Thermoscientific TSQ Vantage Mass Spectrometer

描述（由申请人提供）：本提案要求资金购买三重四极质谱仪，以支持由Fred哈钦森癌症研究中心（FHCRC）的9名主要研究者以及来自华盛顿大学和儿童医院的癌症联盟成员领导的12个NIH资助项目。将受益于这种仪器的项目跨越了癌症研究的各个重要领域。具体而言，该仪器将用于了解丝氨酸/苏氨酸磷酸化事件在细胞间通讯中的作用;确定Src激酶调节信号通路中酪氨酸磷酸化事件的重要性;测量蛋白质泛素化通路和蛋白质质量控制之间的关系;验证乳腺癌、胰腺癌、前列腺癌、卵巢癌和肺癌中的血清生物标志物;并测量肿瘤“绘画”试剂的血清半衰期。该中心目前的质谱仪器（离子阱和离子阱/混合仪器）主要用于大型蛋白质组分析（例如，发现）研究，但不太适合需要靶向特定分子的实验工作流程的应用。具体而言，这些项目需要一种仪器，该仪器能够执行1）使用前体离子扫描的特定蛋白质修饰的定性测定和2）使用单/多反应监测（S/MRM）的血清中大量（100 s至1000 s）肽的高灵敏度多重定量测定。三重四极质谱仪是唯一适合满足这些要求。目前NIH资助的具有这些要求的研究将需要每年在该仪器上进行超过2416次注射，或超过87%的利用率。如果授予，三重四极杆仪器将由FHCRC蛋白质组学共享资源操作，其中存在操作，维护和管理仪器的专业知识，并且存在政策以确保整个FHCRC和联盟社区以及该地区其他NIH资助的研究人员都可以使用。此外，FHCRC支持计算蛋白质组学共享资源，由拥有专业知识和经验的中心教师管理，以支持利用仪器生成的数据所需的计算基础设施。所要求的工具将满足用户社区的当前和未来需求，并支持NIH资助的FHCRC研究。 公共卫生相关性：通过质谱法进行蛋白质分析是尖端生物医学研究中最强大和最具扩展性的分析工具之一，获得蛋白质组学技术对于充分了解人类疾病的生物学基础以及发现和验证蛋白质生物标志物以更好地诊断疾病和监测治疗效果至关重要。本申请中要求的三重四极质谱仪将为Fred哈钦森癌症研究中心的NIH资助的研究人员提供至关重要的蛋白质组学数据，用于1）通过生物标志物验证早期检测卵巢癌、肺癌、胰腺癌、前列腺癌和乳腺癌，2）开发检测癌症成像剂的灵敏测定法，和3）与信号转导途径、染色质生物学、蛋白质质量控制和细胞-细胞通讯相关的蛋白质修饰的灵敏检测。最终，该仪器产生的数据将有助于在分子水平上更好地了解癌症，并改善癌症患者的检测和结果。

DESCRIPTION (provided by applicant): This proposal requests funds to purchase a triple quadrupole mass spectrometer to support than 12 NIH-funded projects led by 9 principal investigators at the Fred Hutchinson Cancer Research Center (FHCRC) as well as Cancer Consortium members from the University of Washington and Children's Hospital. Projects that will benefit from this instrumentation span a variety of areas important for cancer research. Specifically the instrument will be used to understand the role of serine/threonine phosphorylation events in cell-cell communication; determine the importance of tyrosine phosphorylation events in Src kinase-modulated signaling pathways; measure the relationship between protein ubiquitination pathways and protein quality control; validate serum biomarkers in cancers of the breast, pancreas, prostate, ovary, and lung; and measure the serum half life of tumor "painting" reagents. Current mass spectrometry instrumentation at the Center (ion- trap and ion-trap/hybrid instruments) is used primarily for large proteomic profiling (e.g., discovery) studies, but is not well suited for applications that require experimental workflows that target specific molecules. Specifically, these projects require an instrument capable of performing 1) qualitative assays of specific protein modifications using precursor ion scanning and 2) highly-sensitive multiplexed quantitative assays for large numbers (100s to 1000s) of peptides in serum using Single/Multiple Reaction Monitoring (S/MRM). The triple quadrupole mass spectrometer is uniquely suited to meet these requirements. Current NIH-funded research with these requirements will demand over 2416 injections onto this instrument per year, or over 87% utilization. If awarded, the triple quadrupole instrument would be operated by the FHCRC Proteomics Shared Resource, where expertise exists to operate, maintain, and manage the instrument, and policies exist to ensure it is accessible to the entire FHCRC and Consortium community, as well as other NIH-funded investigators in the region. Moreover, the FHCRC supports a Computational Proteomics Shared Resource, managed by Center faculty who have expertise and experience to support the computational infrastructure needed to make use of the data generated by the instrument. The requested instrument will address both immediate and future needs of the user community and support NIH-funded research at the FHCRC. PUBLIC HEALTH RELEVANCE: Protein analysis by mass spectrometry is one of the most powerful and expanding analytical tools in cutting-edge biomedical research, and access to proteomics technology is critical to fully understand the biological basis of human disease and to discover and validate protein biomarkers to better diagnose disease and monitor treatment efficacy. The triple quadrupole mass spectrometer requested in this application will provide NIH funded researchers at the Fred Hutchinson Cancer Research Center critically important proteomics data for 1) the early detection of ovarian, lung, pancreatic, prostate and breast cancer through biomarker validation, 2) the development of sensitive assays to detect cancer imaging agents, and 3) the sensitive detection of protein modifications associated with signal transduction pathways, chromatin biology, protein quality control, and cell-cell communication. Ultimately, data produced from this instrument will lead to a better understanding of cancer at the molecular level and improved detection and outcomes for people afflicted with cancer.