Molecular Buffering of Replication in Yeast

酵母复制的分子缓冲

• 批准号: 6689967
• 负责人: JOHN L HARTMAN
• 金额: $ 13.37万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 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 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6689967
• 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）该提案旨在提供 约翰·哈特曼 (John Hartman) 凭借科学专业知识和成功的职业发展 在学术医学和基础科学领域。 哈特曼博士已完成 他在华盛顿大学获得血液学奖学金的临床年， 现在是 Fred Hutchinson 癌症研究中心的第二年 研究中心在他的导师 Lee Hartwell 和 Maynard Olson 的指导下。 在接下来的五年中，哈特曼博士计划继续他的研究 酵母 DNA 复制装置的分子缓冲。 通过这些 哈特曼博士的研究旨在获得对引发事件的新见解 癌症。 他将采用新颖的方法进行酵母全基因组分析 更详细地了解维持复制的分子途径 保真度，特别关注遗传变异对这些的影响 途径。 哈特曼博士将承担与癌症生物学和 分析复杂的生物特征以进一步完成他的科学研究 目标。 FHCRC 拥有许多志同道合的教职人员，他们积极参与 在相关研究中。 据此，成立了一个咨询委员会 促进哈特曼博士的研究和学术进步。 哈特曼博士的长期职业目标是更好地了解人类遗传 与健康和疾病相关的多样性，这是倡议之一 人类基因组计划的一部分。 开始分析所需的研究工具 这种生物复杂性目前已经存在并正在快速开发中。 全球对遗传变异和分子之间相互作用的认识 体内平衡是理解遗传结构的基础 复杂的特征，例如癌症。 该建议将结合使用， 四环素调节的基因表达和超过 4000 个单倍体酵母的集合 删除菌株以全面、系统地识别所有非 能够缓冲复制压力的必需基因。 这么详细的 目前只能在同基因酵母中进行分析，但它将提供 研究自然发生的遗传影响的科学基础 人类复制保真度的变化。 在这五年的时间里 通过研究，哈特曼博士将深入了解细胞的分子原理 稳态，因为它们与复制保真度和癌症有关，他将 培养基因组分析的能力，这将在他的整个一生中为他提供良好的帮助 作为一名独立研究科学家的职业生涯。