HIGH RESOLUTION HYBRID FT-ICR MASS SPECT:ALZHEIMER, PARKINSON, HUNTINGTON, ALS

该子项目是利用由NIH/NCRR资助的共享仪器赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。列出的机构是用于资助的，不一定是研究者的机构。描述（由申请人提供）：需要一台高分辨率混合傅里叶变换离子回旋共振（FT-ICR）质谱仪，具有自上而下的蛋白质测序和自下而上的蛋白质组学快速占空比LC串联MS测量能力。该工具将成为支持超过11个NIH资助项目的具体目标的重要组成部分。这些项目涉及各种蛋白质结构/功能相关的研究，包括蛋白质-蛋白质和蛋白质-配体相互作用的测定，蛋白质磷酸化以及用于疾病检测和预后的蛋白质生物标志物的鉴定。该研究将影响一系列人类健康问题，包括神经退行性疾病，如亨廷顿病、阿尔茨海默病、帕金森病和肌萎缩侧索硬化症（ALS）、呼吸系统疾病、心血管和炎症性疾病以及癌症。对于完整肽/蛋白质和MS/MS实验产生的产物离子，混合FT-ICR质谱仪的质量测量精度将低于百万分之二。它将包括用于增加动态范围的存储捕获装置，并具有快速数据依赖LC-MS/MS的能力，以及足以测量大的完整蛋白质的同位素分布的分辨率，以提高质量准确度。该系统的独特之处将是电子捕获解离（ECD）和红外多光子解离（IRMPD）的能力，离子活化方法有利于自上而下的蛋白质测序和翻译后修饰的鉴定/定位。ECD大大提高了解离完整蛋白质以获得完整序列信息的能力，并有望检测翻译后修饰。具有这些独特功能的仪器目前在加州大学洛杉矶分校还没有。该仪器将是一个核心，将由加州大学洛杉矶分校新成立的分子仪器中心支持和管理，它将为整个机构的研究人员提供服务。

This subproject is one of many research subprojects utilizing the resources provided by a Shared Instrumentation Grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the grant, which is not necessarily the institution for the investigator. DESCRIPTION (PROVIDED BY APPLICANT): A high-resolution hybrid Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer with capabilities for top-down protein sequencing and rapid duty-cycle LC-tandem MS measurements for bottom- up proteomics is requested. This instrument will be a vital component to support the specific aims of over 11 NIH-funded projects. The projects involve a variety of protein structure/function-related research, including the determination of protein-protein and protein-ligand interactions, protein phosphorylation, and the identification of protein biomarkers for disease detection and prognosis. The research will impact a range of human health issues, including neurodegenerative diseases, such as Huntington's disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), respiratory illnesses, cardiovascular and inflammatory diseases, and cancer. The hybrid FT-ICR mass spectrometer will be capable of sub-2 parts-per-million mass measurement accuracy for both intact peptides/proteins and product ions derived from MS/MS experiments. It will include a storage trapping device for increased dynamic range and have capabilities for rapid data dependent LC-MS/MS, and a resolving power sufficient to measure the isotope distribution of large, intact proteins for improved mass accuracy. Unique to this system will be capabilities for electron capture dissociation (ECD) and infrared multiphoton dissociation (IRMPD), ion activation methods advantageous for top-down protein sequencing and identification/localization of post-translational modifications. ECD greatly improves the ability to dissociate intact proteins to derive complete sequence information, as well as holding the promise of detection of post-translational modifications. An instrument with these unique capabilities is not available currently at UCLA. The instrument will be a centerpiece and will be supported and administered by the newly-created Molecular Instrumentation Center at UCLA, and it will serve researchers from across the institution.