Thermo Fisher LTQ-Orbitrap XL Mass Spectrometer

描述(由申请人提供)：所附提案要求通过购买Thermo Fisher LTQ-Orbitrap质谱仪来扩大华盛顿大学的质谱学和蛋白质组学资源。这一仪器将对成功完成我们现有的NIH资助的项目起到无价的作用，该项目涉及蛋白质的定性和定量分析以及复杂混合物的蛋白质修饰。此外，我们的一些项目正在将定量蛋白质组学技术扩展到衡量周转率的变化。NIH及时完成这些研究项目的关键是质谱仪的可用性，该质谱仪能够：i)质量精度低于5ppm以区分相似质量的多肽；ii)单个光谱的动态范围&gt；1000；iii)依赖数据获得具有四极离子陷阱的灵敏度和速度的串联质谱图；以及iv)解析和检测复杂混合物中多电荷多肽的不寻常的同位素分布的能力。目前能够进行这些测量的质谱计已被超额认购，因此，几乎无法访问我们的授权用户组。我们建议通过收购共享混合质谱仪来解决这些限制，该混合质谱仪将线性四极离子陷阱的稳健性和速度与傅里叶变换质谱仪的分辨率、质量精度和动态范围相结合。所要求的仪器将使教员能够在全球范围内解决目前的技术限制，并改善样本分析瓶颈，这将提高华盛顿大学医学院现有和未来NIH资助项目的能力。 与公共卫生相关：我们正在请求支持购买一台质谱仪，用于对复杂蛋白质混合物进行定性和定量分析。这些分析将用于提高我们对基因组序列如何编码功能活的有机体的理解，识别新的生殖蛋白质，识别暴露在环境毒素中的生物标记物，理解导致双链DNA断裂的分子机制，涉及衰老的基本分子过程，等等。所有这些领域都提高了我们对人类疾病的理解、预防或治疗。

DESCRIPTION (provided by applicant): The enclosed proposal is requesting funds to expand the mass spectrometry and proteomics resources at the University of Washington through the purchase of a Thermo Fisher LTQ-Orbitrap mass spectrometer. This instrument will be invaluable in the successful completion of our existing NIH funded projects involving the qualitative and quantitative analysis of proteins and protein modifications of complex mixtures. Furthermore, a number of our projects are extending quantitative proteomics technology to the measurement of changes in the rate of turnover. Integral to the timely completion of these NIH research projects is the availability of a mass spectrometer capable of i) sub 5 ppm mass accuracy to distinguish between similar mass peptides, ii) a dynamic range of >1000 in a single spectrum, iii) data-dependent acquisition of tandem mass spectra with the sensitivity and speed of a quadrupole ion trap, and iv) the ability to resolve and detect unusual isotope distributions of multiply charged peptides within a complex mixture. Current mass spectrometers capable of these measurements are oversubscribed and, thus, can provide little to no access to our grants user groups. We propose to address these limitations through the acquisition of a shared hybrid mass spectrometer which combines the robustness and speed of a linear quadrupole ion-trap with the resolution, mass accuracy, and dynamic range of a Fourier transform mass spectrometer. The requested instrumentation will allow the faculty to address current technological limitations on a global level and improve the sample analysis bottleneck that will improve the capabilities of existing and future NIH funded projects within the University of Washington, College of Medicine. PUBLIC HEALTH RELEVANCE: We are requesting support to purchase a mass spectrometer for the qualitative and quantitative analysis of complex protein mixtures. These analyses will be used to improve our understanding of how a genome sequence encodes a functional living organism, to identify novel reproductive proteins, identify biomarkers of exposure to environmental toxins, understanding the molecular machinery responsible for double stranded DNA breaks, the basic molecular processes involved in aging, and more. All of these areas improve our understanding, prevention, or treatment of human disease.