Thermo Electron LTQ Orbitrap XL - ETD Mass Spectrometer

描述(申请人提供)：本次NCRR共享仪器拨款申请的目的是获得资金，为弗吉尼亚大学医学院的W.M.Keck生物医学质谱仪实验室(MS Core)购买一台Thermo Electron Orbitrap XL-ETD质谱仪。该仪器将为复杂免疫沉淀(IP)、生物标志物和翻译后修饰(PTM)的高分辨率/质量准确度(HRMA)实验奠定基础。大学的目标是在这些领域提供更好的服务，为这些服务提供更大的容量，并为这些项目提供更快的周转时间。Orbitrap X-ETD将在现有仪器无法实现的情况下实现这些目标。MC Core是一个使用率很高的机构，它首先向UVA医学院提供与质谱学相关的专业知识和服务，然后向更广泛的UVA社区提供，最后向无法获得这些服务的外部机构提供。这一资源每年为100多个主要研究员实验室提供服务，项目范围从简单的质量控制(分子量测量)到复杂的混合物分析(生物标记物)。目前，更复杂的实验是在热电子LTQFT上进行的。该仪器已满负荷运行，而且MS Core只有25%的时间开销。该仪器剩余的时间用于细胞迁移联盟(U54 GM064346-07 Horwitz-PI)蛋白质组学部分的项目。目前在复杂混合物、生物标记物和PTMS中的项目使用LTQFT，但25%的时间利益不能为当前项目提供足够的资源，研究人员要么不得不等待几个月才能开始项目，要么被拒绝。新的Orbitrap将在微软核心的主要控制下提供HRMA资源，并允许调查人员及时开展项目。MS Core在质谱学和相关技术方面拥有13年以上的经验。我们在实验前和实验后的咨询经验，以及我们高素质的员工，使内部质谱学成为我们研究人员的首选。有了新的Orbitrap，我们作为中等吞吐量设备的使命将在几个研究人员要求更多的重要领域完成：1)IP或细胞室纯化的复杂混合物分析，2)复杂混合物的PTM分析(要求最多的-磷酸化、泛素化和甲基化)，以及3)复杂临床液体的生物标记物分析。与公众健康相关：Thermo Electron Orbitrap XL-ETD质谱仪将用于执行需要高分辨率和质量精度的蛋白质组学实验--复杂混合物、翻译后修饰、生物标志物等。这些类型的实验研究范围从基础细胞控制到癌症再到传染病。NIH对拟议项目的资助(以及后来的描述)明确将这些项目确立为对公共卫生问题的研究，这些公共卫生问题需要由高度合格和成功的质谱学核心操作的特定类型的仪器。弗吉尼亚大学医学院的W.M.凯克生物医学质谱学实验室是一个长期建立的资源核心，拥有高素质的人员，他们与NIH资助的研究人员一起工作了13年多，这些研究人员建立了生物学和医学方面的研究项目。购买这一工具对他们继续取得成功至关重要。

DESCRIPTION (provided by applicant): The objective of this NCRR Shared Instrument Grant application is to obtain funding to purchase a Thermo Electron Orbitrap XL-ETD mass spectrometer for the W.M. Keck Biomedical Mass Spectrometry Lab (MS Core) at the University of Virginia's School of Medicine. This instrument will be the foundation of high resolution/mass accuracy (HRMA) experiments in complex immunoprecipitation (IPs), biomarkers and post-translational modifications (PTMs). The goals of the University are to provide enhanced service in these areas, to provide higher capacity for these services, and to provide faster turnaround time for these projects. The Orbitrap X-ETD will meet these goals where existing instrumentation cannot. The MC Core is a heavily used facility providing mass spectrometry related expertise and services first to the UVA School of Medicine, then to the broader UVA community and finally to external institutions that do not have access to these services. This resource serves over 100 principle investigator labs per year in a wide variety of projects ranging from simple quality control (molecular weight measurements) to complex mixture analysis (biomarkers). At present the more complex experiments are run on a Thermo Electron LTQFT. This instrument is at full capacity and additionally the MS Core has only a 25% time interest. The remainder of this instrument's time is taken by projects for the proteomics section of the Cell Migration Consortium (U54 GM064346- 07 Horwitz -PI). Current projects in complex mixtures, biomarkers and PTMs utilize the LTQFT, but a 25% time interest does not provide enough resource for current projects and investigators either have to wait months to begin projects or be turned away. The new Orbitrap will provide an HRMA resource under primary control of the MS Core and allow investigators to pursue projects in a timely fashion. The MS Core has over 13 years experience in mass spectrometry and allied techniques. Our experience in consultation, both pre- and post-experiment, and our highly qualified staff make in-house mass spectrometry the preferred option for our investigators. With the new Orbitrap, our mission as a medium throughput facility will be fulfilled in several important areas that investigators are demanding more access to: 1) complex mixture analysis of IPs or cellular compartment purifications, 2) PTM analysis from complex mixtures (most requested - phosphorylation, ubiquitination, and methylation), and 3) biomarker analysis from complex clinical fluids. PUBLIC HEALTH RELEVANCE: The Thermo Electron Orbitrap XL-ETD mass spectrometer will be used to perform proteomics experiments that require high resolution and mass accuracy - complex mixtures, post-translational modifications, biomarkers, etc. These types of experimental studies range from fundamental cell control to cancer to infectious diseases. The NIH funding (and later descriptions) for the proposed projects clearly establishes these projects as research into public health issues that need a specific type of instrument operated by a highly qualified and successful mass spectrometry core. The W.M. Keck Biomedical Mass Spectrometry Lab at the University of Virginia's School of Medicine is a long established resource core with highly qualified personnel who have worked for over thirteen years with NIH funded investigators who have established research programs in biology and medicine. The purchase of this instrument is critical to their continued success.