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.

包括人类基因组计划在内的全球基因组倡议产生了大量信息，抛弃了新技术，并催化了新型生物学的出现，这种生物学试图从生物系统、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，用于对生物样品中的蛋白质表达谱进行定量和全局分析，包括生化和亚细胞部分、生物液体、细胞和组织。 因此，这项技术将把生物学研究的全球方法扩展到蛋白质分析，蛋白质是普遍构成生物系统的结构、功能和控制的分子。 该技术的基础是一类新型试剂，我们称之为同位素编码亲和标签。 分离后引入蛋白质中特定功能基团的标签既可作为分离标记蛋白质片段的配体，也可作为可进行质谱解卷积的定量代码。该计划具有三个显着特点，满足创新技术发展的要求。首先，该技术探索了定量蛋白质分析的新方法，有潜力成为蛋白质组学新兴领域的技术基础。 其次，该研究将由学术/工业合作伙伴组成的多学科团队进行。 此次合作预计将通过开发、商业化和支持所需的化学物质、仪器和软件作为成熟的集成产品来加速该技术的传播。 第三，该研究将在独特的研究环境中进行，即华盛顿大学新的定量系统生物学研究所。 该研究所的结构体现了一项技术从诞生到融入生物研究项目并支持大规模应用的演变。 该研究所还提供跨学科研究环境和学术/工业伙伴关系蓬勃发展所需的设施。一旦开发出来，这种技术将成为生物学家尝试从生物系统的功能、控制和机制方面解释基因组线性信息的重要工具。 应用于癌症研究时，该方法将允许定量测量和识别区分特定癌细胞和正常细胞的分子。 因此，该技术将极大地有助于分子诊断、癌症风险和预后评估以及对癌症分子基础的理解。