Regulation of juvenile hormone titers in mosquitoes

描述（由申请人提供）：蚊媒寄生虫病是世界上主要的死亡和发病原因之一。最近，疟疾和登革热等蚊媒疾病的发病率急剧增加，蚊子对杀虫剂的广泛耐药性突出表明，需要采用基于蚊子特异性药剂的昆虫控制新方法。这种蚊子特异性控制剂的发现取决于对蚊子生物学的基础研究。幼体激素（JH）是昆虫体内主要的激素调节因子。在雌蚊中，JH标志着完成了向成虫阶段的蜕化，并开始了生殖过程。JH滴度主要由配体（CA）合成JH的速率决定。我们的研究采用有机、细胞和分子水平实验相结合的综合方法，揭示了蚊子对JH活性的调节具有独特的特征，这些特征与适应供血和卵巢发育的周期调节有关。我们已经描述了雌蚊的CA在高和低生物合成活性之间交替，这与发育程序和营养信号有关。我们已经确定了刺激或抑制JH合成的神经肽，并表征了它们的受体。我们首次对昆虫内分泌腺进行了基因组分析，并研究了大多数JH生物合成酶的表达。我们还描述了幼虫阶段积累的营养物质调节CA活性，并开发了一种独特的营养缺乏蚊子模型，这些蚊子不能合成JH。本项目的目的是了解控制CA活性的不同因子（allatregulatory factors）的作用和作用机制。我们还试图确定JH合成的限速步骤和调控点。为了实现这些目标，我们将重点关注两个关键阶段：1)新出现的成年雌性JH合成的激活和2)血液喂养后CA的失活。这两个阶段是蚊子生殖成熟的关键时刻，也为疾病控制提供了良好的实验模型。这些研究领域应该确定目标，以便设计适合发展中国家控制蚊子的新的、具体的和负担得起的化学战略。

DESCRIPTION (provided by applicant): Mosquito-transmitted parasitic diseases are among the major causes of mortality and morbidity in the world. Recent dramatic increases in the incidence of mosquito-borne diseases, like malaria and dengue fever, and the wide-spread resistance of mosquitoes to insecticides underscores the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on basic research on the biology of mosquitoes. Juvenile hormone (JH) is a major hormonal regulator in insects. In the female mosquito, JH signals the completion of the ecdysis to the adult stage, and initiates reproductive processes. JH titer is essentially determined by the rate at which the corpora allata (CA) synthesizes JH. Our research, using an integrative approach that combines experiments at the organismal, cellular and molecular level, is revealing that mosquito regulation of JH activity has unique features that are related to the adaptation to blood-feeding and the cyclic regulation of ovarian development. We have described that the CA of the female mosquito alternates between periods of high and low biosynthetic activity that are linked to developmental programs and nutritional signals. We have identified neuropeptides that stimulate or inhibit JH synthesis and have characterized their receptors. We have performed the first genomic analysis of an insect endocrine gland and studied the expression of most of the JH biosynthetic enzymes. We have also described that nutrients accumulated during the larval stages regulate CA activity and developed a unique model of nutritionally deficient mosquitoes that do not synthesize JH. The goal of this project is to understand the role and mechanism of action of the different factors that control CA activity (allatoregulatory factors). We also seek to identify the rate limiting steps and regulatory points of JH synthesis. To accomplish these goals, we will focus on two key stages: 1) the activation of JH synthesis in the newly emerged adult female and 2) the inactivation of the CA after blood- feeding. These two stages are critical moments in the reproductive maturation of mosquitoes and make excellent experimental models that are also relevant for disease control. These areas of research should identify targets for designing new, specific and affordable chemical strategies suitable for mosquito control in developing countries.