Molecular Mechanisms of Steroid Regulation in an Insect Endocrine System

昆虫内分泌系统类固醇调节的分子机制

• 批准号: 0744447
• 负责人: Randall Hewes
• 金额: $ 40.3万
• 依托单位: University of Oklahoma Norman Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0744447&HistoricalAwards=false
• 关键词: Molecular; Mechanisms; Steroid; Regulation; Insect

Peptide hormones are chemical signals that are secreted by cells to control the functioning of the brain and many other tissues. They are key regulators of diverse processes, including growth, reproduction, stress, sleep, body weight, pain, and daily rhythms. The long-term goal of this proposal is to understand the mechanisms within cells that underlie the regulation of peptide hormone signaling by steroids. Specifically, this work will define mechanisms underlying the steroid regulation of the gene encoding the peptide hormone, ecdysis-triggering hormone (ETH). Toward this end, methods were established in the fruit fly, Drosophila melanogaster, for manipulation of steroid signaling in single cells. This is combined with tracking of ETH gene expression through genetic and molecular assays, and genetic manipulations to measure the contributions to this process from steroid receptors and other interacting proteins. The cellular sites of steroid receptor action underlying the regulation of ETH gene expression, and the roles of different DNA sequences within the ETH gene, will be determined genetically and biochemically. The regulation of gene expression by steroid receptors requires the participation of co-factors. These will be identified through genetic screens. Together, these experiments will examine how co-factors for a steroid receptor can mediate cell-type specific expression of steroid hormone-responsive genes. This basic research will contribute to our understanding of the disruptions in hormone signaling associated with human diseases, such as obesity, diabetes and cancer. This work will also be a unique opportunity for several undergraduate and graduate students to participate in research. Students in Oklahoma have few options for non-agricultural training in the sciences. The experiences provided by this project are not otherwise readily available, and they complement traditional lecture-format courses. These research experiences will continue to enable and inspire talented students from the State of Oklahoma to pursue professional careers in industry, medicine, and scientific research.

肽激素是细胞分泌的化学信号，以控制大脑和许多其他组织的功能。 它们是各种过程的关键调节因子，包括生长，繁殖，压力，睡眠，体重，疼痛和每日节奏。 该提案的长期目标是了解细胞内的机制，这些机制是基于类固醇调节肽激素信号传导的基础。具体而言，这项工作将定义编码肽激素的基因的类固醇调节的机制，递归激素（ETH）。 为此，在果蝇（果蝇果蝇）中建立了方法，用于操纵单个细胞中类固醇信号。 这与通过遗传和分子测定的跟踪ETH基因表达的跟踪以及遗传操作，以测量类固醇受体和其他相互作用蛋白对此过程的贡献。 ETH基因表达调节的基础类固醇受体作用的细胞位点以及ETH基因内不同DNA序列的作用将在遗传和生化上确定。 类固醇受体对基因表达的调节需要参与共同因素。 这些将通过遗传筛选来识别。 这些实验将共同研究类固醇受体的共同因素如何介导类固醇激素反应基因的细胞类型的特异性表达。 这项基础研究将有助于我们理解与肥胖，糖尿病和癌症等与人类疾病相关的激素信号传导的破坏。 这项工作也将是几位本科生和研究生参加研究的独特机会。 俄克拉荷马州的学生在科学领域的非农业培训方面几乎没有选择。 该项目提供的经验并不容易获得，它们补充了传统的讲座格式课程。 这些研究经验将继续使俄克拉荷马州的才华横溢的学生能够从事行业，医学和科学研究。