Acquisition of a LTQ Orbitrap XL ETD Hybrid FT Mass Spectrometer

描述（由申请人提供）：申请Thermo Scientific公司的LTQ Orbitrap XL ETDTM混合FT质谱计的资金，用于国防，疫苗开发以及了解化学毒性，激酶信号传导和疾病致病性的重要研究。蛋白质消化的液相色谱分离，特别是与敏感和非常精确的串联质谱相结合，全蛋白质精确测量与自上而下的蛋白质气相测序相结合，是亚利桑那大学现有的美国国立卫生研究院资助的研究人员非常需要的蛋白质组学能力。该仪器将为我们的LC-MS应用增加价值，特别是对于那些绝对需要增加肽测序的信心，因为片段离子的精确质量测量（~ 2ppm），使用ETD鉴定PTMs，鉴定更多高电荷交联肽，以及小蛋白质的全蛋白质量测量。该系统将加入亚利桑那大学亚利桑那蛋白质组学联盟现有的仪器基础设施。获得该仪器将大大提高我们的研究效率，对于支持该应用的nih资助的研究人员来说，这是至关重要的，他们过去都使用当前的仪器进行LC-MS，但现在需要高通量准确的蛋白质组学质谱仪。目前还没有这样的蛋白质组学系统存在，尽管各种各样的质谱分析可以在校园里进行。Thermo Scientific LTQ Orbitrap XL ETDTM混合FT质谱仪已被证明是非常可靠的蛋白质组学应用。美国国立卫生研究院资助的亚利桑那大学化学与生物化学系（科学医学院）、分子与细胞生物学（科学学院）、药理学与毒理学（药学院）、生理学（医学院）以及其他各种美国国立卫生研究院资助的外部用户支持购买该仪器。亚利桑那蛋白质组学协会还将为校园内需要其他特定用途的众多未成年用户提供仪器。使用这台升级后的仪器的战略研究重点将是(1)鉴定和表征太平洋西南区域生物防御和新发疾病卓越中心成员的混合物或纯化蛋白质中的蛋白质，(2)表征交联肽和蛋白质，以及(3)自上而下的小蛋白质研究。给出了制造商演示数据和我们的几个用户的数据，这些数据清楚地展示了该质谱仪的需求和实用性。亚利桑那大学的支持系统在经验丰富的人员、组织和管理能力以及使用记录方面存在，使得收购LTQ Orbitrap XL ETDTM混合FT质谱仪成为处理基于ms的研究和未来科学挑战的合理选择。

DESCRIPTION (provided by applicant): Funds are requested for a LTQ Orbitrap XL ETDTM hybrid FT mass spectrometer, from Thermo Scientific to be used in research important in national defense, vaccine development, and for understanding chemical toxicity, kinase signaling, and pathogenicity of disease. Liquid chromatography separations of protein digests, specifically coupled to sensitive and very accurate tandem mass spectrometry, and whole protein accurate measurements coupled to top-down protein gas-phase sequencing, are highly needed proteomics capabilities for existing NIH-funded investigators at the University of Arizona. This instrument will add value to our LC-MS applications, specifically for those that absolutely require increased confidence of peptide sequencing due to accurate mass measurements of fragment ions (~2 ppm), identification of PTMs using ETD, identification of more highly-charged cross-linked peptides, as well as whole protein mass measurements of small proteins. This system will join the existing instrumentation infrastructure of the Arizona Proteomics Consortium at the University of Arizona. Obtaining this instrument will greatly increase the productivity of our research, and it is critical for the NIH-funded investigators supporting this application, who have all performed LC-MS in the past using current instrumentation but who now have a need for a high-throughput accurate proteomics mass spectrometer. Currently no such proteomics system exists, despite the variety of mass spectrometric analyses that can be performed on campus. The Thermo Scientific LTQ Orbitrap XL ETDTM hybrid FT mass spectrometer has been shown to be extremely reliable for proteomics applications. Acquisition of this instrument is being supported by NIH-funded investigators at the University of Arizona from the Department of Chemistry and Biochemistry, (College of Science Medicine (College of Medicine), Molecular and Cellular Biology (College of Science), Pharmacology and Toxicology (College of Pharmacy), Physiology (College of Medicine), as well as by various other NIH-funded external users. The Arizona Proteomics Consortium will also make the instrument available for numerous minor users on campus who have a need for other such specific uses as proposed here. The strategic research areas of focus for use of this upgraded instrument will be (1) identification and characterization of proteins in mixtures or of purified proteins of members of the Pacific Southwest Regional Center for Excellence in Biodefense and Emerging Diseases, (2) characterization of cross-linked peptides and proteins, and (3) top-down investigations of small proteins. Manufacturer demonstration data and that from several of our users are presented which clearly showcase the need and utility for this mass spectrometer. The support system at the University of Arizona exists in terms of experienced personnel, organizational and management abilities and usage track record, making acquisition of the LTQ Orbitrap XL ETDTM hybrid FT mass spectrometer a logical choice to handle the MS-based research and scientific challenges of the future. PUBLIC HEALTH RELEVANCE: Protein identification using mass spectrometry relies heavily on the ability to obtain extremely accurate mass measurements. The requested instrument will greatly enhance our ability to do just that and to identify with greater confidence proteins important for national defense, vaccine development, and those important for increasing our understanding of chemical toxicity, protein signaling, and pathogenicity of disease. The requested mass spectrometer will fit into the fleet of environmentally proteomic tools and protocols available at the Arizona Proteomics Consortium, which is staffed by eight employees consisting of Ph.D, MS and BS-level scientists. In addition, the requested instrument will be used as a training tool, like all the rest of our hardware, for current and future undergraduate and graduate-level students actively engaging in health-related research.