ISOTOPE CODED AFFINITY TAGS FOR QUANTITATIVE PROTEOMICS

用于定量蛋白质组学的同位素编码亲和标签

• 批准号: 6497962
• 负责人: Ruedi H. Aebersold
• 金额: $ 52.01万
• 依托单位: INSTITUTE FOR SYSTEMS BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-11 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6497962
• 关键词: T lymphocyte; affinity labeling; biotin; clone cells; computer system design /evaluation; deuterium; electrophoresis; gel electrophoresis; gene expression; high performance liquid chromatography; liquid chromatography; macromolecule; mass spectrometry; membrane proteins; method development; molecular oncology; proteomics; radionuclides; reagent /indicator

Global genome initiatives including the Human Genome Project have generated enormous amounts of information, spurned new technologies and catalyzed the emergence of a new type of biology which attempts to build biological knowledge from the global analysis of biological systems, pathways and cells. In this program we propose to develop a novel technology for the quantitative and global analysis of protein expression profiles in biological samples including biochemical and subcellular fractions, biological fluids, cells and tissues. Thus, this technology will extend the global approach to biological research to the analysis of proteins, the molecules that universally constitute the structure, function and control of biological systems. The basis of the technology is a new class of reagents we term isotope coded affinity tags. The tags which are introduced to specific functional groups in proteins post isolation serve as both, ligands for the isolation of tagged protein segments as well as a quantitative code which can be mass spectrometrically deconvoluted. The proposed program has three distinguishing features which satisfy the request for innovative technology development. First, the technology explores a new approach to quantitative protein analysis and has the potential to become the technical foundation of the emerging field of proteomics. Second, the research will be conducted by a multidisciplinary team constituted as an academic/industrial partnership. This partnership is expected to accelerate dissemination of the technology by developing, commercializing and supporting the required chemistries, instrumentation and software as mature, integrated products. Third, the research will be conducted in a unique research environment, the new Institute for Quantitative Systems Biology at the University of Washington. The structure of this institute embodies the evolution of a technology from its inception to the integration into biological research programs and to the support of large-scale applications. The Institute also provides the interdisciplinary research environment and the facilities required for the academic/industrial partnership to flourish. Once developed, such a technology will be an essential tool for biologists' attempts to interpret the linear information of genomes in terms of function, control and mechanisms of biological systems. Applied to cancer research the method will permit the quantitative measurement and identification of the molecules that distinguish a particular cancer cell from a normal cell. The technology will thus significantly contribute to the molecular diagnosis, the assessment of the cancer risk and prognosis, and the understanding of the molecular basis of cancer.

包括人类基因组项目在内的全球基因组倡议已经产生了大量信息，拒绝了新技术，并催化了一种新型生物学的出现，该生物学试图从对生物系统，途径和细胞的全球分析中建立生物学知识。在该计划中，我们建议开发一种新技术，用于对生物学样品（包括生化和亚细胞级分，生物流体，细胞和组织）的蛋白质表达谱的定量和全局分析。 因此，该技术将将全球生物学研究方法扩展到蛋白质分析，即普遍构成生物系统的结构，功能和控制的分子。 该技术的基础是我们称同位素编码的亲和力标签的新试剂类。 分离后蛋白质中引入特定官能团的标签既可以用作分离标记的蛋白质片段的配体，又可以作为质量光谱横向vol的定量代码。拟议的计划具有三个可满足创新技术开发要求的区别特征。首先，该技术探讨了一种新的定量蛋白质分析方法，并有可能成为新兴蛋白质组学领域的技术基础。 其次，该研究将由一个多学科团队作为学术/工业合作伙伴关系进行。 预计该合作伙伴关系将通过开发，商业化和支持所需的化学，仪器和软件作为成熟的集成产品来加速技术的传播。 第三，该研究将在华盛顿大学的新定量系统生物学研究所进行独特的研究环境中进行。 该研究所的结构体现了一项技术从其成立到整合到生物学研究计划和支持大规模应用的发展。 该研究所还提供跨学科的研究环境以及学术/工业伙伴关系蓬勃发展所需的设施。一旦开发，这种技术将是生物学家尝试以生物系统功能，控制和机制来解释基因组线性信息的重要工具。 应用于癌症研究，该方法将允许对区分特定癌细胞与正常细胞的分子进行定量测量和鉴定。 因此，该技术将显着有助于分子诊断，癌症风险和预后的评估以及对癌症分子基础的理解。