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（由申请人提供）：拟除虫菊酯是从菊花提取物中提取的天然除虫菊的合成类似物，以其杀虫活性和对哺乳动物的低毒性而闻名。因此，它们被广泛用于控制多种节肢动物害虫，包括传播人类疾病的昆虫媒介。除了拟除虫菊酯的直接杀虫活性（基于其结合和过度激活昆虫神经系统中电压门控钠通道的能力）之外，天然存在的除虫菊酯和挥发性拟除虫菊酯还表现出明显的空间排斥性。事实上，空间 目前正在评估这些化合物对人类病媒控制的排斥性。然而，拟除虫菊酯空间排斥性的分子基础仍然难以捉摸。这项工作的中心假设是除虫菊和挥发性拟除虫菊酯通过与特定的嗅觉受体相互作用来发挥其空间驱避作用，而与它们基于钠通道的杀虫活性无关。这项新提案的具体目标是：1）鉴定果蝇中拟除虫菊酯响应的感觉器和嗅觉受体（OR）。 2) 蚊子中拟除虫菊酯响应感器和 OR 的鉴定。 3) 确定拟除虫菊酯响应性OR在空间排斥性中的作用。将结合电生理学和分子遗传学方法来检验这一假设，最终目标是鉴定负责拟除虫菊酯空间排斥性的嗅觉受体。拟议的研究具有创新性和开拓性，它开始阐明昆虫媒介对除虫菊酯和拟除虫菊酯的驱避性的分子基础。所获得的知识将为建立基于空间驱避性的替代昆虫媒介控制策略奠定基础，最终目标是提高拟除虫菊酯的效用并减少媒介昆虫传播疾病。