Molecular Mechanism of Pyrethroid Repellency in Drosophila Melanogaster and Mosquitoes

果蝇和蚊子拟除虫菊酯驱避作用的分子机制

• 批准号: 9125851
• 负责人: KE DONG
• 金额: $ 30.06万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-12 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9125851
• 关键词: Aedes; Anopheles gambiae; Arthropods; Attention; Basic Science; Beds; Behavioral Assay; Binding; CRISPR/Cas technology; Characteristics; Chemicals; Chemistry; Chrysanthemum; Culex (Genus); Culicidae; Dengue; Development; Disease Vectors; Drosophila genus; Drosophila melanogaster; Drug Metabolic Detoxication; Electrophysiology (science); Exhibits; Flowers; Foundations; Funding; Genes; Goals; Grant; Health; Housing; Individual; Insect Vectors; Insecta; Insecticides; Intervention; Knock-out; Knowledge; Logic; Malaria; Mammals; Mediating; Metabolic; Methods; Modeling; Molecular; Molecular Genetics; Mutation; Nervous system structure; Neurons; Olfactory Receptor Neurons; Process; Pyrethrum; Research; Resistance; Role; Smell Perception; Sodium Channel; System; Techniques; Testing; Time; Toxic effect; Vector-transmitted infectious disease; Work; Xenopus oocyte; analog; base; disease transmission; human disease; innovation; mutant; novel; olfactory receptor; pyrethroid; receptor; response; screening; vector; vector control; voltage

 DESCRIPTION (provided by applicant): Pyrethroids are synthetic analogues of naturally occurring pyrethrum from the flower extracts of Chrysanthemum and are best known for their insecticidal activity and low toxicity to mammals. As such, they are widely used in the control of numerous arthropod pests, including insect vectors that transmit human disease. Beside the direct insecticidal activity of pyrethroids which is based on their ability to bind and hyper- activate voltage-gated sodium channels in the insect nervous system, remarkably, natural-occurring pyrethrum and volatile pyrethroids exhibit clear spatial repellency. In fact, the spatial repellency of these compounds is now being evaluated for human disease vector control. However, the molecular basis of the spatial repellency of pyrethroid remains elusive. The central hypothesis of the proposed work is that pyrethrum and volatile pyrethroids exert their spatial repellency by interacting with specific olfactory receptors independent of their sodium channel-based insecticidal activity. The specific aims of this new proposal are: 1) Identification of pyrethroid-responsive sensilla and olfaction receptors (OR) in Drosophila melanogaster. 2) Identification of pyrethroid-responsive sensilla and ORs in mosquitoes. 3) Determination of the role of pyrethroid-responsive ORs in spatial repellency. A combination of electrophysiology and molecular genetic methods will be used to test the hypothesis, with the final goal of identificatio of olfactory receptors that are responsible for spatial repellency of pyrethroids. The proposed research is innovative and pioneering in beginning to elucidate the molecular basis of repellency of insect vectors to pyrethrum and pyrethroids. The knowledge gained will form the foundation on which to build alternative insect vector control strategies based on spatial repellency, with th ultimate goal of enhancing the utility of pyrethroids and reducing disease transmission by insect vectors.

 描述（由适用提供）：拟除虫菊酯是来自菊花的花卉提取物天然吡啶并以其绝缘活性和对哺乳动物毒性低的毒性而闻名的合成类似物。因此，它们被广泛用于控制众多节肢动物害虫，包括传播人类疾病的绝缘载体。除了拟除虫菊酯的直接绝缘活性外，它基于它们在绝缘神经系统中结合和过度激活电压门控钠通道的能力外，显着，天然存在的吡咯并肺炎和挥发性甲虫素暴露于明显的空间抑制。实际上，空间 现在，正在评估这些化合物的驱除性。然而，拟除虫菊酯的空间驱除的分子基础仍然难以捉摸。提出的工作的中心假设是，丙酸酯和挥发性拟除虫菊酯通过与特定的嗅觉受体相互作用而与其基于钠通道的杀虫活性无关。该新提案的具体目的是：1）果蝇中果蝇中拟甲虫素反应的感觉符号和嗅觉受体（OR）的鉴定。 2）在蚊子中鉴定拟除虫菊酯反应性感觉符号和ORS。 3）确定拟除虫菊酯反应性OR在空间驱除术中的作用。电生理学和分子遗传学方法的结合将用于检验假设，并最终鉴定了嗅觉受体，这些嗅觉受体负责拟甲虫素的空间抑制。拟议的研究具有创新性和开创性，以阐明绝缘载体对吡咯并拟甲虫素的分子基础。所获得的知识将构成基础，以基于空间驱除措施建立替代性绝缘载体控制策略，其最终目标是增强拟除虫菊酯的效用并通过绝缘载体来减少疾病传播。