Fusion Lumos Orbitrap System for Quantitative Proteomics and Metabolomics Applications

用于定量蛋白质组学和代谢组学应用的 Fusion Lumos Orbitrap 系统

• 批准号: 10175908
• 负责人: Nichole A Reisdorph
• 金额: $ 127.25万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2022-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10175908
• 关键词: Acetylation; Alzheimer' s Disease; Biomedical Research; Colorado; Diabetes Mellitus; Disease; Dissociation; Drug Delivery Systems; Electron Transport; Equipment; Faculty; Funding; Health; Human; Hybrids; Immunologics; Liquid Chromatography; Mass Spectrum Analysis; Medical; Metabolic syndrome; Methods; Molecular Structure; Oxidation-Reduction; Peptides; Pharmacologic Substance; Pharmacy Schools; Post Translational Modification Analysis; Post-Translational Protein Processing; Proteome; Proteomics; Publishing; Regulation; Research; Research Personnel; Research Project Grants; Resolution; Science; Services; System; Technology; United States National Institutes of Health; Universities; base; direct application; experimental study; extracellular vesicles; improved; instrument; instrumentation; insulin sensitivity; lipidome; mass spectrometer; mass spectrometry shared resource; mast cell; metabolome; metabolomics; programs; small molecule; success

Project Summary This application is for an Orbitrap Lumos Fusion liquid chromatography mass spectrometer system to be housed within the Mass Spectrometry Facility at the Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) at University of Colorado, Anschutz Medical Campus. This instrument will be used to advance several translational projects that focus on quantitative and discovery-based proteomics and the analysis of post- translational modifications (PTMs), such as acetylation, with direct application to human health and disease. The instrument will also be used for metabolomics projects that require high resolving power to improve identification of unknown compounds. The Users’ projects are currently being conducted on older, Q-TOF instrumentation that cannot acquire the depth of proteome coverage or resolution required for multiplex proteomics experiments, PTM analysis, or fine molecular structure elucidation. Hence there is an urgent need for this instrumentation. The Orbitrap Lumos has several critical features for the intended applications including exceptional sensitivity, ultra high resolving power, MSn capabilities, electron transfer dissociation (ETD), versatility in quantitative capabilities, and well-published methods. Dr. David Ross will utilize the Orbitrap Lumos to reveal mechanisms underlying insulin sensitivity through in-depth, quantitative proteomics and PTM analysis using ETD, with the potential to impact therapies directed at metabolic syndrome. Dr. Thomas Delong will employ ETD for de novo hybrid peptide discovery to examine immunological origins of certain diseases, such as diabetes and Alzheimer’s disease. Dr. Anchordoquy will require the instrument to achieve deep proteome, metabolome, and lipidome coverage of extracellular vesicles towards improved drug delivery systems. Dr. Brown requires a highly sensitive and specific redox proteomics approach to understanding regulation of mast cell activation. Finally, the instrument will be used by Dr. Reisdorph and others to support the identification of small molecules using its capabilities in multi-stage experiments, MSn, high resolution, and accurate mass. Our long-term objective is to utilize the Orbitrap Lumos to further develop our programs in acetylomics, PTM quantitation, and metabolomics. As our Core currently lacks any type of Orbitrap technology, our proteomics and metabolomics services have hit a plateau; cutting edge instrumentation is required to take the research of our faculty to the next level. The SSPPS has committed over $500,000 (not including equipment) in the past 5 years towards the improvements of mass spectrometry facility, which has been supported by SSPPS for almost 20 years. Our objective is to continue to provide our investigators with a shared mass spectrometry resource to support current and proposed NIH-funded biomedical research. This Orbitrap is vital to the continued functioning of the facility as a cutting- edge enterprise and for the success of several potentially high impact research projects.

项目摘要 该应用程序用于安装Orbitrap Lumos Fusion液相色谱质谱仪系统 在斯卡格斯药学和制药科学学院（SSPPS）的质谱设施内 在科罗拉多大学安舒茨医学院。该工具将用于推进几个 翻译项目，重点是定量和发现为基础的蛋白质组学和分析后， 翻译修饰（PTM），如乙酰化，直接应用于人类健康和疾病。的 仪器也将用于代谢组学项目，这些项目需要高分辨率来提高识别能力 未知的化合物。用户项目目前正在较旧的Q-TOF仪器上进行 不能获得多重蛋白质组学实验所需的蛋白质组覆盖深度或分辨率， PTM分析或精细分子结构解析。因此，迫切需要这种仪器。 Orbitrap Lumos具有几个用于预期应用的关键特性，包括出色的灵敏度， 超高分辨率，MSn能力，电子转移解离（ETD），定量分析的多功能性 能力，以及公开的方法。大卫罗斯博士将利用轨道探测器Lumos来揭示 通过使用ETD进行深入的定量蛋白质组学和PTM分析， 可能影响针对代谢综合征的治疗。托马斯德龙博士将聘请ETD进行重新治疗 杂交肽发现，以检查某些疾病的免疫起源，如糖尿病和阿尔茨海默氏症 疾病Anchordoquy博士将需要该仪器来实现深层蛋白质组、代谢组和脂质组 细胞外囊泡的覆盖，以改善药物递送系统。布朗博士需要一个高度敏感的 和特定的氧化还原蛋白质组学方法来理解肥大细胞活化的调节。最后 Reisdorph博士和其他人将使用该仪器来支持使用其 多阶段实验、MSn、高分辨率和精确质量的能力。我们长远的目标是 利用Orbitrap Lumos进一步发展我们在乙酰组学、PTM定量和代谢组学方面的项目。 由于我们的核心目前缺乏任何类型的Orbitrap技术，我们的蛋白质组学和代谢组学服务已经达到 一个高原;尖端仪器需要采取我们的教师的研究到一个新的水平。的 在过去5年，SSPPS已承诺超过50万美元（不包括设备）用于改善 质谱仪设施，这已支持了近20年的SSPPS。我们的目标是 继续为我们的研究人员提供共享的质谱资源，以支持当前和拟议的 NIH资助的生物医学研究。这个轨道阱对该设施的持续运作至关重要，因为它是一个切割- 边缘企业和几个潜在的高影响力的研究项目的成功。