Molecular Buffering of Replication in Yeast

酵母复制的分子缓冲

• 批准号: 6834644
• 负责人: JOHN L HARTMAN
• 金额: $ 13.37万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6834644
• 关键词: DNA replication; Saccharomyces cerevisiae; cell cycle; enzyme activity; fungal genetics; gene deletion mutation; gene induction /repression; gene interaction; genetic polymorphism; genetic promoter element; microorganism culture; ribonucleotide reductase

DESCRIPTION: (provided by Applicant) This proposal is designed to provide John Hartman with the scientific expertise and career development for success in academic medicine and basic science. Dr. Hartman has completed the clinical year of his hematology fellowship at the University of Washington, and is in the second year of research fellowship at the Fred Hutchinson Cancer Research Center under guidance of his mentors, Lee Hartwell and Maynard Olson. During the next five years, Dr. Hartman plans to continue his studies of molecular buffering of the DNA replication apparatus in yeast. By these studies, Dr. Hartman aims to gain new insights into the initiating events in cancer. He will employ novel methodologies for genome-wide analysis in yeast to understand in more detail the molecular pathways that maintain replication fidelity, with a special focus on the impact of genetic variation on these pathways. Dr. Hartman will undertake coursework related to cancer biology and analysis of complex biologic traits to further attain his scientific research goals. FHCRC has many faculty members with shared interests, who are engaged in related studies. Accordingly, an advisory board has been assembled to facilitate Dr. Hartman's research and academic progress. Dr. Hartman's long-term career goal is to better understand human genetic diversity as it relates to health and disease, which is one of the initiatives of the human genome project. The research tools necessary to begin analyzing such biologic complexity are presently available and under rapid development. A global appreciation of the interplay between genetic variation and molecular homeostasis is fundamental to understanding the genetic architecture of complex traits, such as cancer. This proposal is to use, in combination, tetracycline-regulated gene expression and the set of over 4000 haploid yeast deletion strains to comprehensively and systematically identify all non- essential genes capable of buffering replication stress. Such a detailed analysis is currently possible only in isogenic yeast, but it will provide the scientific foundation to investigate the impact of naturally occurring genetic variation upon replication fidelity in humans. During the five years of this research, Dr. Hartman will gain insight into molecular principles of cellular homeostasis, as they relate to replication fidelity and cancer, and he will develop aptitude for genome analysis that will serve him well throughout his career as an independent research scientist.

描述：（由申请人提供）该建议旨在提供 约翰·哈特曼（John Hartman）拥有成功的科学专业知识和职业发展 学术医学和基础科学专业。 哈特曼博士完成了 他在华盛顿大学血液学研究金的临床年份 并在弗雷德·哈钦森（Fred Hutchinson Cancer）研究奖学金的第二年 在他的导师李·哈特威尔（Lee Hartwell）和梅纳德·奥尔森（Maynard Olson）的指导下，研究中心。 在接下来的五年中，哈特曼博士计划继续学习 酵母中DNA复制设备的分子缓冲。 通过这些 研究，Hartman博士旨在获得有关启动事件的新见解 癌症。 他将在酵母中采用新型方法进行全基因组分析 更详细地了解保持复制的分子途径 保真度，特别关注遗传变异对这些变异的影响 途径。 哈特曼博士将在癌症生物学和 分析复杂的生物学特征，以进一步获得他的科学研究 目标。 FHCRC有许多具有共同利益的教职员工 在相关研究中。 因此，咨询委员会已组装到 促进Hartman博士的研究和学业进步。 哈特曼博士的长期职业目标是更好地了解人类遗传 与健康和疾病有关的多样性，这是倡议之一 人类基因组项目。 开始分析所需的研究工具 这种生物复杂性目前可用，并且正在快速发展。 遗传变异与分子之间的相互作用的全球欣赏 稳态是理解遗传结构的基础 复杂的特征，例如癌症。 该建议是结合使用 四环素调节的基因表达和超过4000个单倍体酵母集 删除菌株以全面和系统地识别所有非 - 能够缓冲复制应力的必需基因。 这样的详细 目前只有在同生酵母中进行分析，但它将提供 科学基础，以研究自然发生的遗传的影响 人类复制保真度的变化。 在这五年中 研究，哈特曼博士将深入了解细胞的分子原理 稳态，与复制忠诚和癌症有关，他将 建立基因组分析的能力，可以在他的整个过程中为他服务 作为独立研究科学家的职业。