Acquisition of a high-throughput high mass accuracy MS for chromatin research

描述(由申请者提供)：本资助申请申请资助购买芬兰Thermo Electron制造的LTQ Orbitrap质谱仪。该仪器是一种独特的混合质谱仪，它结合了线性离子陷阱和Orbitrap质谱仪。该系统将配备ESI电离源和测量员LC系统。LTQ Orbitrap将由俄亥俄州立大学校园化学仪器中心的质谱学和蛋白质组学(MS&P)核心设施定位和管理。轨道诱捕器将填补俄亥俄州立大学在研究仪器方面缺失的一个关键领域。研究和服务仪器的组合能够高通量LC-MS/MS(LTQ)、需要高分辨率的复杂混合物的分子式确定(Q-TOF、FTMS)表征(FTMS)，甚至自上而下的蛋白质组学(FTMS)。然而，这些仪器都不具备获得LC-MS和LC-MS/MS高质量精度数据的能力，LTQ Orbitrap通过增加在LC时间尺度上执行准确的质量分配、高质量分辨率和多级MSN的能力，很好地补充了目前可用的仪器。本申请中描述的研究活动满足了主要用户的需求，他们寻求高分辨率和高质量精度的LC-MS和纳米LC-MS/MS来表征染色质修饰。研究人员来自俄亥俄州立大学医学院的核心用户群体。所有主要用户都明白，如此重要的资源不仅将满足他们的需要，而且将为俄亥俄州立大学更广泛的研究界做出巨大贡献。此外，CCIC MS设施被指定为俄亥俄州质谱学联盟的中心设施。该设施通过向联盟合作伙伴(以及中西部的其他大学和行业)提供先进的仪器来满足俄亥俄州MS用户的需求。因此，俄亥俄州质谱学社区的用户也可以使用该仪器。鉴于染色质结构在适当调节细胞生长和发育中的核心作用，以及它作为癌症表观遗传治疗靶点的潜力，研究小组有兴趣确定组蛋白修饰的特定位置和模式。由于组蛋白异构体的同位异构性和翻译后修饰的复杂模式，高分辨率质谱学对于组蛋白修饰的分析至关重要。

DESCRIPTION (provided by applicant): This grant application requests funding to purchase an LTQ Orbitrap mass spectrometer manufactured by Thermo Electron, Finnigan. This instrument is a unique hybrid mass spectrometer that combines a linear ion trap and an orbitrap mass analyzer. The system will come equipped with ESI ionization sources and the surveyor LC system. The LTQ Orbitrap will be located and administered by the Mass Spectrometry and Proteomics (MS&P) core facility in the Campus Chemical Instrument Center at Ohio State University. The orbitrap will fill a critical missing niche in research instrumentation at the Ohio State University. The combined collection of research and service instruments are capable of high-throughput LC-MS/MS (LTQ), molecular formula determination (Q-Tof, FTMS) characterization of complex mixtures that require high resolution (FTMS) and even top-down proteomics (FTMS). However none of the instruments possess the ability to obtain high mass accuracy data for LC-MS and LC-MS/MS. The LTQ Orbitrap nicely complements the currently available instrumentation by adding the ability to perform accurate mass assignments, high mass resolution and multistage MSn at LC time scales. The research activities described in this application address the needs of major users who seek the capabilities of high resolution and high mass accuracy LC-MS and nano-LC-MS/MS to characterize chromatin modifications. The researchers from a core group of users in the Medical School at the Ohio State University. It is understood by all major users that a resource of this importance will not only serve their needs but will contribute greatly to the broader research community at Ohio State. In addition, the CCIC MS facility is designated as the hub facility for the Ohio Mass Spectrometry Consortium. The facility serves the needs of Ohio MS users by making the advanced instrumentation available to the Consortium partners (and to other universities and industries in the Midwest). Thus the instrument will also be available to users in the Ohio Mass Spectrometry Community. Relevance Given the central role of chromatin structure in the proper regulation of cell growth and development, and its potential as a target for epigenetic therapies in cancer, the team of investigators is interested in determining the specific sites and patterns of histone modifications. High-resolution mass spectrometry is crucial to the analysis of histone modifications due to the isobaric nature of histone variants combined with the complex pattern of posttranslational modifications.