WERNERS PROTEIN BIOCHEMISTRY AND RIBOSOMAL DNA IN AGING

候选人是医学博士/博士，他将完成临床 他在布里格姆的临床病理学住院医师资格的要求 妇女医院在建议的开业日期之前。他全力以赴 成为一名学术医学领域的生物医学研究员，并拥有 对衰老生物学特别感兴趣。他曾经工作过 以前在分子生物学领域，生物化学 转录和果蝇发育生物学，现在希望 以了解更多关于衰老研究的实验方法。 他还希望进一步发展成为一名职业球员所需的技能 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，他参与了详细的 五年酵母老化的遗传学和分子研究， 在过去的两年里，它已经扩展到对老鼠和人类的研究。 哈佛大学老年部的珍妮·韦博士将主持 候选人，提供关于人类衰老研究的专业知识。这个 候选人还将参加该司的定期活动 关于年龄问题。这位候选人提出了两项主要调查。第一，要 描述突变后的蛋白质的生化活性 Werner综合征(WRN)。WRN可能的解旋酶活性 将被定义为与其他蛋白质的功能相互作用， 包括单链DNA结合蛋白和拓扑异构酶， 将会被检查。将尝试定义以下的直接角色 WRN在简单的重组和转录系统中。第二 该提案的一部分是研究核糖体变化的作用。 Werner综合征和自然衰老患者的DNA(RDNA)代谢 在人类和老鼠身上。与年龄相关的rDNA数量、结构、 我们还将研究人类和小鼠模型中的转录情况。 最后，将尝试确定其功能意义 这些变化。

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.