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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的埃及伊蚊传播登革热、寨卡、黄热病等疾病，以及其他影响超过 100 人的疾病每年 100 万人。这些蚊子依靠多种敏锐的感官来定位人类宿主并获取血液食物，以及寻找交配的同种动物。目前，我们对它还只有初步的了解控制这些关键行为的受体。拟议研究的目标是解决这一差距。这该提案的统一主题是测试视蛋白和 TRP 通道是两个关键类别的想法在伊蚊的感觉和控制行为中发挥广泛作用的信号蛋白。埃及伊蚊。视紫质是最初的 G 蛋白偶联受体 (GPCR)。我们最近发现视蛋白是多模式的感觉受体，挑战了 100 年来它们只能感知光的教条。寻找人类，女Ae。埃及伊蚊整合来自不同刺激的信息，包括二氧化碳、视觉线索、有机分子和来自皮肤的对流热量。我们发现了另一个线索。目标 1 建立在我们 Ae 的初步数据之上。埃及伊蚊使用红外（IR）辐射作为额外的宿主刺激。我们概述了揭示视蛋白作用的实验以及红外检测中的 TRPA1 通道。我们建议识别表达视蛋白的红外传感神经元和 TRPA1，并测试一个模型来解释视蛋白在红外感觉中的作用。为了实现这一目标，我们设计了一个用于监测红外吸引力的高效测定法和绕过困难的新分子遗传学方法结合多种遗传元素。目标 2 利用了我们在另一个 TRP 中创建的突变（TRPV-A），使男性和女性失聪。我们将测试听觉和 TRPV-A 在群体中的作用形成、交配和寻找人类。目标 2 还将建立在雄性交配所需的观察基础上由 TRPV-A 介导的试镜，旨在制定一种策略来克服限制效果的主要障碍昆虫不育技术（SIT）。 SIT 是一种很有前景的抑制伊蚊的策略。埃及伊蚊。它涉及淹没当地具有不育雄性的种群，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。我们建议操纵 TRPV-A- 的活性表达听觉神经元可提高不育雄性交配成功率，从而提高 SIT 的功效抑制Ae。埃及伊蚊。目标 3 涉及识别驱虫剂的感觉受体。我们建议测试视蛋白作为驱虫剂的高度敏感受体的想法。如果经确认拟议的实验，这将证明视蛋白包含一类新的嗅觉受体。到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。总之，该项目将揭示视蛋白和 TRP 通道在让蚊子能够感知人类和同种伴侣。从这项工作中收集到的见解令人兴奋的潜力导致控制AE的创新策略。埃及伊蚊并减少虫媒疾病。