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，因为蚊子需要血液来产卵。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它们自己的生命周期。因此，了解在这些载体中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。因此，我们将破译调节雌性蚊子繁殖的激素遗传途径；通过转录组学、生物信息学和RNA干扰分析，研究控制埃及伊蚊雌性脂肪体（FB，卵子发育所必需的组织）羽化后发育的幼年激素调节级联。我们还将破译20-羟基蜕皮激素调节级联在控制埃及伊蚊卵黄形成进展关键基因中的差异作用。我们将确定负责共同调节FB基因表达特定模式的顺式基序。新开发的蚊子GAL4-UAS基因系统将允许测试这些启动子。这种遗传系统在评估基因的功能方面也是无价的，在转录组筛选中，通过它们的错误调节或rnai耗竭来鉴定基因。这一综合性研究项目的完成将极大地促进我们对蚊子繁殖的分子基础的理解，所得到的数据将为破译蚊子控制的新靶点奠定基础。

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.