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Peptide regulation of blood-feeding and mating physiology in mosquitoes

蚊子吸血和交配生理的肽调节

基本信息

批准号：
10626130
负责人：
Laura Duvall
金额：
$ 40.24万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10626130
关键词：
Affect Anatomy Animals Behavior Behavioral Biology Bite Blood Cells Culicidae Dengue Fever Development Disease Disease Vectors Doctor of Philosophy Ensure Environmental Risk Factor Fathers Feeding behaviors Female Genetic Techniques Human Human Bites Individual Instinct Label Ligands Liquid substance Malaria Maps Mediating Mosquito Control Neuropeptides Nutritional Partner in relationship Pathway interactions Peptide Signal Sequences Peptides Perception Phase Physiological Physiology Play Proteins Public Health Regulation Reproduction Research Project Grants Resources Satiation Sensory Signal Pathway Signal Transduction Techniques Work ZIKA chikungunya detection of nutrient drug action egg feeding innovation male mating behavior motivated behavior offspring pathogen pharmacologic prevent receptor response screening small molecule transmission process vector vector control weapons

项目摘要

Project Summary PD/PI: Laura B. Duvall PhD Mosquitoes are obligate blood-feeders that pose increasing threats to global public health by spreading diseases, including Zika and malaria, among humans. Innate behaviors, including blood-feeding and mating, play key roles in vector biology and undergo dramatic changes influenced by environmental factors and internal state but we know little about the physiological changes underlying the behavioral readout. Our work focuses on understanding how neuropeptides regulate organismal physiology in mosquitoes. Specifically, how these peptides influence blood-feeding and utilization and post-mating responses. After a full meal of blood, female mosquitoes suppress their drive to bite humans for several days until they have matured and laid eggs. Behavioral suppression consists of several phases that are influenced by fluid regulation, nutrient sensing and satiety, and egg development. Although it is clear that these pathways influence each other, exactly how these individual components combine to produce the full expression of behavioral suppression remains unknown. We will use a combination of pharmacological and genetic techniques to ask how these pathways interact with each other on a signaling level as well as an anatomical level. Female mating responses are strongly regulated by peptide signals transferred from males to females. These signals prevent the female from accepting subsequent mates, ensuring the first male fathers all of her offspring, and allow her to allocate nutritional resources for reproduction. Using high-throughput cell-based screening techniques to pair ligands with receptors we will identify key receptors in the female that mediate post-mating responses and find small molecule drugs that act on them. We will map the anatomy that underlies post-mating responses using cutting-edge genetic techniques that enable us to label and manipulate the cells that express these receptors. These findings will increase our mechanistic understanding of how neuropeptide signaling acts on anatomical circuits to modulate chemosensory perception and motivated behavior. Additionally, these results will provide the basis for innovative approaches to mosquito control since receptors that affect mating and biting could be “weaponized” against mosquitoes to disrupt these behaviors. Directly targeting behaviors that contribute to the spread of diseases offers an effective vector control solution by preventing transmission of all of the pathogens carried by these animals.

项目摘要PD/PI：Laura B.Duvall博士蚊子是义务的血液喂食者，通过以下方式对全球公共健康构成越来越大的威胁在人类之间传播疾病，包括寨卡病毒和疟疾。先天行为，包括觅血和交配，在媒介生物学中扮演着关键角色，并经历了戏剧性的变化受环境因素和内部状态的影响，但我们对生理状况知之甚少行为读数的变化。我们的工作重点是了解神经肽调节蚊子的生物体生理。具体地说，这些肽是如何影响血液的摄取和利用以及交配后的反应。在饱餐了一顿血之后，雌性蚊子抑制了几次咬人的冲动几天后它们就会成熟并产卵。行为抑制由几个阶段组成受体液调节、营养感知和饱腹感以及卵子发育的影响。尽管很明显，这些途径相互影响，但这些个体到底是如何组件组合以产生行为抑制的完整表达残留物未知。我们将使用药理学和遗传学技术的组合来询问这些通路在信号水平和解剖水平上相互作用。雌性交配反应强烈地受到从雄性传递到女性。这些信号阻止雌性接受后续的交配，从而确保第一次交配雄性为她所有的后代做父亲，并允许她为繁殖分配营养资源。使用高通量细胞筛选技术将配体与受体配对，我们将确定雌性体内调节交配后反应的关键受体，并找到小分子对他们起作用的药物。我们将绘制交配后反应的基础解剖图，使用尖端的基因技术，使我们能够标记和操纵表达这些受体。这些发现将增加我们对神经肽信号如何作用的机制的理解关于调节化学感觉和动机行为的解剖回路。此外，这些结果将为创新的蚊子控制方法提供基础。因为影响交配和叮咬的受体可以被用来对抗蚊子扰乱这些行为。直接针对导致疾病传播的行为提供有效的媒介控制解决方案，防止所有病原体的传播由这些动物携带。