Acquisition of triple quadrupole mass spectrometer for quantitative proteomics

描述(申请人提供)：本申请的目的是从Thermo Science获得一台质谱仪，特别是TSQ Vantage三级四极仪器。TSQ Vantage具有独特的能力来支持正在进行的研究，这些研究调查各种医学疾病的病理生理途径，以及正在开发新疗法的计划。该仪器将由美国国立卫生研究院资助的主要位于宾夕法尼亚大学的翻译研究实验室(TRL)的10名研究人员专门用于定量蛋白质组应用。由这些研究人员发起的正在进行的项目利用基因组发现、生化和分子方法来发现感兴趣的蛋白质、翻译后修饰和执行生物功能的蛋白质网络。这些项目中的大多数已经超过了发现阶段，并且已经确定了特定和实用的蛋白质和多肽靶标。这些项目的关键下一步是通过量化各种疾病或治疗中出现的蛋白质和多肽的变化来深入探索这些发现。由于这些方法缺乏灵敏度、特异性和/或高通量，典型的基于抗体的Western印迹、ELISA法或甚至现有的线性离子陷质谱计不能实现这一目标。靶向多肽定量是一种高度选择性和灵敏的方法学方法，用于定量评价蛋白质和蛋白质网络的动态变化以及验证和利用生物标志物。为了实现这一目标，国际标准化组织和拟议仪器的使用者已经开发和建立了使用稳定同位素标记的多肽、蛋白质组和多反应监测(MRM)/质谱仪(MS)工作流程的方法，用于对人体样本以及动物和细胞模型系统中的蛋白质进行定量。TSQ Vantage单元(Thermo-Science)与Eksigent Nano 2DLC相结合，自2010年9月以来一直在TRL中运行，将以宾夕法尼亚大学支持的租约保留到2013年3月。我们计划收购这个生产率极高的部门。张奎·哈恩，医学博士，博士，作为私人助理，将全面负责设备。领导层将由韩昌奎(音译)、医学博士和伊恩·布莱尔(Ian Blair)平分。韩昌奎和布莱尔将担任S的联合私人助理。韩长奎将专注于业务方面，布莱尔将提供科学监督。

DESCRIPTION (provided by applicant): The purpose of this application is to acquire a mass spectrometer, specifically the TSQ Vantage Triple Stage Quadrupole instrument from Thermo Scientific. The TSQ Vantage has unique capabilities to support ongoing studies that investigate pathophysiological pathways of diverse medical illnesses as well as programs that are developing novel therapeutics. This instrument will be used exclusively for quantitative proteomic applications by 10 NIH funded investigators located primarily at the Translational Research Laboratories (TRL) in the University of Pennsylvania. Ongoing projects initiated by these investigators have employed genomic discovery, biochemical, and molecular approaches to discover proteins of interest, posttranslational modifications, and protein networks that execute biological functions. The majority of these projects have advanced past the stages of discovery and specific and practical protein and peptide targets have been identified. A critical next step for these projects is to explore these discoveries in depth by quantifying changes in proteins and peptides that occur in various diseases or treatments. This goal cannot be accomplished with typical antibody based western blot, ELISA or even with currently available linear ion trap mass spectrometers due to lack of sensitivity, specificity, and/or high throughput of these approaches. Targeted peptide quantification is a highly selective and sensitive methodological approach for quantitative evaluation of dynamic changes of proteins and protein networks as well as the validation and utilization of biological markers. Towards this goal the PI and the users of the proposed instrument, have developed and established methodologies that employ stable isotope labeled peptides, proteomes and multiple reaction monitoring (MRM)/mass spectrometry (MS) workflows for the quantification of proteins in human samples and animal and cellular model systems. A TSQ Vantage unit (Thermo-Scientific) combined with an Eksigent Nano 2DLC, which has been operational in the TRL since September 2010, will remain until March 2013 on a lease supported by the University of Pennsylvania. We propose to acquire this remarkably productive unit. Chang-Gyu Hahn, M.D, Ph.D. as the P.I will assume overall responsibility for the equipment. Leadership will be equally divided between Chang-Gyu Hahn, M.D, Ph.D. and Ian Blair, Ph.D. Functioning as Co-P.I.'s. Dr. Hahn will focus on the operational aspects and Dr. Blair will provide scientific oversight.