Neural and molecular rules of mosquito olfactory rhythms

蚊子嗅觉节律的神经和分子规则

• 批准号: 10298722
• 负责人: Clement Vinauger
• 金额: $ 56.18万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10298722
• 关键词: Address; Aedes; Affect; Afferent Neurons; Beds; Behavior; Behavioral; Behavioral Assay; Biological Rhythm; Blood; Brain; CRISPR/Cas technology; Cells; Cessation of life; Characteristics; Chronobiology; Clustered Regularly Interspaced Short Palindromic Repeats; Cues; Culicidae; Data; Dengue Virus; Detection; Dissection; Electrophysiology (science); Epidemiology; Flying body movement; Gene Expression; Genes; Genetic; Goals; Head; Insecticide Resistance; Insecticides; Knock-out; Knowledge; Light; Lobe; Mediating; Methods; Molecular; Monitor; Mosquito Control; Nature; Neurons; Odorant Receptors; Odors; Orthologous Gene; Pacemakers; Pattern; Perception; Periodicity; Peripheral; Physiological; Plasmodium falciparum; Population; Probability; Process; Regulation; Research; Sensory; Smell Perception; Testing; Time; Translating; Ursidae Family; Variant; Work; base; behavioral plasticity; behavioral response; cell type; circadian; circadian pacemaker; disease transmission; experimental study; human pathogen; improved; innovation; insight; interdisciplinary approach; molecular clock; mutant; odorant-binding protein; relating to nervous system; resilience; response; single-cell RNA sequencing; transcriptome; transcriptome sequencing; transcriptomics; vector management strategies

PROJECT SUMMARY Mosquitoes transmit numerous human pathogens, such as dengue virus and Plasmodium falciparum, collectively responsible for at least one million deaths each year. In addition to rising insecticide resistance and other factors, it has become increasingly evident that current strategies to control mosquito populations are being confounded by the resilience conferred by mosquitoes’ high levels of behavioral and physiological plasticity. In particular, biological rhythms are crucial to disease transmission as they allow mosquitoes to be active and responsive to host cues at times of the day when hosts are available. However, despite clear epidemiological relevance, we know very little about the mechanisms underlying the interaction between the chronobiology and the olfactory behavior of mosquitoes. To address this key knowledge gap, we have developed an integrative and multidisciplinary approach that will provide innovative critical steps towards elucidating the neural and molecular rules of sensory processing that guide mosquitoes’ olfactory rhythms. We propose here to use this strategy for analyzing the mechanistic underpinnings of the interaction between daily rhythms, olfactory detection and processing, and olfactory-mediated behaviors in Aedes aegypti mosquitoes. We will first determine how rhythms in olfactory sensitivity and in olfactory encoding at the level of the antennal lobe contribute to rhythms in the behavioral responses to host-related volatiles. In a second aim, we will further analyze how circadian clocks modulate the brain and antennal transcriptome of mosquitoes, and generate the first line of arrhythmic mosquitoes, by using CRISPR/Cas9 to knockout clock gene expression. Finally, we will combine behavioral methods and transcriptomic analysis (single-cell RNA sequencing) to identify the cell-types responsible for the synchronization of mosquito behavior with host-availability. This third aim will further provide a large-scale characterization of the rhythmic regulation of mosquito brain activity, and define rhythms in cell regulatory states. Upon completion, these aims will shed light on the neural and molecular processes by which olfactory behaviors vary daily in Ae. aegypti mosquitoes. Not only the proposed work is expected to offer new mechanistic insights into the biological rhythms of mosquitoes and generate a first clock knockout mosquito line, but it also bears strong potential for revealing new targets and methods for disrupting mosquito-host interactions and inform an integrated vector management strategy that can counteract mosquito behavioral plasticity.

项目概要 蚊子传播多种人类病原体，例如登革热病毒和恶性疟原虫， 除了杀虫剂耐药性不断上升之外，每年还造成至少一百万人死亡。 考虑到其他因素，越来越明显的是，目前控制蚊子数量的策略正在被改变。 蚊子的高水平行为和生理可塑性所赋予的恢复力令人困惑。 特别是，生物节律对于疾病传播至关重要，因为它们使蚊子变得活跃和活跃。 然而，尽管有明确的流行病学证据，但在一天中当宿主有空的时候，它们会对宿主的提示做出反应。 相关性，我们对时间生物学和时间生物学之间相互作用的机制知之甚少。 为了解决这一关键的知识差距，我们开发了一种综合性的和蚊子的嗅觉行为。 多学科方法将为阐明神经和分子机制提供创新的关键步骤 我们在这里建议使用这种策略来实现蚊子引导嗅觉节律的感觉处理规则。 分析日常节律、嗅觉检测和嗅觉检测之间相互作用的机制基础 埃及伊蚊的加工和嗅觉介导的行为。 我们将首先确定嗅觉敏感性和嗅觉编码水平的节律如何 触角叶有助于对宿主相关挥发物的行为反应的节律。 将进一步分析生物钟如何调节蚊子的大脑和触角转录组，以及 通过使用 CRISPR/Cas9 敲除时钟基因表达，产生第一批无节律蚊子。 最后，我们将结合行为方法和转录组分析（单细胞RNA测序）来识别 第三个目标是负责蚊子行为与宿主可用性同步的细胞类型。 进一步提供了蚊子大脑活动节律调节的大规模表征，并定义 细胞调节状态的节律。 完成后，这些目标将揭示嗅觉的神经和分子过程 埃及伊蚊的行为每天都在变化，这项工作不仅有望提供新的机制。 深入了解蚊子的生物节律并产生第一个时钟敲除蚊子系，但它也 具有揭示破坏蚊子与宿主相互作用的新目标和方法的巨大潜力，并提供信息 一种可以抵消蚊子行为可塑性的综合病媒管理策略。