5500 QTRAP

描述(由申请人提供)：我们建议获得一台应用生物系统SCHEX QTRAP 5500混合式三重四极-线性离子陷阱质谱仪(MS)，用于对生物医学上重要的复杂脂质进行LC/MS/MS分析。该程序将受益于这种当代仪器的灵敏度和多功能性，它可以作为三重四极杆操作，能够执行串联扫描模式，这些模式已被证明在我们对生物样本中的脂质的分析中具有无价的价值。我们现有的三重四极杆质谱仪是一种较老的仪器，维护起来越来越困难，而且缺乏当代仪器的灵敏度。所要求的仪器的第三个四极杆也可以作为线性离子陷阱(LIT)操作，允许将其用于串联四极杆照明配置，从而允许进行用于脂质结构测定的极高灵敏度的MSN实验。申请的仪器将放置在华盛顿大学(Wu)医学部MS设施的1号站点，这是NCRR支持的Wu生物医学MS资源(P41-RR00954)的一个站点，也是NIDDK支持的Wu糖尿病研究和培训中心(DRTC，P60-DK20579)和Wu临床营养研究单元(CNRU，P30-DK56341)的核心MS实验室。因此，这个设施为这里和其他地方的NIH资助的调查人员提供了广泛的服务。该仪器将配备一个与纳米高效液相连接的纳米放射源，该系统将提供一个平台，用于分离和分析与糖尿病及其并发症、艾滋病毒/艾滋病等代谢性疾病的发病机制有关的复杂脂分子，进行神经生理学研究，并表征控制其毒力的病原微生物细胞膜的成分。一个明确的目标是促进NIH资助的研究我们MS设备的许多用户的生物医学重要脂质的研究，该应用中的八个主要项目被描述为例子：(1)磷脂衍生的介体和胰岛素分泌、葡萄糖耐量和动脉粥样硬化(John Turk，Wu)；(2)磷脂水解和内质网应激诱导的胰岛？-细胞凋亡(Sasanka Ramanadham博士，Wu)；(3)使用果蝇来确定葡萄糖毒性的候选修饰物(Thomas Baranski，Wu)；(4)糖结合物和鞘脂在动质寄生虫生长和毒力中的作用(Steven Beverley，Wu博士和James Bangs博士，Uni.(5)致病沙门氏菌耐药和毒力的分子基础(Eduardo Groisman博士、Wu博士和石益新博士，Univ.研究主题包括：(1)人类免疫缺陷和免疫缺陷(亚利桑那州-坦佩)；(6)结核分枝杆菌细胞壁脂分子种类和破坏性宿主组织反应的细胞机制(康奈尔大学大卫·拉塞尔博士)；(7)嗅觉模式识别的神经机制(蒂莫西·圣博士，吴)；和(8)艾滋病毒感染与脂质生物化学(凯文·雅拉什斯基博士和大卫·克利福德博士，吴)。 公共卫生相关性：所要求的应用生物科学SCHEX QTRAP 5500质谱仪将用于对生物材料进行测量，以提供与糖尿病、心血管疾病、传染病、脑功能和艾滋病相关的几个重要生物医学问题的信息。这些包括调节胰岛素分泌的β细胞的功能和生存的机制，控制它们感染和杀死人类能力的致病微生物的细胞表面的特性，以及为什么艾滋病患者过早地患上心脏和血管疾病。这些信息将为开发诊断和治疗人类疾病的新方法提供洞察力，从而改善人类健康。

DESCRIPTION (provided by applicant): We propose to acquire an Applied Biosystems Sciex QTRAP 5500 hybrid triple quadrupole-linear ion trap mass spectrometer (MS) for LC/MS/MS analyses of biomedically important complex lipids. This program will benefit from the sensitivity and versatility of this contemporary instrument, which can be operated as a triple quadrupole capable of performing tandem scanning modes that have proven invaluable in our analyses of lipids in biological specimens. Our existing triple quadrupole MS is an older instrument that is becoming difficult to maintain and lacks the sensitivity of contemporary instruments. The third quadrupole of the requested instrument can also be operated as a linear ion trap (LIT), permitting its use in a tandem quadrupole-LIT configuration that permits extremely high sensitivity MSn experiments for lipid structural determinations. The requested instrument is to be placed in Site 1 of the Washington University (WU) Medicine Department MS Facility, which is one site of the NCRR-supported WU Biomedical MS Resource (P41-RR00954) and also serves as a core MS laboratory for the WU Diabetes Research and Training Center (DRTC, P60-DK20579) and the WU Clinical Nutrition Research Unit (CNRU, P30-DK56341) that are supported by NIDDK. This facility thus serves a wide range of NIH-funded investigators here and elsewhere. The instrument will be equipped with a nanospray source interfaced with a nano-HPLC, and this system will provide a platform for separation and analysis of complex lipid molecules relevant to the pathogenesis of metabolic diseases such as diabetes mellitus and its complications, to HIV/AIDS, to neurophysiologic research, and to characterizing components of cell envelopes of pathogenic microorganisms that govern their virulence. A specific aim is to further the NIH-funded research of the many users of our MS facility who study biomedically important lipids, and eight major projects are described in this application as examples: (1) Phospholipid-derived mediators and insulin secretion, glucose tolerance, and atherogenesis (Dr. John Turk, WU); (2) Phospholipid hydrolysis and ER stress-induced apoptosis of pancreatic islet ?-cells (Dr. Sasanka Ramanadham, WU); (3) Using Drosophila to identify candidate modifiers of glucose toxicity (Dr. Thomas Baranski, WU); (4) Role of glycoconjugates and sphingolipids in kinetoplastid parasite growth and virulence (Dr. Steven Beverley, WU, and Dr. James Bangs, Univ. Wisconsin-Madison); (5) Molecular bases of antimicrobial resistance and virulence in pathogenic Salmonella gram-negative bacteria (Dr. Eduardo Groisman, WU, and Dr. Yixin Shi, Univ. Arizona-Tempe); (6) Mycobacterium tuberculosis cell wall lipid molecular species and cellular mechanisms of destructive host tissue reactions in a murine granuloma model (Dr. David Russell, Cornell Univ.); (7) Neural mechanisms of olfactory pattern recognition (Dr. Timothy Holy, WU); and (8) HIV-infection and lipid biochemistry (Dr. Kevin Yarasheski and Dr. David Clifford, WU). PUBLIC HEALTH RELEVANCE: The requested Applied Biosciences Sciex QTRAP 5500 mass spectrometer will be used to perform measurements on biological materials that will provide information on several important biomedical problems that are relevant to diabetes, cardiovascular disease, infectious disease, brain function, and AIDS. These include mechanisms regulating the function and survival of insulin-secreting beta cells, properties of the cell surfaces of pathogenic microorganisms that govern their ability to infect and kill humans, and why patients with AIDS develop diseases of the heart and blood vessels prematurely. Such information will provide insight into developing new ways to diagnose and treat human diseases and thereby improve human health.