Ultra-High Resolution Mass Spectrometer for Biomedical Research

描述（由申请人提供）：要求高磁场，超高分辨率傅里叶变换离子回旋共振（FT-ICR）质谱仪，具有增强自上而下蛋白质测序和代谢物检测的能力。该仪器将是支持超过11个nih资助项目研究目标的重要组成部分。这些研究涉及多种蛋白质结构相关的研究，包括蛋白质-蛋白质和蛋白质-配体相互作用、蛋白质磷酸化、膜蛋白结构的测定，以及用于疾病检测和预后的蛋白质生物标志物的鉴定。这项研究将影响一系列人类健康问题，包括衰老、神经退行性疾病，如亨廷顿氏病、阿尔茨海默病、帕金森病、肌萎缩侧索硬化症（ALS）和癌症。超高分辨率FT-ICR质谱仪将能够对来自串联质谱（MS/MS）实验的完整肽/蛋白质和产物离子进行百万分之一到十亿分之一的质量测量精度，以及小分子代谢物鉴定。它将具有在ICR捕获/检测设备中进行多级MS-n实验（n大于2）的能力，从而允许使用红外多光子解离（IRMPD）和电子捕获解离（ECD）进行高级自上而下的分析，以实现ICR细胞中的有效离子激活和解离。电子转移离解（ETD）将作为一种可选的离解方法。ETD和ECD都极大地提高了分离完整蛋白以获得完整序列信息的能力，并有望直接检测翻译后修饰。该仪器将成为加州大学洛杉矶分校分子仪器中心的核心设备，并将由该中心提供支持和管理，它将为该机构和附近机构的研究人员提供服务。

DESCRIPTION (provided by applicant): A high-magnetic field, ultra-high resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer with capabilities for enhanced top-down protein sequencing and metabolite detection is requested. This instrument will be a vital component to support the research aims of over 11 NIH-funded projects. The studies involve a variety of protein structure-related research, including the determination of protein-protein and protein-ligand interactions, protein phosphorylation, membrane protein structure, and the identification of protein biomarkers for disease detection and prognosis. The research will impact a range of human health issues, including aging, neurodegenerative diseases, such as Huntington's disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), and cancer. The ultra-high resolution FT-ICR mass spectrometer will be capable of sub-parts-per-million to parts-per-billion mass measurement accuracy for intact peptides/proteins and product ions derived from tandem mass spectrometry (MS/MS) experiments, and small molecule metabolite identification. It will have capabilities for multistage MS-n experiments (n greater than 2) to be conducted in the ICR trapping/detection device, thus permitting advanced top-down analysis using infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) for efficient ion activation and dissociation in the ICR cell. Electron transfer dissociation (ETD) will be available as an alternative dissociation method. Both ETD and ECD greatly improve the ability to dissociate intact proteins to derive complete sequence information, as well as holding the promise of direct detection of post-translational modifications. The instrument will be a centerpiece and will be supported and administered by the Molecular Instrumentation Center at UCLA, and it will serve researchers from across the institution and nearby institutions. PUBLIC HEALTH RELEVANCE: The new instrumentation will benefit a wide range of biomedical studies. The high sensitivity and high resolution capabilities of the system will provide a new means to identify the mechanistic basis of a number of human diseases, such as neurodegenerative disorders, and it may be used to identify new protein markers of cancer. The availability of this new, state-of-the-art mass spectrometer will require highly trained scientists to be hired and maintained for its operational use.