Molecular genetics of thermotaxis

趋热性的分子遗传学

• 批准号: 7901921
• 负责人: CRAIG MONTELL
• 金额: $ 27.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-31 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901921
• 关键词: Accounting; Adult; Affect; Anopheles gambiae; Behavior; Biochemical; Biochemistry; Cells; Cellular biology; Chemicals; Data; Dengue; Diptera; Discrimination; Disease; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Esthesia; Gene Proteins; Genes; Genetic; Goals; Health; Heating; Homologous Gene; Human; Incidence; Insect Repellents; Insecta; Invertebrates; Larva; Lead; Life; Malaria; Mammals; Medical; Molecular; Molecular Biology; Molecular Genetics; Molecular Target; Mosquito-borne infectious disease; Movement; Mutation; Neurons; Noise; Organism; Painless; Proteins; Reporting; Research; Research Proposals; Rhodopsin; Signal Pathway; Signaling Protein; Site; Staging; TRP channel; TRPA channel; TRPV channel; Temperature; Testing; West Nile virus; Yellow Fever; base; drug efficacy; efficacy testing; fly; genome wide association study; improved; insight; interdisciplinary approach; protein function; public health relevance; research study; response; stem; vector; warm temperature

DESCRIPTION (provided by applicant): The goal of our proposed research is to understand the molecular mechanisms underlying thermotaxis in the fruitfly, Drosophila melanogaster. Thermotaxis, which is the movement towards a preferred temperature, has been studied in a wide range of vertebrate and invertebrate organisms. However, only a few of the genes and proteins required for temperature discrimination are known. There are two rationales for the proposed research. First, thermotaxis in insects has potential medical relevance, as the host-seeking behaviors of disease spreading vectors, such as the malaria-spreading insect, Anopheles gambiae, appear to involve temperature sensation. Thus, identification of the proteins essential for this behavior may lead to approaches to interfere with it. Drosophila homologs of TRP channels, which are thermosensors in mammals, also function in thermotaxis. Since several thermoTRPs in mammals are also regulated by aversive chemicals, we propose that Drosophila thermoTRPs may be targets for insect repellents. The discovery of the molecular targets for repellents has medical implications, given that mosquito-borne disease is a worldwide health problem. Second, the observations that TRPs are themosensors in flies and mammals raise the possibility that other proteins that function in thermosensation may be shared. Thus, identification of genes and proteins that function in Drosophila thermotaxis may provide new insights into mammalian thermosensation. To characterize thermotaxis and thermoTRPs, we propose to use a multidisciplinary approach, using a combination of genetics, biochemistry, cell biology, molecular biology and electrophysiology. The specific aims of the current proposal are to: 1) test the hypothesis that a TRP channel (Painless) functions in thermotaxis in adult flies, 2) test the hypothesis that thermoTRPs are targets for insect repellents, 3) test the hypothesis that the TRPV channels (Nanchung and Inactive) operate in combination for larval thermotaxis, and 4) test the hypothesis that rhodopsins function in a thermotaxis signaling pathway. This last aim is concerned with testing the proposal that rhodopsins are direct thermosensors, which may account for the long-known phenomenon that dark-noise and spontaneous activation of rhodopsin is temperature sensitive. A long-term goal of the proposed research is to apply the insights on Drosophila thermoTRPs to identify improved insect repellents and to test the efficacies of drugs that inhibit thermally-driven thermotaxis behaviors that could be applied to medically important Diptera. PUBLIC HEALTH RELEVANCE: The proposed research is concerned with identifying the genes and proteins that are important for thermotaxis and the responses to insect repellents, in the fruitfly. A long-term goal of the proposed research is to apply the insights on fruitfly to identify improved insect repellents and to test the efficacies of drugs that inhibit thermally-driven thermotaxis behaviors that could be applied to medically important insects, such as those that spread malaria and West Nile Virus.

描述（由申请人提供）：我们拟议的研究的目的是了解果蝇果蝇果蝇中的果蝇中的分子机制。热Xt型是向优选温度的运动，已经在脊椎动物和无脊椎动物生物范围内进行了研究。但是，仅知道温度歧视所需的少数基因和蛋白质。拟议的研究有两个理由。首先，昆虫中的热门症具有潜在的医学相关性，因为疾病传播媒介的寻求宿主的行为，例如膨胀疟疾的昆虫，Anopheles gambiae，似乎涉及温度感觉。因此，对这种行为必不可少的蛋白质的识别可能会导致干扰它的方法。 TRP通道的果蝇同源物（哺乳动物中的热传感器）也起作用。由于哺乳动物中的几个ThermotRP也受厌恶化学物质的调节，因此我们建议果蝇ThermotRP可能是昆虫驱虫剂的靶标。鉴于蚊子传播的疾病是全球健康问题，发现驱虫剂的分子靶标具有医学意义。其次，观察到TRP是果蝇和哺乳动物中的传感器的观察结果，提出了可以共享其他功能中其他功能的蛋白质的可能性。因此，鉴定在果蝇热持蛋白质中起作用的基因和蛋白质可能会为哺乳动物热增强提供新的见解。为了表征热门和助剂，我们建议使用遗传学，生物化学，细胞生物学，分子生物学和电生理学的组合使用多学科方法。 The specific aims of the current proposal are to: 1) test the hypothesis that a TRP channel (Painless) functions in thermotaxis in adult flies, 2) test the hypothesis that thermoTRPs are targets for insect repellents, 3) test the hypothesis that the TRPV channels (Nanchung and Inactive) operate in combination for larval thermotaxis, and 4) test the hypothesis that rhodopsins function in a thermotaxis信号通路。最后一个目的是测试视紫红蛋白是直接热传感器的建议，这可能解释了众所周知的现象，即黑诺伊斯和自发激活Rhodopsin对温度敏感。拟议的研究的一个长期目标是应用对果蝇ThermotRP的见解，以鉴定改进的驱虫剂，并测试抑制可以应用于医学上重要双翅目的热驱动热驱动行为的药物的效率。公共卫生相关性：拟议的研究涉及识别果蝇中对热门抗体和对昆虫驱虫剂的反应至关重要的基因和蛋白质。拟议的研究的一个长期目标是应用对果蝇的见解，以鉴定驱虫剂的改善，并测试抑制热驱动的热持续行为的药物的疗效，这些行为可以应用于医学上重要的昆虫，例如传播疟疾和西尼罗河病毒的昆虫。