Comparative Mouse Genomics Centers Consortiun

比较小鼠基因组学中心联盟

• 批准号: 6825883
• 负责人: PETER J. STAMBROOK
• 金额: $ 1.08万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-10 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6825883
• 关键词: biomedical facility; cell cycle; functional /structural genomics; genetic susceptibility; laboratory mouse; neoplasm /cancer genetics; regulatory gene

DESCRIPTION (Taken from the Applicant?s Abstract) This application proposes to produce and analyze mice that have been engineered to express attenuated alleles of cell cycle regulatory genes. It is anticipated that such alleles exist in human populations, but manifest predominantly after environmental challenge. The cell cycle regulatory genes that will be targeted are those encoding members of the Cyclin D/Cdk4, Rb, P14ink6 complex, which plays a critical role in the passage of cells through the G1 phase of the cell cycle. Initial emphasis will be given to a cyclin D1 polymorphism that is known to predispose to hereditary non-polyposis colorectal cancer (HNPCC). This project will be directed by Dr. Knudsen who is expert in the biology of Rb and the Cyclin D/Cdk4 complex. A second project, to be directed by Dr. Yolanda Sanchez, focuses on the G2 checkpoint and the cell cycle regulatory gene, Chkl. Dr. Sanchez?s expertise is in yeast genetics as well as in the mechanisms governing transit of cells through G2 and M phases. Dr. Stambrook is the principal investigator of this grant and will direct a third project that will produce mice with attenuated alleles of the Polo kinase, Plk3. This kinase, like Chkl, has G2/M regulatory function and is responsive to DNA damage. The University of Cincinnati College of Medicine has made commitments to institutional core facilities, which include a mouse Transgenic Core and a mouse knockout core. This core was established and is directed by Dr. Tom Doetschman, who plays a key role in this proposal. Other established cores include a DNA synthesis and sequencing core directed by Dr. Joanna Groden, a member of our internal advisory committee, a comparative pathology core directed by Dr. Greg Boivin, and a biostatistics core. Three new integrated cores funded, in part, by the Howard Hughes Medical Institute, by the Dean of the medical school, and by the Children?s Hospital Research Foundation, are available. These include a DNA microarray core, a proteomics core, and a bioinformatics core. This application proposes to take advantage of these core facilities and to contribute the collective expertise of the investigators in furthering the understanding of the interactions between environmental challenge and variant cell cycle genes in the genesis of disease.

描述（摘自申请人的摘要） 该应用程序建议生产和分析已被 被设计用于表达细胞周期调节基因的减弱等位基因。它 预计此类等位基因存在于人类群体中，但明显 主要是在环境挑战之后。细胞周期调控基因 将针对的是那些编码 Cyclin D/Cdk4、Rb、 P14ink6 复合物，在细胞通过 细胞周期的G1期。最初重点将放在细胞周期蛋白 D1 上 已知易患遗传性非息肉病的多态性 结直肠癌（HNPCC）。该项目将由 Knudsen 博士指导，他 是 Rb 和 Cyclin D/Cdk4 复合物的生物学专家。一秒钟 由 Yolanda Sanchez 博士领导的项目重点关注 G2 检查站 和细胞周期调节基因 Chkl。桑切斯博士的专长是酵母 遗传学以及控制细胞通过 G2 转运的机制 和M相。 Stambrook 博士是这项资助的首席研究员 将指导第三个项目，该项目将产生具有减毒等位基因的小鼠 Polo 激酶，Plk3。该激酶与 Chkl 一样，具有 G2/M 调节功能 并且对 DNA 损伤有反应。辛辛那提大学学院 医学界对机构核心设施做出了承诺，其中包括 小鼠转基因核心和小鼠敲除核心。这个核心成立了 由 Tom Doetschman 博士领导，他在该提案中发挥了关键作用。 其他已建立的核心包括 DNA 合成和测序核心 作者：Joanna Groden 博士，我们的内部咨询委员会成员 由 Greg Boivin 博士指导的比较病理学核心和生物统计学 核。三个新的集成核心部分由霍华德休斯资助 医学院，由医学院院长和儿童医院负责 医院研究基金会，可用。其中包括 DNA 微阵列 核心、蛋白质组学核心和生物信息学核心。本申请提出 利用这些核心设施并集体做出贡献 调查人员的专业知识有助于进一步了解 环境挑战与变异细胞周期基因之间的相互作用 疾病的起源。