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. ? ? ?
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