6500 QTrap Mass Spectrometer for Yale University

描述(申请人提供)：耶鲁大学W.M.凯克生物技术资源实验室的MS和蛋白质组学核心开发了一种最先进的有针对性的蛋白质组学工作流程，该工作流程利用一种新兴的基于质谱学的范例来验证和定量差异蛋白质表达，这为从临床样本中识别和确认蛋白质生物标志物提供了潜在的重要诊断工具。由于耶鲁大学研究人员迅速接受了这项技术，我们要求为AB SCIEX 6500 QTRAP混合型三重四极-线性离子陷阱质谱仪提供资金，该质谱仪将致力于满足快速增长的对多个预选蛋白质水平进行量化的需求。此外，我们还需要一个自动进样器和UPLC系统，即Waters Corporation制造的Nano ACQUITY UPLC系统，该系统是与MS连接所必需的，它将在MS分析之前提供自动样品处理和肽分离，从而能够对非常复杂的样品进行全天候连续分析。当要求的仪器与我们内部开发的目标蛋白质组服务相结合时，所产生的平台将使我们能够极大地扩展目标蛋白质组学服务，使它们能够支持由来自7个机构(耶鲁大学、维克森林、达特茅斯学院、芝加哥大学、巴塞罗那大学、蒙大拿大学和纽约大学)的27名研究人员指导的34个由NIH资助的项目，这些机构支持这一应用程序。这些研究人员建议利用我们有针对性的蛋白质组服务来推进以下方面的多样化生物医学研究：贫血、无菌性脑膜炎、肌萎缩侧索硬化症、神经元发育和退行性疾病(阿尔茨海默病、帕金森病、普恩疾病)、癌症(血管生成、乳头瘤病毒和黑色素瘤)、糖尿病、药物成瘾、心血管疾病、肺气肿、艾滋病毒、疟疾、骨质疏松症、钩端螺旋体病、突触传播和囊性纤维化。所要求的仪器将使现有的和新的有针对性的蛋白质组LC-MRM分析能够提供给29个国家的305个机构的461名耶鲁大学和574名非耶鲁大学(共1,035名)首席研究人员，他们在2012年使用了凯克实验室提供的服务。这项研究的进展将促进对如何最好地理解、预防、预测和治疗人类疾病的了解。所要求的6500 QTRAP质谱仪(MS)在耶鲁大学将是独一无二的，其他感兴趣的调查人员也可以使用，因为它位于一个核心设施，可以接受来自美国各地的样品，以及(当需要时)来自世界各地的仪器保持满负荷运行。因此，6500 QTRAP MS将对耶鲁大学和其他地方的生物医学研究做出重大贡献。

DESCRIPTION (provided by applicant): The Yale University, W.M. Keck Biotechnology Resource Laboratory's MS & Proteomics Core has developed a state-of-the-art targeted proteomics workflow that utilizes an emerging mass spectrometry based paradigm for validating and quantitating differential protein expression that provides a potentially important diagnostic tool for identification and confirmation of protein biomarkers from clinical samples. Due to rapid acceptance of this technology from Yale investigators, we are requesting funding for an AB SCIEX 6500 QTRAP hybrid triple quadrupole-linear ion trap mass spectrometer, which would be devoted to meeting the very rapidly increasing need for quantifying the levels of multiple preselected proteins. In addition, we are also requesting an automated sample injector and UPLC system, the nanoACQUITY UPLC manufactured by Waters Corporation, that is needed to interface with the MS and that will provide automated sample handing and peptide separation prior to MS analysis, thus enabling continuous 24/7 analysis of very complex samples. When the requested instrumentation is combined with our in-house developed targeted proteomic service, the resulting platform will enable us to greatly expand targeted proteomics services so they can support the 34 NIH-funded projects directed by 27 investigators from 7 Institutions (Yale University, Wake Forest, Dartmouth College, University of Chicago, Universitat de Barcelona, University of Montana, and New York University) that support this application. These investigators propose to use our targeted proteomic service to advance diverse biomedical research on: Anemia, Aseptic meningitis, Amyotrophic lateral sclerosis, Neuronal development and Degenerative (Alzheimer's, Parkinson's , Prion Diseases), Cancer (angiogenesis, papillomaviruses, and Melanoma), Diabetes, Drug Addiction, Cardiovascular disease, Emphysema, HIV, Malaria, Osteoporosis, Leptospirosis, Synaptic Transmission and Cystic Fibrosis. The requested instrumentation would enable existing and new targeted proteome LC-MRM analyses to be made available to the 461 Yale and 574 non-Yale (1,035 total) principal investigators at 305 institutions in 29 countries who used services provided by the Keck Laboratory in 2012. Progress in this research will advance knowledge of how best to understand, prevent, prognose, and treat human diseases. The requested 6500 QTRAP mass spectrometer (MS) would be unique at Yale University, and would be available to other interested investigators due to its placement in a core facility that accepts samples from across the U.S. and (when needed to keep its instrumentation operating at capacity) from around the world. Thus, the 6500 QTRAP MS would significantly contribute to biomedical research at Yale University and beyond.