Molecular Basis of Juvenile Hormone Action in Insect Development

昆虫发育中保幼激素作用的分子基础

• 批准号: 0653567
• 负责人: Edward Dubrovsky
• 金额: $ 37.79万
• 依托单位: Fordham University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0653567&HistoricalAwards=false
• 关键词: Molecular; Basis; Juvenile; Hormone; Action

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.

保幼激素是昆虫内分泌系统的主要成分。JH参与调节异常广泛的生理和发育过程。除了控制昆虫蜕皮和生殖成熟的建立外，它还控制迁飞和性行为、生殖滞育、种姓决定等，本提案的重点是JH作用的分子遗传机制。在他以前的工作中，PI描述了一组基因，其表达被JH诱导。其中一个基因编码核激素受体E75A。基于E75是JH的主要靶点，并且其JH诱导因子在进化趋异的昆虫中是保守的这一观察结果，PI提出了对参与E75基因转录的激素激活的调控元件的搜索。生物信息学方法将在培养细胞中进行功能测定。第二个目标是测试核激素受体分子参与JH信号传导。果蝇基因组编码21个核受体超家族成员。为了鉴定它们参与JH信号传导，PI将采用RNAi，一种由dsRNA触发的功能性基因沉默。核受体的抑制可赋予对培养细胞中基因表达的JH活化的抗性。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项目参与科学研究。