生理的影响有关。

Many organisms rely on internal circadian clocks to organize their biological functions in an optimal daily schedule. Disruption of circadian clock function has been associated with negative outcomes for health and well-being, for example, in relation to sleep disorders, diabetes, high blood pressure, and cancer. Circadian clocks have a paradoxical relationship with temperature. On one hand, they employ so-called temperature compensation mechanisms to reliably keep daily time over a range of temperatures, but on the other hand they synchronize to daily temperature cycles with remarkable sensitivity. Daily rhythms in body temperature, which are themselves controlled by a clock in the brain, are thought to play a major role in maintaining synchrony between the clocks in different tissues. The fruit fly Drosophila melanogaster is an excellent model system for studying the internal circadian clocks that animals and humans use for daily time keeping. While little is known about the mechanisms that allow circadian clocks to maintain these sophisticated temperature responses, the Drosophila period (per) gene and its mammalian counterparts are thought to play a key role in daily time keeping as well as temperature entrainment and temperature compensation. The proposed project focusses on the impact of the recently discovered temperature-driven induction of the Drosophila per gene on temperature synchronization and compensation of daily time keeping. The sequence elements and transcription factors involved in this process will be identified by genetically testing different segments of the per gene as well as different potential regulators, respectively. Next, the functional importance of this process will be defined by describing changes in molecular or behavioural circadian rhythms resulting from genetic disruption of the required regulatory sequences and transcription complexes. Given the high degree of structural and functional similarity between the per genes of flies and mammals, discoveries made for the role of temperature-driven per expression in the regulation of behavioural and molecular rhythms in flies are also relevant to understanding the impact of per expression in humans and other mammals on circadian physiology.