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: 6168646
• 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 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6168646
• 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.

候选人是医学博士。谁将完成临床测试