GLUCOCORTICOID RECEPTOR--STRUCTURE AND FUNCTION

糖皮质激素受体——结构和功能

• 批准号: 2133804
• 负责人: MARK DANIELSEN
• 金额: $ 6.75万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2133804
• 关键词: DNA binding protein; affinity chromatography; androgens; cell transformation; chimeric proteins; clone cells; conformation; corticosteroid inhibitor; flow cytometry; genetic transcription; glucocorticoids; laboratory mouse; laboratory rabbit; molecular cloning; molecular site; mutant; nucleic acid sequence; polymerase chain reaction; progesterone; protein engineering; protein purification; protein sequence; protein structure function; receptor binding; site directed mutagenesis; steroid hormone receptor; tissue /cell culture; transfection; ubiquitin; western blottings

The candidate, Dr. Mark Danielsen, is a recently appointed Assistant Professor in this Department. The first year of his R01 was productive and he has begun to develop collaborations with other research groups both within and outside this University. The Department places a very strong emphasis on research and recognizes that younger faculty require support during their formative years if they are to develop a prestigious and well funded research program. Teaching/committee loads are light in the first year or two and then steadily increase. If an RCDA is awarded Department commitments should not exceed 10% of his time. At present 50% of his time is taken up with non-research activities, and this would undoubtedly increase in the absence of an RCDA. If an RCDA is awarded the Department will further support the candidate by providing funds for both personnel and supplies. This should enable Dr. Danielsen to develop a number of new projects and collaborations that are not funded by his current R01. This proposal focuses on the hormone binding domain of the glucocorticoid receptor (GR) and is designed to shed light on the following questions: 1) What are the structural determinants of the hormone binding site? 2) How does hormone binding activate the receptor? The problem will be approached in two ways. First, hybrid receptors will be made which are mainly GR but which have small regions of either the progesterone or androgen receptor hormone binding domain replacing the GR sequence. These receptors will be analyzed for their ability to bind to GR agonists and antagonists (including progesterone) and to androgens. When binding occurs, the ability of the hormone to activate receptor will be studied. The second approach is to select for cells in tissue culture that contain mutant receptors that have a) become hormone independent, or b) require reduced levels of hormone, or c) can be activated efficiently by compounds that are usually partial agonists and/or antagonists. These receptors will be characterized by cloning and sequencing. As a long term project the hormone binding domain of the GR and selected hybrids/mutants will be expressed in an overexpression system to produce sufficient protein for structural studies.

候选人马克·丹尼森博士是最近任命的助理