Acquisition of OrbiTrap Eclipse w/FAIMS mass spectrometer

收购 OrbiTrap Eclipse 和 FAIMS 质谱仪

• 批准号: 10412531
• 负责人: Philip R Gafken
• 金额: $ 110.06万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10412531
• 关键词: 9 year old; Acute Myelocytic Leukemia; African American; Child; Chromosome Segregation; Complex; Databases; Dysmyelopoietic Syndromes; Ensure; Fred Hutchinson Cancer Research Center; Funding; Goals; Grant; Hematopoietic Stem Cell Transplantation; Human papilloma virus infection; Immune response; Institution; Investigation; Ions; Maintenance; Major Histocompatibility Complex; Malignant Neoplasms; Malignant neoplasm of ovary; Mass Spectrum Analysis; Molecular; Mutation; Outcome; Pathway interactions; Patients; Peptides; Phenotype; Post-Translational Protein Processing; Proteins; Proteomics; RNA; Request for Applications; Research; Research Institute; Research Personnel; Research Support; Rod; Running; Sampling; Scanning; Services; Speed; Spliceosomes; Streptococcal Infections; Streptococcus Group B; System; Time; United States National Institutes of Health; Universities; Virulence Factors; Wait Time; Washington; base; cancer care; chimeric antigen receptor; design; energy balance; experience; experimental study; instrument; instrumentation; ion mobility; leukemia; malignant breast neoplasm; mass spectrometer; novel; operation; peptide I; protein biomarkers; side effect; targeted treatment; transmission process

Project Summary/Abstract: This application is for funds to purchase a Thermo Scientific Orbitrap Eclipse w/FAIMS mass spectrometry system for Fred Hutchinson Cancer Research Center’s Proteomics Facility. The facility supports the Fred Hutchinson/University of Washington Cancer Consortium which is made up of these two institutions and research partners at Seattle Children’s Research Institute and the Seattle Cancer Care Alliance and has a combined annual NIH grant base exceeding $300 million. Our facility has been operating for 20 years and we have a combined 75+ years’ experience in the operation, maintenance, and management of mass spectrometry instrumentation, and in the design and analysis of proteomics experiments. Current discovery-based mass spectrometry instrumentation in the facility is running at capacity causing long wait-times for service. Additionally, outdated instrumentation in the facility it being used for multiplexed proteomics and high-sensitivity experiments, but that instrumentation lacks the sensitivity and quality needed to properly support those experiments. In this application we are requesting the Orbitrap Eclipse w/FAIMS to replace a 9-year old Orbitrap Elite in order to achieve two goals: the first is to increase sample capacity/throughput of our facility to reduce wait-times and the second is to replace the outdated instrumentation to ensure discovery-based proteomics research is carried out on technically appropriate instrumentation. With TMT-based discovery experiments and analysis of major histocompatibility complex I (MHC-I) peptides being the most frequent requests for proteomics services, the Orbitrap Eclipse w/FAIMS is the most suitable instrument based on the instrument’s 1) scan speeds up to 40 Hz in the Orbitrap and 45 Hz in the ion trap for thorough sampling of complex peptide mixtures, 2) high ion transmission and ion mobility separations for high sensitivity, 3) real-time database searching for accurate multiplexed quantification, 4) new segmented quadrupole with hyperbolic rods for more accurate TMT quantification, and 5) novel active beam guide for enhanced sensitivity and robustness. This state-of-the art instrument would immediately support the research of 11 investigators funded by 14 NIH grants that include investigations identifying the proteins and protein modifications that regulate chromosome segregation, defining molecular pathways associated with energy balance, determining how mutations in RNA spliceosome proteins alter cellular phenotypes, understanding virulence factors associated with Group B streptococcus infection, identifying proteins that influence chimeric antigen receptor’s efficacy and side effects, and discovering protein biomarkers in ovarian cancer, breast cancer, and acute myeloid leukemia. Other projects aim to rapidly identify major MHC- I peptides to better understand immune system response, develop targeted therapies against myelodysplasia, leukemias, and other cancers driven by human papilloma virus infection, and better understand hematopoietic stem cell transplant outcomes in African American patients.

项目摘要/摘要： 该应用程序是为了购买带有质谱的Thermo Scientific Orbitrap Eclipse 弗雷德·哈钦森癌症研究中心的蛋白质组学设施的系统。该设施支持弗雷德 哈钦森/华盛顿大学癌症联盟由这两个机构和研究组成 西雅图儿童研究所和西雅图癌症护理联盟的合作伙伴，合计 年度NIH赠款基地超过3亿美元。我们的设施已经运营了20年，我们有一个 质谱法的运营，维护和管理中共有75年以上的经验 仪器，以及蛋白质组学实验的设计和分析。当前基于发现的质量 设施中的光谱仪器正在运行，导致长时间的服务。此外， 设施中过时的仪器用于多路复用蛋白质组学和高敏性实验， 但是该仪器缺乏适当支持这些实验所需的敏感性和质量。在这个 申请我们要求使用faims的Orbitrap Eclipse替换9岁的Orbitrap Elite，以便为了 实现两个目标：第一个目标是提高我们设施的样本容量/吞吐量，以减少等待时间和 第二是替换过时的仪器，以确保进行基于发现的蛋白质组学研究 在技​​术上适当的仪器上。通过基于TMT的发现实验和主要的分析 组织相容性综合体I（MHC-I）Pepperides是最频繁的蛋白质组学服务请求， 带有FAIMS的Orbitrap Eclipse是基​​于乐器的最合适的仪器1）扫描速度高达40 Hz 在Orbitrap和45 Hz中，在离子陷阱中以彻底取样复杂的肽混合物，2）高离子 高灵敏度的传输和离子移动性分离，3）实时数据库搜索准确的 多路复用定量​​，4）用双曲线杆进行新的分段四极杆，以获得更精确的TMT 定量和5）新型的主动梁指南，以增强灵敏度和鲁棒性。这是最先进的 工具将立即支持由14个NIH赠款资助的11位调查人员的研究，包括 调查鉴定调节染色体分离的蛋白质和蛋白质修饰，定义 与能量平衡相关的分子途径，确定RNA剪接体蛋白中的突变如何 改变细胞表型，了解与B组链球菌感染相关的病毒因子， 鉴定影响嵌合抗原受体的有效性和副作用的蛋白质，并发现蛋白质 卵巢癌，乳腺癌和急性髓样白血病的生物标志物。其他项目旨在快速识别 主要MHC- I肽可以更好地了解免疫系统反应，开发了针对的靶向疗法 由人类乳头状瘤病毒感染驱动的骨髓增生，白血病和其他癌症，并更好地理解 非裔美国人患者的造血干细胞移植结局。