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.

项目摘要 蚊子传播了许多人类病原体，例如登革热病毒和恶性疟原虫， 每年至少造成至少一百万人死亡。除了绝缘耐药性上升和 其他因素，越来越多的证据表明，当前控制蚊子种群的策略正在 由蚊子高水平的行为和物理可塑性所赋予的弹性混淆。在 特别是，生物节奏对于疾病的传播至关重要，因为它们使蚊子能够活跃，并且 在可用主机时，有时会响应主机提示。但是，目的地清晰流行病学 相关性，我们对计时生物学与时相互作用的机制知之甚少 蚊子的嗅觉行为。为了解决这个关键知识差距，我们已经建立了一个综合性和 多学科方法将为阐明神经和分子提供创新的关键步骤 感官处理规则，指导蚊子的嗅觉节奏。我们在这里建议将此策略用于 分析每日节奏，嗅觉检测和 加工和嗅觉介导的行为中的埃及蚊子中的行为。 我们将首先确定嗅觉灵敏度和嗅觉编码的节奏如何 触角叶在对宿主相关挥发物的行为反应中有助于节奏。在第二个目标中，我们 将进一步分析昼夜节律如何调节蚊子的大脑和触角转录组，以及 通过使用CRISPR/CAS9来敲除时钟基因表达，从而产生心律失常的第一线。 最后，我们将结合行为方法和转录组分析（单细胞RNA测序），以识别 负责蚊子行为与宿主可用性同步的细胞类型。第三个目标 进一步提供了蚊子大脑活动的节奏调节的大规模表征，并定义 细胞调节状态的节奏。 完成后，这些目标将阐明嗅觉的神经和分子过程 行为每天在AE中有所不同。埃及蚊子。不仅预期拟议的工作将提供新的机械 深入了解蚊子的生物节奏，并产生第一个时钟敲除蚊子线，但也 揭示了破坏蚊子互动并告知新目标和方法的强大潜力 可以抵消蚊子行为可塑性的综合矢量管理策略。