FTICR MASS SPECTRMETRY RESOURCE FOR BIOLOGICAL RESEARCH

介绍了太平洋西北国家实验室的质谱研究资源，用于支持生物医学研究的先进仪器方法的开发和应用。 该设施的核心技术研究工作将涉及基于电喷雾电离（ESI）-傅立叶变换离子回旋共振（FTICR）质谱的仪器方法的开发，用于生物聚合物的超灵敏表征。 对于较大的生物聚合物，FTICR具有极高的分辨率和精确的质量测量，可以进行更有效的鉴定，并提供更广泛的结构信息。 该资源将利用基于毛细管电泳的纳米级分离能力和微加工装置来处理非常小的样品。 与其他核心工作相结合，将提高FTICR的整体灵敏度和质量，该资源将使测量比传统仪器更敏感。 例如，这些能力将用于蛋白质组的全球测量，从而规避目前2-D凝胶技术的限制，并允许以比目前可能的更高的灵敏度快速研究复杂系统中的蛋白质表达。 该资源将利用现有的新仪器，包括具有两个完整光谱仪的高磁场（11.5特斯拉）FTICR，以及3.5和7特斯拉FTICR和其他质谱仪器。 该资源将利用能源部的大量投资，以及包括设备维护和独特的“合作实验室”研究环境在内的大量持续支持。该资源将向区域和国家生物研究合作者和用户提供其先进能力。 重要的生物医学合作努力将包括在单细胞水平上对神经化学过程进行独特的信息测量，对用其他方法没有有效研究的大蛋白质-蛋白质和蛋白质-DNA相互作用的研究，以及鉴定磷蛋白及其在T细胞中磷酸化的差异状态，T细胞致力于对改变的肽配体产生增殖或无反应性状态。

A Mass Spectrometry Research Resource at Pacific Northwest National Laboratory for the development and application of advanced instrumental methods in support of biomedical research is described. The facility's Core technological research efforts will involve the development of instrumental methods based upon electrospray ionization (ESI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry for the ultra-sensitive characterization of biopolymers. The extremely high resolution and accurate mass measurements feasible with FTICR for larger biopolymers allows more effective identification and provides more extensive structural information. The Resource will utilize nano-scale separation capabilities based upon capillary electrophoresis and micro-fabricated devices for the manipulation of very small samples. In combination with other Core efforts that will improve the overall sensitivity and quality of FTICR, the Resource will enable measurements that are orders of magnitude more sensitive than feasible with conventional instrumentation. These capabilities will be used, for example, for global measurements of proteomes that circumvent the limitations of present 2-D gel technology, and allow rapid studies of protein expression in complex systems with far greater sensitivity than currently possible. The Resource will exploit new instrumentation already available, including a high-magnetic-field (11.5 tesla) FTICR having two complete spectrometers, as well as 3.5 and 7 tesla FTICRs and other mass spectrometric instrumentation. The Resource will leverage a large investment by DOE, as well substantial on-going support that includes equipment maintenance and a unique "collaboratory" research environment. The Resource will serve to make its advanced capabilities available to regional and national collaborators and users in biological research. Important biomedical collaborative efforts will include uniquely informative measurements of neurochemical processes at the single cell level, studies of large protein-protein and protein-DNA interactions not effectively studied with other methods, and the identification of phosphoproteins and their differential state of phosphorylation in T cells committed to a proliferating or anergic state in response to altered peptide ligands.