THE STRUCTURE AND FUNCTION OF THE NOR 90K AUTOANTIGEN

NOR 90K 自身抗原的结构和功能

• 批准号: 3085620
• 负责人: ROBERT J KIPNIS
• 金额: $ 8.53万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085620
• 关键词: DNA; DNA footprinting; affinity chromatography; autoantigens; autoimmune disorder; autoradiography; bacteriophage lambda; electron microscopy; gene expression; molecular cloning; molecular pathology; nucleic acid probes; nucleic acid sequence; nucleolus; protein structure function; scleroderma; tissue /cell culture

I will seek to define the structure and function of the NOR 90K protein. This is a newly discovered component of the nucleolus and is present within the nucleolus-organizing-regions of metaphase chromosomes. I will use standard cloning methods to derive a full length cDNA for the gene that encodes this protein. That effort will provide information about the primary and possibly the secondary structure of this protein. It will also provide a useful probe for studies of the species and tissue distribution of the NOR 90K gene and the circumstances of its expression. In a separate approach, I will isolate the NOR 90K protein biochemically and examine its ability to bind to specific base sequence within DNA. I will also localize this protein at the level of resolution of the electron microscope. These studies should provide sufficient information so that hypotheses about the function of this protein can be developed and tested. In phase 2 of this program, I will turn my attention to more clinically related problems and seek to understand why the NOR 90K protein acts as an autoantigen in scleroderma. Through a rigorous series of basic course work, the research program outlined in this proposal, and the constant supervision of my mentors, I feel confident that this program will provide a sound foundation for a career in academic rheumatology.

我将寻求定义NOR 90K的结构和功能 蛋白质。 这是核仁的新发现的成分 并且存在于 中期染色体。 我将使用标准克隆方法 为编码该蛋白质的基因推导全长cDNA。 这项努力将提供有关主要的信息和 可能是该蛋白的二级结构。 它也会 为研究物种和组织提供了有用的探针 NOR 90K基因的分布及其情况 表达。 在另一种方法中，我将隔离90k 蛋白质生化并检查其与特定结合的能力 DNA中的基本序列。 我还将将此蛋白质定位在 电子显微镜的分辨率水平。 这些研究 应该提供足够的信息，以便假设有关 该蛋白质的功能可以开发和测试。 在第2阶段 在这个程序中，我将把注意力转移到更多相关的临床上 问题并试图理解为什么NOR 90K蛋白会起作用 硬皮病中的自动抗原。 通过一系列严格的基本 课程工作，本提案中概述的研究计划，以及 我的导师不断监督，我对此充满信心 计划将为学术职业提供合理的基础 风湿病。