Molecular Basis of Juvenile Hormone Action in Insect Development

保幼激素(JH)是昆虫内分泌系统的重要组成部分。JH参与调节一系列异常广泛的生理和发育过程。除了控制昆虫蜕皮和建立生殖成熟度外，它还控制迁徙和性行为、生殖滞育、种级决定等。本建议的重点是JH作用的分子遗传学机制。在他之前的工作中，PI描述了一组基因，这些基因的表达是由JH在果蝇中诱导的。其中一个基因编码核激素受体E75A。基于E75是一个主要的JH靶标，并且其JH诱导性在进化分化的昆虫中是保守的，PI建议寻找参与E75基因转录的激素激活的调节元件。生物信息学方法将在培养细胞中进行功能分析。第二个目标是测试核激素受体分子在JH信号中的作用。果蝇基因组编码21个核受体超家族成员。为了确定它们参与JH信号转导，PI将使用RNAi，这是一种由dsRNA触发的功能基因沉默。抑制核受体可能对JH激活培养细胞的基因表达产生抵抗。这项拟议的研究结合了细胞和计算生物学方法来定义参与基因组JH作用的分子元件，从而为难以捉摸的JH受体铺平了道路。学生将通过达特茅斯学院现有的学术支持计划参与科学研究。

Juvenile hormone (JH) is a major component of the insect endocrine system. JH is involved in regulation of an unusually extensive range of physiological and developmental processes. In addition to the control of insect molting and the establishment of reproductive maturity, it controls migratory and sexual behavior, reproductive diapause, caste determination, etc. The focus of this proposal is on the molecular genetic mechanism of JH action. In his previous work, the PI has described a group of genes, whose expression is induced by JH in Drosophila. One of the genes encodes the nuclear hormone receptor, E75A. Based on the observation that E75 is a primary JH target and its JH inducibility is conserved in evolutionarily divergent insects, the PI proposes a search for regulatory elements involved in the hormonal activation of E75 gene transcription. The bioinformatics approach will be followed up with functional assays in cultured cells. The second objective is to test the involvement of nuclear hormone receptor molecules in JH signaling. The Drosophila genome encodes 21 nuclear receptor superfamily members. To identify their involvement in JH signaling, the PI will employ RNAi, a functional gene silencing triggered by dsRNA. Suppression of nuclear receptors may confer a resistance to the JH activation of gene expression in cultured cells. The proposed research combines cellular and computational biology approaches to define molecular elements that are involved in genomic JH action and thus paves the way to an elusive JH receptor. Students will be involved in the scientific research through academic support programs that exist at Dartmouth College.