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，重点是通过开发和整合新的蛋白质组学技术用于合作和服务研究，传播新技术，并培训科学家使用它们来服务于NIH支持的生物医学研究社区。该资源内的技术发展将为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杰出合作研究人员的努力做出重大贡献。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、细胞信号传导途径和网络、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。表征蛋白质复合物的能力补充了这种能力，并允许测试假设和定义生物系统操作。该资源的主要目标是开发和应用一套集成的生物学方法，新的分析技术，以及相关的计算和信息学工具，以实现比目前可能的更快速，定量，灵敏和全面的蛋白质组学测量;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定量蛋白质丰度，范围超过六个数量级。这些基本的发展将通过以下方面得到加强：1）获得更好的蛋白质相互作用信息和测试蛋白质组学假设所需的蛋白质复合物的高通量分离能力，以及2）有效提取和可视化数据所需的计算和生物信息学工具，这些数据具有统计学上合理的质量指标，以帮助发展新的生物学理解。资源技术开发的目标是挑战蛋白质组学研究，合作的选择是基于其科学和生物医学相关性，以及其受益于资源能力和挑战核心技术的能力。该资源将利用和扩展环境分子科学实验室已经建立的实质性能力，目前包括合作实验室基础设施，综合和多学科的科学团队，独特的质谱仪器，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.