HIGH RESOLUTION HYBRID FT-ICR MASS SPECT: CANCER, PROSTATE CANCER

这个子项目是利用由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。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是用于拨款的，而不一定是用于调查人员的机构。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，具有自上而下蛋白质测序和自下而上蛋白质组学的快速占空比LC-Tandem MS测量能力。该文书将是支持美国国立卫生研究院资助的11个项目的具体目标的重要组成部分。这些项目涉及各种与蛋白质结构/功能相关的研究，包括确定蛋白质-蛋白质和蛋白质-配体相互作用，蛋白质磷酸化，以及识别用于疾病检测和预后的蛋白质生物标记物。这项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，呼吸系统疾病，心血管和炎症性疾病，以及癌症。混合FT-ICR质谱仪将能够对完整的多肽/蛋白质和MS/MS实验的产品离子进行低于百万分之2的质量测量精度。它将包括一个存储捕获装置，用于增加动态范围，并具有依赖于数据的快速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，以提高质量准确性。该系统的独有功能是电子捕获解离(ECD)和红外多光子解离(IRMPD)，这是一种离子激活方法，有利于自上而下的蛋白质测序和翻译后修饰的识别/定位。ECD极大地提高了解离完整蛋白质以获得完整序列信息的能力，以及检测翻译后修饰的前景。加州大学洛杉矶分校目前还没有具备这些独特功能的仪器。该仪器将是核心，将由加州大学洛杉矶分校新成立的分子仪器中心提供支持和管理，并将为来自该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.