MEMBRANE PROTEOMICS OF BREAST CANCER CELL LINES

描述(由申请人提供)：我们的计划是建立一个P41研究资源，专注于为NIH支持的生物医学研究社区服务，开发和整合用于协作和服务研究的新蛋白质组技术，传播新技术，并培训科学家使用它们。该资源内的技术发展将有助于知名合作研究人员在微生物致病性和创伤研究、慢性毒性感染以及乳腺和黑色素瘤肿瘤学领域的努力取得重大进展。精确测量几乎所有表达的蛋白质及其修饰形式的水平的能力可以为细胞的分子性质、细胞信号通路和网络、细胞周期、细胞分化以及与人类健康和各种疾病状态的进展相关的其他过程提供新的见解。表征蛋白质复合体的能力补充了这一能力，并允许测试假设和定义生物系统的操作。该资源的主要目标是开发和应用一套完整的生物学方法、新的分析技术和相关的计算和信息学工具，以进行比目前可能的更快、更定量、更敏感和更全面的蛋白质组测量；并促进这些新技术向生物医学研究界的传播。我们计划的技术开发还旨在提供新的能力，用于表征蛋白质修饰和量化跨越六个数量级以上的蛋白质丰度。这些基本发展将得到1)高通量分离蛋白质复合体的能力，这是获得更好的蛋白质相互作用信息和测试蛋白质组假说所需的能力，以及2)计算和生物信息学工具，需要有效地提取数据并以统计上合理的质量措施可视化数据，以帮助发展新的生物学理解。资源技术开发旨在挑战蛋白质组学研究，合作是根据它们的科学和生物医学相关性以及它们从资源的能力中受益并挑战核心技术的能力而选择的。该资源将利用和扩展环境分子科学实验室目前已建立的大量能力，包括合作基础设施、综合和多学科的科学团队、独特的质谱学仪器以及一套强大的蛋白质组数据管理和分析工具。

DESCRIPTION (provided by applicant): Our plan is to establish a P41 Research Resource focused on serving the NIH-supported biomedical research community by developing and integrating new proteomic technologies for collaborative and service studies, disseminating the new technologies, and training scientists in their use. Technological developments within the Resource will contribute significant advances to the efforts of prominent collaborative researchers in the areas of microbial pathogenicity and trauma research, chronic virulent infections, and mammary and melanoma oncology. The ability to precisely measure levels of nearly all expressed proteins and their modified forms can provide new insights into the molecular nature of cells, cell signaling pathways and networks, the cell cycle, cellular differentiation, and other processes relevant to human health and to the progression of various disease states. The ability to characterize protein complexes complements this capability and allows hypotheses to be tested and the biological system operation to be defined. Primary objectives of the Resource are to develop and apply an integrated set of biological methods, new analytical technologies, and associated computational and informatics tools for much more rapid, quantitative, sensitive, and comprehensive proteomic measurements than presently possible; and to facilitate the dissemination of these new technologies to the biomedical research community. Our planned technological developments also aim at providing new capabilities for the characterization of protein modifications and the quantitation of protein abundances spanning more than six orders of magnitude. These fundamental developments will be augmented by 1) capabilities for high throughput isolation of protein complexes needed to obtain better information on protein interactions and to test proteomic hypotheses, and 2) computational and bio-informatics tools needed to effectively extract and visualize data with statistically sound measures of quality to aid in development of new biological understandings. Resource technology developments are directed at challenging proteomic investigations, in collaborations selected on the basis of their scientific and biomedical relevance, as well as their capacity to benefit from the Resource's capabilities and challenge the core technology. The Resource will leverage and extend the substantial capabilities already established in the Environmental Molecular Sciences Laboratory that presently include a collaboratory infrastructure, an integrated and multi-disciplinary scientific team, unique mass spectrometric instrumentation, and a powerful suite of proteome data management and analysis tools.