Regulation of juvenile hormone titers in mosquitoes

描述（由申请人提供）：蚊子传播的寄生虫病是世界上死亡和发病的主要原因。最近蚊子传播的疾病，如疟疾和登革热的发病率急剧增加，以及蚊子对杀虫剂的广泛耐药性，强调了对基于蚊子特异性试剂的昆虫控制新方法的需求。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。保幼激素（JH）是昆虫体内主要的激素调节剂。在雌性蚊子中，JH发出完成蜕皮到成虫阶段的信号，并启动生殖过程。JH滴度基本上由咽侧体（CA）合成JH的速率决定。我们的研究采用了一种综合方法，结合了生物体，细胞和分子水平的实验，揭示了蚊子对JH活性的调节具有独特的特征，这些特征与对吸血的适应和卵巢发育的周期性调节有关。我们已经描述了雌蚊的CA在与发育程序和营养信号相关的高和低生物合成活性时期之间交替。我们已经确定了刺激或抑制JH合成的神经肽，并确定了其受体的特征。我们已经进行了第一个昆虫内分泌腺的基因组分析，并研究了大多数JH生物合成酶的表达。我们还描述了在幼虫阶段积累的营养物质调节CA活性，并开发了一个独特的模型，营养缺乏的蚊子不合成JH。本项目的目标是了解控制CA活动的不同因素（allatoregulatory factors）的作用和作用机制。我们还试图确定速率限制步骤和JH合成的调节点。为了实现这些目标，我们将集中在两个关键阶段：1）在新出现的成年雌性中JH合成的激活和2）吸血后CA的失活。这两个阶段是蚊子生殖成熟的关键时刻，也是与疾病控制相关的优秀实验模型。这些研究领域应确定目标，以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.