Mechanisms of Response to GnRH Receptor Signaling

GnRH 受体信号传导的反应机制

• 批准号: 6935806
• 负责人: Mark Andrew Lawson
• 金额: $ 10.42万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-11 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6935806
• 关键词: RNA binding protein; biological signal transduction; cell line; complementary DNA; gene expression; genetic regulation; genetic transcription; genetic translation; genetically modified animals; gonadotropin releasing factor; hormone receptor; hormone regulation /control mechanism; laboratory mouse; messenger RNA; microarray technology; northern blottings; polymerase chain reaction; protein tyrosine kinase; radioimmunoassay; tissue /cell culture

DESCRIPTION (provided by applicant): The candidate has a broad training background in molecular biology and in animal model systems for the study of gene expression and endocrinology, including transgenic mice, rats, and hamsters. The candidate has training in all molecular biology techniques and has published manuscripts utilizing them. The training background includes virology, cellular and molecular biology, analysis of DNA-protein and protein- protein interactions, gene transcription, mRNA translation, and signal transduction. In vivo techniques include the creation and analysis of transgenic mice, tissue and organ analysis of mice, rats and hamsters, hormone replacement, dose-response assay paradigms, minor surgical procedures, immunohistochemistry, organotypic culture. Past awards include an independent R03 award and three prestigious postdoctoral fellowships. The environment provides an exceptional atmosphere for career development and further training. The candidate is a member of a U54 center, serving as a project co- investigator, and was recently awarded an R0l. He interacts with both basic science and clinical research faculty in his and other departments. His department has committed laboratory space in a modern, well equipped six year old facility, and he will move to a new expanded facility, that will open in 2003. The candidate's immediate goals are to increase laboratory personnel, to meet the scientific goals set out in the current R0l in support of renewal of that award, to initiate new research projects with the aim of supporting a successful application for a second R0l, and to achieve promotion to a tenured Associate Professor in the approximate time frame of this award. Although the candidate seeks relief from formal teaching and administrative duties normally required for progression to a tenured appointment, the candidate has a strong desire to provide an excellent training environment for graduate and postdoctoral level students. The candidate also seeks relief of salary burden on his current funding to support new laboratory personnel. The candidate proposes to initiate studies on the effects of pulsatile gonadotropin- releasing hormone on the translational and transcriptional regulation of gene expression. The candidate presents the hypothesis that releasing hormone modulates both transcriptional and non-transcriptional changes in gene expression and cell metabolism, and therefore regulates both short term and long term changes in gene transcription and mRNA utilization. Expanded aims are directed at understanding the modulation of pulsatile hormone stimulation by other endocrine effectors, such as insulin, growth factors, and gonadal steroids. Techniques to be applied to this problem include the use of the gonadotrope cell lines and primary pituitary cells for in a perifusion system, allowing the manipulation of the pulsatile regime. Isolation of actively translated and total mRNA from treated and control cells will allow identification and quantification of global changes in gene expression.

描述（由申请人提供）：候选人在分子生物学和动物模型系统方面拥有广泛的培训背景，用于研究 基因表达和内分泌学，包括转基因小鼠、大鼠和 仓鼠。候选人接受过所有分子生物学技术的培训，并且 已发表利用它们的手稿。培训背景包括 病毒学、细胞和分子生物学、DNA-蛋白质和蛋白质-分析 蛋白质相互作用、基因转录、mRNA 翻译和信号 转导。体内技术包括创建和分析 转基因小鼠，小鼠、大鼠和仓鼠的组织和器官分析，激素 替代、剂量反应测定范例、小型外科手术、 免疫组织化学，器官型培养。过去的奖项包括独立 R03 奖和三项著名的博士后奖学金。环境 为职业发展和进一步发展提供了良好的氛围 训练。该候选人是U54中心的成员，担任项目合作者 研究员，最近被授予 R0l。他与两个基本的交互 他和其他部门的科学和临床研究教师。他的 部门已在现代化、设备齐全的六年内投入了实验室空间 旧设施，他将搬到一个新的扩建设施，该设施将于 2003.候选人的近期目标是增加实验室人员， 满足当前 R0l 中规定的科学目标，以支持更新 该奖项旨在启动新的研究项目，旨在支持 成功申请第二个R0l，并晋升终身教授 副教授在该奖项的大致时间范围内。虽然 候选人通常寻求免除正式教学和行政职责 晋升为终身职位所需的候选人具有很强的能力 希望为毕业生提供良好的培养环境 博士后级别的学生。候选人还寻求减轻工资负担 关于他目前用于支持新实验室人员的资金。候选人 提议开始研究脉动促性腺激素的影响 释放激素对基因翻译和转录调控的影响 表达。候选人提出了释放激素的假设 调节基因的转录和非转录变化 表达和细胞代谢，因此调节短期和 基因转录和 mRNA 利用的长期变化。扩大目标 旨在了解脉动激素刺激的调节 其他内分泌效应物，如胰岛素、生长因子和性腺 类固醇。解决这个问题的技术包括使用 用于灌注系统的促性腺激素细胞系和原代垂体细胞， 允许操纵脉动状态。主动隔离 来自处理细胞和对照细胞的翻译和总 mRNA 将允许 基因表达的全局变化的识别和量化。