PROJECT 2: THE MOLECULAR AND CELLULAR BASIS OF THERMOSENSORY NAVIGATION IN DROSO

项目 2：DROSO 热传感导航的分子和细胞基础

• 批准号: 9274835
• 负责人: ARAVINTHAN D. SAMUEL
• 金额: $ 22.48万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274835
• 关键词: Adult; Affect; Animals; Behavior; Behavior Control; Biological Models; Biology; Body Temperature; Caenorhabditis elegans; Cations; Critical Pathways; Data; Detection; Disease; Disease Vectors; Drosophila genus; Esthesia; Family; Financial compensation; G-substrate; GTP-Binding Proteins; Genetic; Head; Health; Homeostasis; Human; Inflammation; Insect Control; Insect Vectors; Lead; Light; Malaria; Mammals; Mediating; Molecular; Movement; Nature; Neurons; Oocytes; Pain; Pathway interactions; Peripheral; Physiologic Thermoregulation; Physiological; Physiology; Protein Isoforms; Proteins; Rana; Regulation; Signal Pathway; Signal Transduction; Site; TRPA1 Channel; Temperature; Temperature Sense; Testing; The Sun; West Nile virus; Work; experimental study; fly; human disease; insect disease; insight; malaria transmission; novel; preference; receptor; response; sensor

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.

温度强烈影响生理和行为，热效率与体温有关 人类的体内平衡和疼痛，通过昆虫疾病向量寻求的宿主以及所有动物的运动。 使用D. melanogaster作为模型系统，我们建议定义一种新型的热途径 传感涉及先前未批准的潜在热感应蛋白。因此，这项工作将 导致定义一种新的分子途径，用于对两者的潜在广泛相关性的热感应 基本生物学和人类健康。 在初步实验中，我们已经确定了对效率行为的关键调节剂。此外， 我们发现，该蛋白能够在异位上赋予神经元的热敏感性 表达。我们的初步数据一起表明该蛋白质可能起到先前未欣赏的作用 热传感器的类型。 我们建议将这些研究扩展到三个目标。 1）我们将研究推定的热传感器的作用位点和分子性质 热功能行为。 2）我们将研究该推定的热传感器如何影响热感知神经元的温度传感。 3）我们将检查热传感器通过该机制检测到温度的分子机制 检查其潜在信号机制以及可能与之相互作用的信号通路 传递温度界。 总之，这些研究将为热的分子机制提供基本的新见解 感觉。 相关性（请参阅Instmctions）： 该建议研究了热感觉的分子机制。热能对 动物太阳/ival和生理学。在人类中，热敏度对于疼痛，炎症和TX）至关重要 温度调节。因此，热感应机制具有生物医学相关性。此外， 主敏对于通过疟疾和西部等人类疾病的昆虫向量寻求宿主很重要 尼罗河。因此，对热效率的研究与控制昆虫传播的人类疾病有关。