Peptide regulation of blood-feeding and mating physiology in mosquitoes

项目总结PD/PI：Laura B。杜瓦尔博士 蚊子是专性吸血动物，对全球公共卫生构成越来越大的威胁， 传播疾病，包括寨卡病毒和疟疾。先天行为，包括 吸血和交配在病媒生物学中起着关键作用， 受环境因素和内部状态的影响，但我们对生理 行为读数的潜在变化。我们的工作重点是了解 神经肽调节蚊子的生理机能。具体来说，这些肽 影响吸血和利用以及交配后的反应。 在饱餐一顿血之后，雌性蚊子会抑制它们叮咬人类的冲动， 直到它们成熟并产卵。行为抑制包括几个阶段 它们受体液调节、营养感和饱腹感以及卵子发育的影响。 虽然很明显，这些途径相互影响，但这些个体究竟是如何相互影响的？ 成分联合收割机产生的行为抑制的充分表达仍然存在 未知我们将使用药理学和遗传学技术相结合的方法来研究 这些途径在信号传导水平以及解剖学水平上相互作用。 雌性交配反应受雄性传递到雌性的肽信号的强烈调节。 女性这些信号阻止雌性接受随后的配偶，确保了第一次交配。 男性父亲拥有她所有的后代，并允许她分配生殖的营养资源。 使用高通量的基于细胞的筛选技术将配体与受体配对，我们将 确定雌性中介导交配后反应的关键受体，并找到小分子 药物对它们起作用。我们将绘制交配后反应的解剖结构， 尖端的遗传技术，使我们能够标记和操纵细胞， 这些受体。 这些发现将增加我们对神经肽信号作用机制的理解 调节化学感觉知觉和动机行为。 此外，这些结果将为蚊子控制的创新方法提供基础 因为影响交配和叮咬的受体可以被“武器化”来对付蚊子， 破坏这些行为。直接针对助长疾病传播的行为 通过防止所有病原体的传播， 由这些动物携带。

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.