PROJECT 4: MOLECULAR AND CELLULAR MECHANISMS FOR THERMAL ROBUSTNESS AND MULTISEN

温度强烈影响生理和行为，体温与体温有关 人类的动态平衡和疼痛，通过昆虫疾病媒介寻找宿主，以及所有动物的运动。 以黑腹隐翅虫为模型系统，我们提出了一种新的分子热传导途径。 涉及一类以前未被认识的潜在热感应蛋白的感应。因此，这项工作将 导致了一种新的热传感分子途径的定义，这对两者都具有潜在的广泛相关性 基础生物学和人类健康。 在初步实验中，我们已经确定了无感觉行为的一个关键调节因素。此外， 我们已经发现，这种蛋白质能够在异位时赋予神经元热敏感性。 表达。总而言之，我们的初步数据表明，这种蛋白质的功能可能是之前未被认识到的 热传感器的类型。 我们建议将这些研究扩展到三个目标。 1)我们将研究可能的热传感器在控制中的作用部位和分子性质 体温趋向性行为。 2)我们将研究这种假定的热传感器如何影响热敏神经元的温度感知。 3)我们将研究热传感器通过以下方式检测温度的分子机制 研究其潜在的信号机制和可能与之相互作用的信号通路 转换温度信息。 总之，这些研究将对热的分子机制提供新的基本见解。 轰动一时。 相关性(请参阅说明)： 这项提议研究了热感觉的分子机制。体温补偿对于 动物日照和生理学。在人类中，体温感应对疼痛、炎症和TX)死亡至关重要 温度调节。因此，热敏机制具有生物医学意义。此外, 温度感应对于疟疾和西方等人类疾病的昆虫媒介寻找宿主是重要的 尼罗河。因此，温度传感技术的研究对控制昆虫传播的人类疾病具有重要意义。

Temperature strongly affects physiology and behavior, and thermosensation is relevant to body temperature homeostasis and pain in humans, host seeking by insect disease vectors, and movement in all animals. Using D. melanogaster as a model system, we propose to define a novel molecular pathway for thermal sensing involving a previously unappreciated class of potential thermal sensing protein. This work will thus lead to the definition of a new molecular pathway for thermal sensing of potentially broad relevance for both basic biology and human health. In preliminary experiments, we have identified a critical regulator of themnosensory behavior. Furthermore, we have found that this protein is capable of conferring thermal sensitivity upon a neuron when ectopically expressed. Together our preliminary data suggest this protein may function as a previously unappreciated type of thermal sensor. We propose to extend these studies in three aims. 1) We will investigate the site of action and molecular nature ofthe putative thermal sensor in controlling thermotactic behavior. 2) We will examine how this putative thermal sensor affects temperature sensing by thermosensory neurons. 3) We will examine the molecular mechanisms by which the thermal sensor detects temperature by examining its potential signaling mechanism and the signaling pathways with which it may interact to transduce temperature infonnation. Together, these studies will provide fundamental new insights into the molecular mechanisms of thermal sensation. RELEVANCE (See instmctions): This proposal investigates the molecular mechanisms of thermal sensation. Thermosensation is critical for animal sun/ival and physiology. In humans, thermosensation is critical for pain, inflammation and tx)dy temperature regulation. Thus, thermosensory mechanisms are of biomedical relevance. In addition, themosensation is important for host-seeking by insect vectors of human diseases like malaria and West Nile. Thus the study of thermosensation is relevant to the control of insect-borne human disease.