5500 QTrap Mass Spectrometer for Yale University, Keck Laboratory

描述（由申请人提供）：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最先进的蛋白质组学技术，以最大限度地支持“从实验室到临床的研究”。这项名为靶向蛋白质组学的新服务利用了一种新兴的基于质谱的范式，用于验证、定量并可能生成一种新的诊断工具，用于从临床样本中识别和确认蛋白质生物标志物。由于耶鲁大学的研究人员迅速接受了这项技术，我们正在申请资助一个混合三重四极线性离子阱质谱仪，5500 QTRAP由应用生物系统公司制造，这将致力于满足快速增长的需求，定量多种预选蛋白质的水平。此外，我们还需要一个自动进样器和HPLC系统，即沃茨公司生产的nanoACQUITY UPLC，该系统需要与MS连接，并在MS分析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连续24/7分析。当所要求的仪器与我们内部开发的靶向蛋白质组学服务相结合时，所产生的平台将使我们能够扩展靶向蛋白质组学，并支持由21名研究人员指导的29个NIH资助的项目。这些研究人员建议使用我们的靶向蛋白质组学服务来推进各种生物医学研究：癌症（血管生成，乳头状瘤病毒和黑色素瘤），糖尿病，药物成瘾，神经元发育，心血管疾病，自闭症，流感，突触传递，慢性肾病，药物成瘾，Spitzoid肿瘤和唐氏综合征。两个主要的用户，理查德利夫顿（NHLBI蛋白质组学中心）和安格斯奈恩（NIDA神经蛋白质组学中心），将与我们的中心合作，以追求他们在肾脏疾病和药物成瘾和抑郁症的研究应用，同时也在生物技术研究合作，旨在进一步推进我们非常有前途的靶向蛋白质组学技术。这项工作将有助于快速开发新的靶向蛋白质组学服务，这些服务将提供给凯克实验室的所有其他研究贡献者和用户。这项研究的进展将促进如何最好地理解，预防和治疗人类疾病的知识。所要求的5500 QTRAP质谱仪（MS）将是耶鲁大学独有的，并将提供给其他感兴趣的研究人员，因为它放置在一个核心设施中，接受来自美国各地的样品。因此，5500 QTRAP MS将为耶鲁大学及其他地区的生物医学研究做出重大贡献。 公共卫生相关性：如果这笔赠款得到资助，所要求的5500 QTRAP质谱仪将为生物医学研究做出独特和实质性的贡献，这将扩展到研究许多疾病的基本机制的研究人员，包括糖尿病，药物滥用，流感，癌症，肾脏疾病，自闭症，高血压和唐氏综合症。

DESCRIPTION (provided by applicant): The Yale University, W.M. Keck Biotechnology Resource Laboratory's MS & Proteomics Core has developed a state-of-the-art proteomic technology to maximally support "Bench-to-Bedside Research". This new service entitled targeted proteomics utilizes an emerging mass spectrometry based paradigm for validating, quantitating, and potentially generating a new 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 a hybrid triple quadrupole-linear ion trap mass spectrometer, 5500 QTRAP manufactured by Applied Biosystems, 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 HPLC 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 expand targeted proteomics and support the 29 NIH-funded projects directed by 21 investigators in this proposal. These investigators propose to use our targeted proteomic service to advance diverse biomedical research on: Cancer (angiogenesis, papillomaviruses, and Melanoma), Diabetes, Drug Addiction, Neuronal Development, Cardiovascular disease, Autism, Influenza, Synaptic Transmission, Chronic Kidney Disease, Drug Addiction, Spitzoid neoplasms, and Down syndrome. Two of the major users, Richard Lifton (NHLBI Proteomics Center) and Angus Nairn (NIDA Neuroproteomics Center), will collaborate with our center to pursue their research applications in renal disease and in drug addiction and depression while also collaborating on biotechnology research directed at further advancing our highly promising targeted proteomic technologies. This effort will then assist in rapidly developing new targeted proteomic services that will be made available to all other research contributors and users of the Keck Lab. Progress in this research will advance knowledge of how best to understand, prevent, and treat human diseases. The requested 5500 QTRAP mass spectrometer (MS) would be unique to 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 5500 QTRAP MS would significantly contribute to biomedical research at Yale University and beyond. PUBLIC HEALTH RELEVANCE: If this grant is funded, the requested 5500 QTRAP mass spectrometer would make a unique and substantial contribution to biomedical research that would extend to investigators studying fundamental mechanisms of many diseases, including diabetes, substance abuse, influenza, cancer, renal diseases, autism, hypertension, and Down syndrome.