MALDI-TOF Mass Spectrometer

该提案请求支持购买一台基质辅助激光解吸电离飞行时间质谱仪(MALDI-TOF MS)，用于儿童医院奥克兰研究所(CHORI)，以促进一系列涉及单核苷酸多态(SNP)和蛋白质组分析的项目。我们强调MALDI-TOF MS方法与其他技术相比的适当性，这一补充对加强我们的研究工作的价值，以及将这一技术应用于拟议的研究应用的及时性。MALDI-TOF MS提供了一种高效的方法来识别SNPs，SNPs是人类群体中最常见的DNA序列变异类型，使用高通量的多重技术群体。多重分析，允许在多个位点同时对单个样本进行基因分型，并需要一个易于适应不断变化的研究需求的系统。尽管存在基于SNP的多重基因分型的替代方法，但大多数方法都非常耗时且灵活性较差。利用MALDI-TOF MS提供的多重SNP分析技术，可以高效、准确、特定和可靠地对大量样本进行分型。购买这种仪器将使CHORI的一个用户财团受益，他们正在寻找调节疾病易感性、严重性和对环境毒素的敏感性的基因。正在研究的疾病包括镰状细胞性贫血、地中海贫血、营养不良、结核病、糖尿病、哮喘、出生缺陷、性传播疾病和沙眼。在更广泛的背景下，在CHORI获得MALDI-TOF MS将促进关于遗传变异在人类健康中的作用的知识的应用。蛋白质组学是对蛋白质的大规模分析，它通过关注负责调节细胞功能的基因产物来补充基因组学。蛋白质组学侧重于蛋白质分析的几个方面：识别蛋白质及其翻译后修饰，用于比较健康和疾病状态下蛋白质表达的差异显示，以及阐明结构和功能所需的蛋白质-蛋白质相互作用的研究。MALDI-TOF MS是一种成熟和强大的MS，它实现了上述所有蛋白质组功能。具有执行这些任务能力的MALDI-TOF MS仪器的可用性，以及使用同位素编码亲和标签(ICAT)的定量分析，将极大地增强我们同时表征可能涉及线粒体功能的多个蛋白质以及与健康和疾病相关的其他生理状态的能力。

The proposal requests support to purchase a Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometer (MALDI-TOF MS) for use at Children's Hospital Oakland Research Institute (CHORI) to facilitate an array of projects involving single nucleotide polymorphism (SNP) and proteome analysis. We emphasize the appropriateness of the MALDI-TOF MS approach compared to other technologies, the value of this addition to enhancing our research efforts, and the timeliness in the adoption of this technology to the proposed research applications. MALDI-TOF MS offers an efficient means of identifying SNPs, the most common type of DNA sequence variations in human populations, using high throughput multiplex technology populations. Multiplex analysis, allows simultaneous genotyping of a single sample at multi loci, and requires a system that is easily adaptable to the changing needs of research. Although alternative approaches to multiplex SNP-based genotyping exist, most of these are considerably more time consuming and less flexible. Use the multiplex SNP analysis technique afforded by MALDI-TOF MS, large panels of samples can be typed efficiently, accurately, specifically, and reliably. Acquisition of this instrument will benefit a consortium of users at CHORI who are engaged in a search for genes that modulate disease susceptibility and severity and sensitivity to environmental toxins. Among the diseases under study are sickle cell anemia, thalassemia, nutritional deficiencies, tuberculosis, diabetes, asthma, birth defects, sexually transmitted disease, and trachoma. In a broader context access to MALDI-TOF MS at CHORI will facilitate the application of knowledge regarding the role of genetic variations in human health. Proteomics, the large scale analysis of proteins, complements genomics by focusing on the gene products responsible for mediating cellular function. Proteomics focuses on several aspects of protein analysis: the identification of proteins and their post-translational modifications, the "differential display" utilized in comparing protein expression in health and disease states, and the studies of protein-protein interactions required to elucidate structure and function. MALDI-TOF MS is a well- established and robust which fulfills all of the proteomic functions described above. The availability of a MALDI-TOF MS instrument with the capabilities to perform these tasks, as well as quantitative analysis using isotope coded affinity tags (ICAT), will greatly enhance our ability to simultaneously characterize multiple proteins potentially involved mitochondrial function and other physiological states involved in health and disease.