WERNERS PROTEIN BIOCHEMISTRY AND RIBOSOMAL DNA IN AGING

WERNERS 蛋白质生物化学和衰老过程中的核糖体 DNA

• 批准号: 2769277
• 负责人: F. Brad Johnson
• 金额: $ 10.11万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769277
• 关键词: DNA binding protein; DNA topoisomerases; SDS polyacrylamide gel electrophoresis; Werner's syndrome; age difference; aging; animal genetic material tag; enzyme activity; gel mobility shift assay; gene mutation; genetic recombination; genetic transcription; helicase; human genetic material tag; human tissue; laboratory mouse; molecular cloning; northern blottings; nuclear runoff assay; nucleic acid metabolism; nucleic acid structure; protein structure function; ribosomal DNA; southern blotting; thin layer chromatography

The candidate is M.D./Ph.D. who will have completed the clinical requirements of his residency in clinical pathology at Brigham and Women's Hospital prior to the proposed start date. He is committed to a career as a biomedical researcher in academic medicine, and has a particular interest in the biology of senescence. He has worked previously in the fields of molecular biology, the biochemistry of transcription and Drosophila developmental biology, and now wishes to learn more about experimental approaches to the study of aging. He also wishes to further develop the skills he will need to become an independent investigator. The proposed research will be carried out primarily in the laboratory of Dr. Leonard Guarente at M.I.T, who has engaged in detailed genetic and molecular investigations of aging in yeast for five years, and has expanded into studies in mouse and humans in the past two. Dr. Jeanne Wei, of the Harvard Division on Aging, will comentor the candidate, providing expertise on studies of aging in humans. The candidate will also participate in the regular activities of the Division on Aging. The candidate proposes two main investigations. First, to characterize the biochemical activities of the protein that is mutated in Werner's syndrome (WRN). The probable helicase activity of WRN will be defined and functional interactions with other proteins, including single stranded DNA binding proteins and topoisomerases, will be examined. Attempts will be made to define direct roles of WRN in simple recombination and transcription systems. The second part of the proposal is to examine the role of changes of ribosomal DNA (rDNA) metabolism in Werner's syndrome and in natural aging in humans and mice. Age-related changes in rDNA quantity, structure, and transcription in humans and mouse models will be examined. Finally, attempts will be made to determine the functional significance of these changes.

候选人是MD。博士他们将完成临床试验 他在布里格姆临床病理学的居住要求， 在拟议的开始日期之前，妇女医院。他致力 成为学术医学领域的生物医学研究员，并已 对衰老的生物学特别感兴趣。曾就职 以前在分子生物学领域， 转录和果蝇发育生物学，现在希望 了解更多关于衰老研究的实验方法。 他还希望进一步发展他将需要成为一个 独立调查员 拟议的研究将主要在实验室进行 麻省理工学院的伦纳德·瓜伦特博士， 对酵母老化的遗传和分子研究长达五年， 在过去的两年中，该研究已经扩展到小鼠和人类的研究。 博士来自哈佛老龄化部门的Jeanne Wei将对 候选人，提供人类衰老研究的专业知识。的 候选人还将参加该司的定期活动 关于衰老 候选人提出了两项主要调查。一是 表征突变的蛋白质的生物化学活性， 沃纳综合征（WRN）。WRN可能的解旋酶活性 将被定义并与其他蛋白质进行功能性相互作用， 包括单链DNA结合蛋白和拓扑异构酶， 将被审查。将努力界定以下方面的直接作用： 简单重组和转录系统中的WRN。第二 这项计划的一部分是研究核糖体变化的作用， Werner综合征和自然衰老中的DNA（rDNA）代谢 在人类和老鼠身上。rDNA数量，结构， 并将检查人和小鼠模型中的转录。 最后，将尝试确定函数意义 这些变化。