Opsins and TRP channels controlling sensation and behavior in Aedes aeygpti

视蛋白和 TRP 通道控制白纹伊蚊的感觉和行为

• 批准号: 10676854
• 负责人: CRAIG MONTELL
• 金额: $ 54.26万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676854
• 关键词: Address; Aedes; Agriculture; Animals; Auditory; Behavior; Behavior Control; Behavioral; Behavioral Assay; Biological; Biological Assay; Blood; Bypass; Carbon Dioxide; Cells; Ceratitis capitata; Chemicals; Computer software; Consumption; Convection; Cues; Culicidae; Dangerousness; Data; Dengue; Detection; Development; Devices; Disease; Disease Vectors; Drosophila genus; Electrophysiology (science); Elements; Environment; Esthesia; Family; Female; G-Protein-Coupled Receptors; Genetic; Glean; Goals; Hearing; Homing; Human; Infrared Rays; Insect Repellents; Insecta; Light; Male Sterility; Male Sterilizations; Mediating; Modeling; Molecular Genetics; Monitor; Mosquito Control; Mosquito-borne infectious disease; Mutate; Mutation; Neurons; Odors; Opsin; Partner in relationship; Persons; Population; Population Control; Protein Isoforms; Proteins; Research; Rhodopsin; Role; Sensory; Sensory Receptors; Series; Signaling Protein; Skin; Smell Perception; Sterility; Stimulus; TRP channel; TRPA channel; Taste Perception; Techniques; Testing; Transgenic Organisms; Virus; Visual; Vitamin A; Work; Yellow Fever; ZIKA; deaf; design; egg; experimental study; genetic approach; genetic element; improved; in vivo; innovation; insight; male; member; multimodality; olfactory receptor; prevent; receptor; sensor; sex; sterile insect technique; success; tool; viral transmission

Abstract The mosquito Aedes aegypti spreads diseases such as dengue, Zika, yellow fever, and others that afflict >100 million people each year. These mosquitoes rely on multiple keen senses to locate human hosts for blood meals, and for finding conspecifics for mating. Currently, we have only a rudimentary understanding of the receptors that control these critical behaviors. The goal of the proposed research is to address this gap. The unifying theme of this proposal is to test the idea that opsins and TRP channels are two key classes of signaling proteins that have broad roles in sensation and in controlling behavior in Ae. aegypti. Rhodopsins are the founding G-protein coupled receptors (GPCRs). We recently discovered that opsins are multi-modal sensory receptors, challenging 100 years of dogma that they detect only light. To find humans, female Ae. aegypti integrate information from diverse stimuli, including CO2, visual cues, organic molecules, and convection heat from skin. We discovered another cue. Aim 1 builds on our preliminary data that Ae. aegypti use infrared (IR) radiation as an additional host stimulus. We outline experiments to reveal the roles of opsins and the TRPA1 channel in IR detection. We propose to identify the IR-sensing neurons that express the opsins and TRPA1, and to test a model to explain the role of opsins in IR sensation. To pursue this aim, we devised a highly effective assay for monitoring IR attraction and a new molecular genetic approach to bypass difficulties in combining multiple genetic elements. Aim 2 takes advantage of a mutation that we created in another TRP (TRPV-A), which renders males and females deaf. We will test the roles of hearing and TRPV-A in swarm formation, in mating, and in finding humans. Aim 2 will also build on the observations that male mating requires audition mediated by TRPV-A to devise a strategy to overcome a major impediment limiting the efficacy of the sterile insect technique (SIT). SIT is a promising strategy to suppress Ae. aegypti. It involves inundating a local population with sterile males, which then render females sterile upon mating. An obstacle to using SIT is that wild-type males outcompete sterile males. We propose that manipulation of the activity of the TRPV-A- expressing auditory neurons elevates sterile male mating success, and will thereby increase the efficacy of SIT in suppressing Ae. aegypti. Aim 3 concerns identifying the sensory receptors for repellents. We propose to test the idea that an opsin functions as a highly sensitive receptor for insect repellents. If confirmed by the proposed experiments, this would demonstrate that opsins comprise a new class of olfactory receptor. To accomplish our goals, we have developed an extensive repertoire of state-of-the-art approaches. These include new molecular genetic tools, a suite of behavioral assays, original video tracking software, and in vivo electrophysiological recordings. In summary, this project will reveal the roles of opsins and TRP channels in allowing mosquitoes to sense humans and conspecific mates. The insights gleaned from this work have exciting potential to lead to innovative strategies to control Ae. aegypti and reduce insect-borne disease.

抽象的 蚊子埃及埃及传播了登革热，寨卡，黄热病等疾病 每年有百万人。这些蚊子依靠多种敏感的感官来定位人类的宿主 用餐，并用于寻找交配的特异性。目前，我们对 控制这些关键行为的受体。拟议的研究的目的是解决这一差距。这 该建议的统一主题是测试Opsins和TRP频道是两个关键类别的想法 在感觉和控制AE中具有广泛作用的信号蛋白。埃及。视紫红蛋白是 建立的G蛋白偶联受体（GPCR）。我们最近发现Opsin是多模式的 感觉受体，挑战100年的教条，它们仅检测到光。寻找人类，女性AE。 埃及整合来自不同刺激的信息，包括二氧化碳，视觉提示，有机分子和 对流的皮肤热量。我们发现了另一个提示。 AIM 1建立在我们AE的初步数据的基础上。埃及 使用红外（IR）辐射作为额外的宿主刺激。我们概述了实验以揭示Opsins的作用 和IR检测中的TRPA1通道。我们建议识别表达Opsins的IR感应神经元 和TRPA1，并测试一个模型来解释Opsins在IR感觉中的作用。为了实现这一目标，我们设计了一个 高效监测IR吸引力和一种新的分子遗传方法绕过困难的测定法 在结合多个遗传元件的过程中。 AIM 2利用了我们在另一个TRP中创建的突变 （TRPV-A），使男性和女性聋。我们将测试蜂群中听力和TRPV-A的作用 在交配和寻找人类时形成。 AIM 2还将基于男性交配需要的观察 由TRPV-A介导的试听，以设计一种策略来克服主要障碍，限制了限制的功效 无菌昆虫技术（SIT）。 SIT是抑制AE的有前途的策略。埃及。它涉及淹没当地的 无菌雄性的人口，然后在交配时使女性无菌。使用SIT的障碍是 野生型男性胜过无菌男性。我们建议操纵TRPV-A-活性 表达听觉神经元可以提高无菌男性交配的成功，从而提高SIT的功效 在抑制AE时。埃及。 AIM 3关注确定驱虫剂的感觉受体。我们建议测试 Opsin充当驱虫剂的高度敏感受体的想法。如果由 提出的实验，这将表明Opsins包含一类新的嗅觉受体。到 实现我们的目标，我们开发了大量的最先进方法曲目。这些 包括新的分子遗传工具，一套行为分析，原始视频跟踪软件和体内 电生理记录。总而言之，该项目将揭示Opsins和TRP频道的作用 允许蚊子感知人类和同种伴侣。这项工作收集的见解 令人兴奋的潜力，可以制定控制AE的创新策略。埃及并减少昆虫传播疾病。