New Targets for Reproductive Control of Mosquito Vectors

蚊媒控制繁殖的新目标 项目摘要/摘要 在这个项目中，我们将研究一种主要的雄性精液蛋白。 登革热、寨卡和基孔肯雅病毒的病媒：黄热病蚊子 (埃及伊蚊)。昆虫SFP引发女性生理的重大变化，有利于 高繁殖力(例如增加产卵量)，调节再交配，在蚊子中， 潜在地调节血液喂养生理学。登革热是一种古老的祸害，但却是新的 基孔肯雅热和寨卡病毒等病原体在它们的森林背景下静静地循环 冲上前去，以复仇的方式横跨半球。有一个 迫切需要为这些设备开发新的和有效的矢量控制策略 向量。在目前的资助期间，我们发现了伊蚊SFP，并获得了生物活性 馏分和已鉴定的成分。我们开发了一种测试方法来测试 组件，并已成功地使用基于CRISPR的基因组编辑来 突变我们的第一批生物活性SFP候选者。我们还确定了交配的影响 在雄性的SFP存储(和生产)上，在交配的雌性的转录组上。 在这次续签申请中，为了继续支持这个项目，我们提出了三项建议 目的：(1)鉴定Ae体内具有生物活性的SFP，并对其功能进行鉴定。 埃及伊蚊，(2)确定雌性分子对SFP的一般和生理反应 和对特定的、生物活性的SFP的分子反应，以及(3)了解表型 田间相关群体中SFP及其反应靶标的遗传变异 这种蚊子媒介的。我们的目标是确定SFP和SFP目标，即 作为一种新的生殖控制手段来操纵，或用来改变血液供应 这些传播致命病原体的昆虫的生理学，长期目标是 减少或消除病毒对人的传播。

New Targets for Reproductive Control of Mosquito Vectors Project summary/abstract In this project, we will investigate the male seminal fluid proteins (SFPs) of a major disease vector of dengue, Zika and chikungunya viruses: the yellow fever mosquito (Aedes aegypti). Insect SFPs trigger major changes in female physiology, conducive to high fertility (e.g. increased egg production), regulating re-mating and, in mosquitoes, potentially regulating blood feeding physiology. Dengue is an old scourge, but new pathogens such as chikungunya and Zika that cycled silently in their sylvatic backdrop have surged forward and crossed hemispheres with a vengeance. There is an immediate need to develop novel and effective vector control strategies for these vectors. In the present funding period, we identified Aedes SFPs and obtained bioactive fractions and identified components. We developed assays for testing the effects of the components, and have been successful in using CRISPR-based genome editing to mutate our first candidates for bioactive SFPs. We also determined the effect of mating on SFP stores (and production) in males, and on the transcriptome of the mated female. In this renewal application, for continued support for this project, we propose three specific aims to (1) identify and functionally characterize bioactive SFPs in vivo in Ae. aegypti, (2) determine female molecular responses to SFPs in general and physiological and molecular responses to specific, bioactive, SFPs and (3) understand the phenotypic and genetic variation of SFPs and their responsive targets in field relevant populations of this mosquito vector. Our goal is to identify SFPs, and SFP targets, that could be manipulated as a novel means of reproductive control, or to modify the blood feeding physiology of these insects that transmit deadly pathogens, with the long-term goal to reduce or eliminate virus transmission to people.