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: 10493295
• 负责人: CRAIG MONTELL
• 金额: $ 55.5万
• 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/10493295
• 关键词: Address; Aedes; Agriculture; Animals; Auditory; Behavior; 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; Female sterility; G-Protein-Coupled Receptors; Genetic; Glean; Goals; Hearing; Homing; Human; Infrared Rays; Insect Repellents; Insecta; Lead; Light; Male Sterility; Mediating; Modeling; Molecular Genetics; Monitor; 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; Stimulus; 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; human female; improved; in vivo; innovation; insight; male; member; multimodality; olfactory receptor; prevent; receptor; sensor; sex; sterile insect technique; success; tool

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.

摘要 埃及伊蚊传播登革热、寨卡病毒、黄热病等疾病，以及其他困扰&GT；100的疾病 每年有几百万人。这些蚊子依靠多个敏锐的感官来定位人类的血液宿主 食物，以及寻找交配的相似之处。目前，我们对此只有一个初步的了解。 控制这些关键行为的受体。拟议研究的目标就是解决这一差距。这个 这项提案的统一主题是检验OPSIN和TRP通道是两个关键类别的想法 在感觉和控制Ae的行为中具有广泛作用的信号蛋白。埃及伊蚊。视紫红质是 创始的G蛋白偶联受体(GPCRs)。我们最近发现，OPTINS是多模式的 感官感受器，挑战100年来它们只探测光的教条。去寻找人类，雌性Ae。 埃及人整合了来自不同刺激的信息，包括二氧化碳、视觉线索、有机分子和 皮肤的对流热。我们发现了另一条线索。AIM 1建立在我们的初步数据基础上。埃及伊蚊 使用红外线(IR)辐射作为额外的宿主刺激。我们概述了实验以揭示视蛋白的作用。 和红外检测中的TRPA1通道。我们建议鉴定表达视蛋白的红外线感觉神经元 和TRPA1，并测试一个模型来解释视蛋白在IR感觉中的作用。为了实现这一目标，我们设计了一种 监测IR吸引的高效方法和绕过困难的新分子遗传学方法 在结合多种遗传元素方面。Aim 2利用了我们在另一个TRP中创建的突变 (TRPV-A)，使男性和女性耳聋。我们将测试听力和TRPV-A在群体中的作用 在交配和寻找人类的过程中。目标2也将建立在雄性交配需要观察的基础上 由TRPV-A介导的试听，以制定一项战略，以克服限制疗效的主要障碍 昆虫不育技术(SIT)。SIT是一种很有前途的抑制Ae的策略。埃及伊蚊。它涉及淹没一个当地人 雄性不育的种群，然后在交配时使雌性不育。使用SIT的一个障碍是 野生型雄性在竞争中胜过不育雄性。我们建议，对TRPV-A活性的操纵- 表达听神经元可以提高雄性不育交配成功率，从而提高SITE的效率 在压制Ae.埃及伊蚊。目标3涉及识别驱避剂的感官受体。我们打算测试一下 视蛋白是驱虫剂高度敏感的感受器的观点。如果得到 拟议的实验，这将证明视蛋白组成了一种新的嗅觉受体。至 为了实现我们的目标，我们开发了一系列最先进的方法。这些 包括新分子遗传工具、一套行为分析、原创视频跟踪软件和体内 电生理记录。综上所述，本项目将揭示Opsins和Trp通道在 使蚊子能够感知人类和同种配偶。从这项工作中收集到的见解有 令人兴奋的潜力，导致创新的战略，以控制埃博拉。埃及伊蚊和减少昆虫传播的疾病。