Olfactory receptors and neurons regulating odor-guided behaviors in mosquitoes

调节蚊子气味引导行为的嗅觉受体和神经元

基本信息

批准号：
10455031
负责人：
Christopher John Potter
金额：
$ 52.02万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-17 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10455031
关键词：
Address Adoption Aedes Affect Agriculture Anatomy Anopheles Genus Anopheles gambiae Arthropod Vectors Behavior Behavioral Assay Biological Assay Biology Bite Calcium Cessation of life Chemicals Chironomus thummi Cues Culex (Genus)Culicidae Data Developed Countries Development Disease Disease Vectors Electrophysiology (science)Eugenol Exhibits Fleas Genetic Genetic Techniques Hair Human Human body Image Insect Repellents Insect Vectors Insecta Lead Link Malaria Masks Maxilla Measures Methodology Methods Mites Molecular Target Neurobiology Neurons Odorant Receptors Odors Olfactory Pathways Olfactory Receptor Neurons Pain Parasites Pattern Persons Plasmodium Production Reagent Research Sensory Signal Transduction Smell Perception System Testing Ticks Time Vector-transmitted infectious disease Work base cost genetic approach improved insight neural circuit neurogenetics novel olfactory sensory neurons prevent rational design response side effect skin irritation transcriptome sequencing vector control

项目摘要

Project Abstract/Summary Anopheles gambiae mosquitoes, as the insect vector for the Plasmodium parasite that causes malaria, were responsible for the deaths of >450,000 people last year. Fortunately, mosquitoes have a weakness that our research aims to exploit. Mosquitoes use their sense of smell for most human host-seeking behaviors. This suggests that targeting a mosquito's sense of smell could lead to effective measures that prevent bites and the spread of diseases. Indeed, spatial repellents are volatile odorants that effectively disrupt host-seeking behaviors and keep mosquitoes from approaching. They have widespread use in developed nations as personal protective measures, but global adoption is limited due to high costs, unwanted side-effects (such as skin irritation), or the need to use high-concentrations to remain effective. A major limitation to the identification of new, more tractable, repellents is a lack of understanding of how spatial repellents promote repulsion by impacting the mosquito's sense of smell. This is primarily due to challenging technical hurdles needed to link repellent and other odorants to a variety of olfactory neuron functions. Our introduction of the QF2/QUAS genetic binary system into Anopheles mosquitoes overcomes previous technical barriers, and now enables us to directly visualize the response of olfactory neurons, in living mosquitoes, to repellents and human body odors. Using a combination of calcium imaging, single sensillum electrophysiological recordings, and RNA-seq along with our established and novel genetic techniques, we will test the hypothesis that (1) spatial mosquito repellents function by masking, activating, or scrambling the activity of olfactory neurons. We will examine the activity patterns of olfactory neurons in living Anopheles gambiae mosquitoes when stimulated by 20 commonly used mosquito repellents in the presence and absence of human odorants. In addition, we will identify the odorant receptors expressed by olfactory neurons exhibiting altered activity patterns in response to each repellent. Using a combination of genetic approaches (aimed at modulating the function of targeted olfactory neurons) and behavioral assays, we will test the hypothesis that (2) spatial repellents promote repellent behaviors by altering olfactory system signaling. We will experimentally determine which olfactory neurons and what types of olfactory neuron activity changes are either necessary and/or sufficient to drive repellent behaviors. The proposed studies are significant because we will gain new mechanistic insights into how mosquito repellents target the mosquito's sense of smell and enable the development of rationale biology-based strategies to identify new repellents that are cheaper, safer, and more effective for use on a global scale to prevent the spread of disease.

项目摘要/摘要 Anopheles Gambiae蚊子，作为导致疟疾的疟原虫的昆虫载体，去年负责45万人死亡。幸运的是，蚊子有弱点我们的研究旨在利用。蚊子用他们的嗅觉用于大多数人类寻求的宿主行为。这表明针对蚊子的嗅觉可能会导致有效的措施预防叮咬和疾病的传播。实际上，空间驱蚊剂是有效的挥发性气味破坏寻求宿主的行为，并防止蚊子接近。他们广泛使用发展国家作为个人保护措施，但由于成本高昂，全球采用受到限制，不需要的副作用（例如皮肤刺激），或需要使用高浓度来保持有效的。识别新的，更可行的驱虫剂的主要限制是缺乏了解空间驱虫剂如何通过影响蚊子的嗅觉来促进击退。这主要是由于将驱虫剂和其他气味联系起来所需的挑战性技术障碍与多种嗅觉神经元功能。我们将QF2/Quas遗传二进制系统引入蚊子蚊子克服了以前的技术障碍，现在使我们能够直接可视化嗅觉神经元，生物蚊子，驱虫剂和人体气味的反应。使用钙成像，单个感觉电生理记录和RNA-Seq的组合借助我们建立的新型遗传技术，我们将检验以下假设：（1）空间蚊子驱虫剂通过掩盖，激活或扰乱嗅觉神经元的活性来发挥作用。我们将在活动脉蚊中检查嗅觉神经元的活性模式时在存在和不存在人类气味的情况下，由20种常用的蚊子刺激。此外，我们将确定嗅觉神经元表现出的气味受体改变了响应每个驱虫剂的活动模式。结合遗传方法（针对调节目标嗅觉神经元的功能）和行为分析，我们将测试假设（2）空间驱蚊剂通过改变嗅觉系统来促进驱虫行为信号。我们将通过实验确定哪些嗅觉神经元以及哪种类型的嗅觉神经元活动的变化是必要的和/或足以驱动驱动行为的。这拟议的研究很重要，因为我们将获得有关蚊子如何的新机械见解。驱虫剂以蚊子的嗅觉为目标，并能够发展基于基本生物学的基础生物学确定新的驱虫剂的策略，这些驱虫剂在全球范围内更便宜，更安全，更有效为了防止疾病的传播。