Orbitrap XL/ETD Mass Spectrometer

描述(由申请者提供)：申请资金购买Thermo Fisher LTQ Orbitrap XL质谱仪、微型高效液相色谱系统和计算机集群硬件，用于德克萨斯大学圣安东尼奥分校健康科学中心的机构质谱学实验室，在苏珊·温特劳布博士的指导下，苏珊·温特劳布博士在生物医学质谱仪方面拥有30多年的经验。目前，对2005年10月安装的大量使用的Thermo Fisher LTQ进行了毛细管HPLC-ESIMS/MS分析。圣安东尼奥没有高分辨率/高质量精度的质谱仪。所要求的仪器的主要用途将是评估蛋白质数量的相对差异和确定蛋白质修饰的位置。给出了九个主要用户和两个未来用户的方案。主要使用者将研究的医学相关领域包括心血管疾病、糖尿病、酒精暴露和母婴营养；此外，还将研究各种关键的生化系统，如噬菌体组装、细胞接触介导的过程、单个TCA循环酶丢失造成的代谢缺陷、NADPH-细胞色素P450氧化还原酶、一氧化氮合酶和线粒体电子传输复合体的修饰。请求的Orbitrap XL将在许多方面增强用户组的项目。获得高质量精度的前体离子光谱将大大降低错误发现率，从而提高蛋白质鉴定的信心。高质量分辨率对于电荷状态的确定和对近等压物种的区分是必不可少的。多种片段策略(CAD、HCD和ETD)的使用将导致更成功地定位修饰位点，并为蛋白质鉴定/表征提供更大的序列覆盖率。最后，结合ETD进行自上而下分析的能力将有助于大肽和小蛋白的全面表征。除了建议的用户群体，Orbitrap的可用性将刺激其他研究人员在未来计划新的实验，这些实验可能会将他们的研究努力带入令人兴奋的新方向。因此，收购Orbitrap有可能对NIH资助的涵盖生物医学研究的所有学科的大量调查产生积极影响。公共卫生相关性收购所要求的Orbitrap XL质谱仪将推进圣安东尼奥德克萨斯大学健康科学中心六个不同系的九个主要用户的研究工作。主要使用者将研究的与医学相关的领域包括心血管疾病、糖尿病、酒精暴露和孕产妇/胎儿营养；此外，还将调查各种关键的生化系统。除了建议的用户群体，Orbitrap的可用性将刺激其他研究人员在未来计划新的实验，这些实验可能会将他们的生物医学研究努力带入令人兴奋的新方向。

DESCRIPTION (provided by applicant): Funds are requested to purchase a Thermo Fisher LTQ Orbitrap XL mass spectrometer, a micro HPLC system and computer cluster hardware for the Institutional Mass Spectrometry Laboratory of the University of Texas Health Science Center at San Antonio, under the direction of Dr. Susan Weintraub, who has over 30 years experience in biomedical mass spectrometry. At the present time, capillary HPLC-ESIMS/ MS analyses are conducted on a heavily-utilized Thermo Fisher LTQ that was installed in October 2005. There are no high resolution/high mass accuracy mass spectrometers in San Antonio. The major uses for the requested instrument will be for assessing relative differences in protein quantities and for identifying sites of protein modification. The projects of nine major users and two future users are presented. Medically-relevant areas that will be studied by the major users include cardiovascular disease, diabetes, ethanol exposure and maternal/fetal nutrition; in addition, a wide variety of key biochemical systems will be investigated, such as bacteriophage assembly, cell contact-mediated processes, metabolic defects due to loss of individual TCA cycle enzymes, NADPH-cytochrome P450 oxidoreductase, nitric oxide synthase and modification of mitochondrial electron transport complexes. The requested Orbitrap XL will enhance the projects of the user group in many ways. The acquisition of high mass accuracy precursor ion spectra will substantially lower false discovery rates, leading to higher confidence for protein identifications. High mass resolution will be essential for charge state determinations and for differentiating between nearly isobaric species. The availability of multiple fragmentation strategies (CAD, HCD and ETD) will result in more successful localization of sites of modification and greater sequence coverage for protein identification/characterization. Finally, the capability of top-down analysis in conjunction with ETD will facilitate comprehensive characterization of large peptides and small proteins. In addition to the proposed user group, availability of the Orbitrap will stimulate other investigators to plan new experiments in the future that may take their research endeavors into exciting new directions. Thus, acquisition of the Orbitrap has the potential to positively impact a large number of NIH-funded investigations covering the full array of disciplines in biomedical research. PUBLIC HEALTH RELEVANCE Acquisition of the requested Orbitrap XL mass spectrometer will advance the research efforts of nine major users in six different departments at the University of Texas Health Science Center at San Antonio. Medically-relevant areas that will be studied by the major users include cardiovascular disease, diabetes, ethanol exposure and maternal/fetal nutrition; in addition, a wide variety of key biochemical systems will be investigated. Beyond the proposed user group, availability of the Orbitrap will stimulate other investigators to plan new experiments in the future that may take their biomedical research endeavors into exciting new directions.