Molecular Basis of Ecdysteroid Action in the Mosquito

描述（由申请人提供）：许多毁灭性的人类疾病是由蚊子传播的，因为它们需要吸血来进行卵的发育。致病病原体已经成功地适应了利用蚊子生物学的这一特征来实现自己的生命周期。因此，了解这些载体中控制卵发育的分子机制对于设计破坏疾病传播的新方法至关重要。因此，我们将破译激素的遗传途径，调节蚊子雌性生殖;保幼激素调节级联管理的埃及伊蚊雌性脂肪体（FB的羽化后的发展，卵发育必不可少的组织）将通过转录组，生物信息学和RNA干扰分析进行调查。我们还将破译20-羟基蜕皮激素调节级联反应在控制基因的差异行动的关键进展，卵黄在A。埃及人。我们将确定负责共同调节FB基因表达的特定模式的顺式基序。新开发的蚊子GAL 4-UAS遗传系统将允许测试这些启动子。该遗传系统在评估转录组筛选中通过其错误调节或RNAi耗尽鉴定的基因功能方面也是非常宝贵的。这一综合研究计划目标的实现将大大推进我们对蚊子繁殖的分子基础的理解，由此产生的数据将为破译蚊子控制的新目标奠定基础。 公共卫生相关性：蚊子传播许多毁灭性的人类疾病，因为它们需要血饲料来发育卵。致病病原体已经成功地利用了蚊子生物学的这一特点。因此，了解控制卵子发育的分子机制对于设计新的方法来破坏疾病传播至关重要。在这个研究项目中，我们将阐明调节蚊子雌性生殖的激素遗传途径，这方面的知识将为破译蚊子控制的新目标奠定基础。

DESCRIPTION (provided by applicant): Many devastating human diseases are transmitted by mosquitoes because of their requirement to blood feed for egg development. Disease-causing pathogens have adapted successfully to exploit this feature of mosquito biology for their own life cycles. Hence, the understanding of molecular mechanisms controlling egg development in these vectors is essential for devising novel methods to disrupt disease spread. We will thus decipher the hormonal genetic pathways that regulate mosquito female reproduction; the juvenile hormone regulatory cascade governing the post-eclosion development of the Aedes aegypti female fat body (FB; the tissue essential for egg development) will be investigated by means of transcriptome, bioinformatics, and RNA interference analyses. We will also decipher the differential action of the 20-hydroxyecdysone regulatory cascade in controlling genes critical for the progression of vitellogenesis in A. aegypti. We will determine cis motifs responsible for co-regulating specific patterns of FB gene expression. The newly developed mosquito GAL4-UAS genetic system will permit testing these promoters. This genetic system is also invaluable in evaluating functions of genes, identified in transcriptomic screens, by means of their mis-regulation or RNAi-depletion. Accomplishment of the goals of this comprehensive research program will significantly advance our understanding of the molecular basis of mosquito reproduction, and the resulting data will build a foundation for deciphering new targets for mosquito control. PUBLIC HEALTH RELEVANCE: Mosquitoes transmit many devastating human diseases because of their requirement to blood feed for egg development. Disease-causing pathogens have successfully adapted to exploit this feature of mosquito biology. The understanding of molecular mechanisms controlling egg development is thus essential for devising novel methods to disrupt disease spread. In this research project, we will elucidate hormonal genetic pathways regulating mosquito female reproduction, the knowledge of which will build a foundation for deciphering new targets for mosquito control.