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Nuclear Hormone Receptor Regulation in C elegans

线虫的核激素受体调节

基本信息

批准号：
6731201
负责人：
Marc R Van Gilst
金额：
$ 9.48万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-04-01 至 2005-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6731201
关键词：
Caenorhabditis elegans chromatin gene induction /repression gene targeting genetic regulatory element genetic transcription green fluorescent proteins immunoprecipitation nuclear receptors receptor expression tissue /cell culture

项目摘要

DESCRIPTION (provided by applicant) Nuclear hormone receptors (NHRs) comprise a class of transcription factors that are involved in many biological processes, including dietary metabolism. Thus NHRs have proven to be attractive drug targets for the treatment of obesity and diabetes. The mechanisms by which NHRs function in living organisms are quite complex however, and many therapeutic approaches become ineffective due to drug resistance and undesirable side-effects. Through my work, I hope to enhance our understanding of how NHRs function in all aspects of development and homeostasis. This understanding would hopefully lead to the production of better NHR based therapies for diabetes, obesity, and other human maladies. My long-term strategy is to develop a system for characterizing NHR regulatory networks in vivo. In order to accomplish my goals I have chosen to use the roundworm C. elegans as a model organism for investigating NHRs. C. elegans provides several advantages for studying transcription factors in vivo, and for linking molecular functions to distinct physiological processes. I will observe and quantify NHR activity in live animals, and assess the contribution of regulatory factors to NHR activity. Additionally, I will use this system to discover the links between NHR function and physiological processes. In the period covered by this grant I will focus on adopting several skills that will be useful for setting up the system I described above. First, I will learn computer programming methods and chromatin immunoprecipitation techniques and adopt them to identify NHR target genes. Second, I will acquire expertise in worm physiology and anatomy and use this expertise to build GFP reporters with which I can visualize and quantify NHR regulation in vivo. Finally, I will learn to develop chemical extraction methods for the identification of small-molecule ligands that serve as regulators of C. elegans NHRs. The successful completion of the goals outlined in this proposal will greatly facilitate the initiation of an independent research lab that has the capacity to be immediately productive.

描述（由申请人提供）核激素受体（NHR）包括一类转录因子，参与许多生物过程，包括饮食代谢。因此 NHR已被证明是治疗肥胖症的有吸引力的药物靶标，糖尿病国家人权机构在生物体中发挥作用的机制相当复杂，然而，这是复杂的，并且许多治疗方法由于药物依赖性而变得无效。耐药性和不良副作用。我希望通过我的工作来提高我们的了解国家人权机构如何在发展的各个方面发挥作用，体内平衡这种理解有望导致产生更好的基于NHR的治疗糖尿病、肥胖症和其他人类疾病的方法。我的长期战略是开发一个系统来描述NHR监管网络在体内为了实现我的目标，我选择使用蛔虫角线虫作为模式生物研究NHRs。C. elegans 为研究体内转录因子提供了几个优点，将分子功能与不同的生理过程联系起来。我会观察量化活体动物的NHR活性，并评估 NHR活动的调节因素。此外，我将使用该系统发现NHR功能和生理过程之间的联系。在这段时间内，我将专注于采用几种技能这将有助于建立我上面描述的系统。首先我会学习计算机编程方法和染色质免疫沉淀技术并采用它们来鉴定NHR靶基因。第二，我将获得专业知识在蠕虫生理学和解剖学方面，并利用这些专业知识构建GFP报告基因我可以用它来观察和量化体内NHR的调节。最后要学习开发化学提取方法用于鉴定作为C. elegans NHRs.的成功完成本建议中概述的目标将大大促进建立一个独立的研究实验室，立即生产。