Orbitrap Fusion Lumos ETD with IRMPD for UM Chemistry MS Facility Expansion

Orbitrap Fusion Lumos ETD 与 IRMPD 用于 UM 化学 MS 设施扩建

• 批准号: 9075552
• 负责人: KRISTINA HAKANSSON
• 金额: $ 109.52万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9075552
• 关键词: Agreement; Arts; Biomedical Research; Chemistry; Cost Sharing; Custom; Disease; Dissociation; Doctor of Philosophy; Electron Transport; Funding; Generations; Housing; Ions; Lipids; Literature; Maintenance; Manufacturer Name; Marketing; Mass Spectrum Analysis; Methodology; Michigan; Minor; Multiprotein Complexes; Natural Products; Pathway interactions; Peptides; Persons; Post-Translational Protein Processing; Preparation; Productivity; Proteins; Proteomics; Qualifying; Records; Research Infrastructure; Research Personnel; Research Project Grants; Science; Services; TNFRSF5 gene; Techniques; Technology; Time; United States National Institutes of Health; Universities; Wages; college; cost; crosslink; improved; instrument; instrumentation; mass spectrometer; operation; programs

 DESCRIPTION (provided by applicant): This application to the NIH high end instrumentation program requests an Orbitrap Fusion Lumos with electron transfer dissociation (ETD); a new generation Orbitrap Tribrid mass spectrometer to be released on the market immediately after the proposal deadline. Through a non-disclosure agreement (expiring May 31, 2015), we have obtained a quote for this game-changing instrument for proteomic analysis, including 5-fold sensitivity improvement and 40% higher ETD efficiency compared with the current state-of-the-art Orbitrap Fusion Tribrid. With the assistance of the manufacturer (Thermo Fisher Scientific) we seek to custom fit this instrument with infrared multiphoton dissociation (IRMPD). The sought new generation Orbitrap Tribrid is further capable of precursor ion selection down to 0.4 amu without analyte loss for greatly improved selectivity. The proposed users (7 major, 9 minor) represent six different University of Michigan (UM) Departments, all in close geographical proximity on the UM central campus, which is entirely void of infrastructure for shared proteomic analysis. UM has strong track records in both biomedical research and mass spectrometry (MS) technologies that enable breakthroughs in basic biomedical and disease science. The proposed users focus on analyzing disease- associated multiprotein complexes through crosslinking/MS, quantifying disease-associated changes in protein posttranslational modifications, small volume trace analysis of peptides, lipids, and metabolites, as well as discovery and mechanistic/structural interrogation of natural product biosynthetic pathways. The described, NIH- funded (17 R01, three R37, one DP2, two U01, and one P50 grant) research projects will leverage the unique group of world-class MS experts at UM to develop/extend the utility of the Orbitrap Fusion Lumos, including the custom IRMPD capability, thus providing additional benefits in the form of new methodologies and techniques. The proposed instrument will be housed within an expanded MS facility, being developed into an MS Center of Excellence, within the UM Department of Chemistry. This facility is highly used by researchers throughout the region, but still operates with out-of-date instruments that range between 20 to 40 years old, and is thus in desperate need of the upgrade described in this proposal. Operation and maintenance of the instrument will be performed both by existing highly qualified staff in the Chemistry Department MS facility, but also by a new dedicated PhD-level staff person funded by the College of Literature, Science and the Arts (LSA), representing a total five year staff commitment of ~$1,000,000. In addition, various UM units have provided cost sharing for two years of service for the instrument (in addition to the year one warranty), after which time we expect that instrument recharge costs from major/minor users will support instrument operations within the Chemistry MS Facility, including contributions to partial funding (~60%) of the Facility staff. The remaining 40% of staff salaries will continue to be covered by LSA. Furthermore, UM LSA has agreed to renovate the existing MS facility space in preparation for the requested Orbitrap Fusion Lumos to maximize its productivity and use.

 描述（由申请人提供）：NIH高端仪器项目的本申请要求使用具有电子转移解离（ETD）功能的Orbitrap Fusion Lumos;新一代Orbitrap Tribrid质谱仪将在提案截止日期后立即上市。通过保密协议（2015年5月31日到期），我们获得了这款改变游戏规则的蛋白质组分析仪器的报价，包括与当前最先进的Orbitrap Fusion Tribrid相比，灵敏度提高了5倍，ETD效率提高了40%。在制造商（Thermo Fisher Scientific）的帮助下，我们寻求定制适合该仪器的红外多光子解离（IRMPD）。所寻求的新一代Orbitrap Tribrid还能够选择低至0.4 amu的前体离子，而不会损失分析物，从而大大提高了选择性。拟议的用户（7个主要，9个次要）代表六个不同的密歇根大学（UM）部门，所有这些部门都在UM中央校园的地理位置非常接近，这是完全没有基础设施的共享蛋白质组学分析。UM在生物医学研究和质谱（MS）技术方面都有很好的记录，这些技术使基础生物医学和疾病科学取得突破。建议的用户专注于通过交联/MS分析疾病相关的多蛋白复合物，量化蛋白质翻译后修饰中的疾病相关变化，肽，脂质和代谢物的小体积痕量分析，以及天然产物生物合成途径的发现和机制/结构询问。所描述的NIH资助的研究项目（17个R01，3个R37，1个DP2，2个U01和1个P50资助）将利用UM独特的世界级MS专家组来开发/扩展Orbitrap Fusion Lumos的实用性，包括自定义IRMPD功能，从而以新方法和技术的形式提供额外的好处。拟议的仪器将被安置在一个扩大的MS设施，正在发展成为一个卓越的MS中心，在化学的UM部门。该设施被整个区域的研究人员大量使用，但仍然使用20至40年前的过时仪器，因此迫切需要进行本提案所述的升级。该仪器的操作和维护将由化学系MS设施中现有的高素质工作人员进行，但也由文学、科学和艺术学院（LSA）资助的新的专门博士级工作人员进行，这意味着五年的工作人员承诺总额约为1，000，000美元。此外，各UM单位为仪器提供了两年服务的成本分摊（除第一年保修外），之后，我们预计主要/次要用户的仪器充电成本将支持化学MS设施内的仪器操作，包括对设施部分资金（约60%）的贡献 工作人员其余40%的工作人员薪金将继续由生活津贴支付。此外，UM LSA已同意翻新现有的MS设施空间，为所要求的Orbitrap Fusion Lumos做准备，以最大限度地提高其生产力和使用率。