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

描述（由申请人提供）：本资助申请要求资助购买由Thermo Electron，Finnigan制造的LTQ Orbitrap质谱仪。该仪器是一种独特的混合质谱仪，结合了线性离子阱和轨道阱质量分析仪。该系统将配备ESI电离源和Surveyor LC系统。LTQ Orbitrap将位于俄亥俄州州立大学校园化学仪器中心的质谱和蛋白质组学（MS&P）核心设施并由其管理。轨道阱将填补俄亥俄州州立大学研究仪器中的一个关键空缺。研究和服务仪器的组合能够进行高通量LC-MS/MS（LTQ）、分子式测定（Q-Tof，FTMS）、需要高分辨率的复杂混合物表征（FTMS），甚至自上而下的蛋白质组学（FTMS）。然而，没有一种仪器能够获得LC-MS和LC-MS/MS的高质量准确度数据。LTQ Orbitrap通过增加在LC时间尺度上执行准确质量分配、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寻求高分辨率和高质量准确度LC-MS和nano-LC-MS/MS表征染色质修饰的主要用户的需求。研究人员来自俄亥俄州州立大学医学院的一个核心用户群体。所有主要用户都明白，这种重要性的资源不仅能满足他们的需求，而且将大大有助于俄亥俄州更广泛的研究界。此外，CCIC MS设施被指定为俄亥俄州质谱联盟的中心设施。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，该仪器也将提供给用户在俄亥俄州质谱社区。鉴于染色质结构在细胞生长和发育的适当调节中的核心作用，以及其作为癌症表观遗传疗法靶点的潜力，研究人员团队对确定组蛋白修饰的特定位点和模式感兴趣。由于组蛋白变体的同量异序性质和复杂的翻译后修饰模式，高分辨率质谱对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.