5500 QTRAP

5500 量子陷阱

• 批准号: 7794730
• 负责人: JOHN W TURK
• 金额: $ 48.44万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-06 至 2011-05-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7794730
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Antimicrobial Resistance; Apoptosis; Arizona; Beta Cell; Biocompatible Materials; Biological; Blood Vessels; Brain; Cardiovascular Diseases; Cell Wall; Cell surface; Clinical Nutrition; Communicable Diseases; Complex; Diabetes Mellitus; Diagnosis; Drosophila genus; Funding; Glucose; Glycoconjugates; Gram-Negative Bacteria; Granuloma; Growth; HIV Infections; Health; Heart Diseases; Human; Hybrids; Hydrolysis; Insulin; Ions; Islet Cell; Islets of Langerhans; Laboratories; Lipid Biochemistry; Lipids; Measurement; Mediator of activation protein; Medicine; Metabolic Diseases; Modeling; Molecular; Mus; Mycobacterium tuberculosis; National Institute of Diabetes and Digestive and Kidney Diseases; Nutritional Study; Parasites; Pathogenesis; Patients; Pattern Recognition; Phospholipids; Property; Reaction; Research; Research Personnel; Research Training; Resources; Role; Salmonella; Scanning; Site; Source; Specimen; Sphingolipids; Stress; System; Tissues; Toxic effect; Universities; Virulence; Washington; Wisconsin; atherogenesis; base; cell envelope; glucose tolerance; human disease; improved; insight; instrument; insulin secretion; killings; mass spectrometer; microorganism; nano; neuromechanism; programs; public health relevance; research study

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.

描述（由申请人提供）：我们建议以生物医学重要的复合脂质的LC/MS/MS分析来获取应用的生物系统Sciex QTRAP 5500杂交三杆三极离子离子陷阱质谱仪（MS）。该程序将受益于这种当代仪器的灵敏度和多功能性，该工具可以用作三倍四极杆，能够执行串联扫描模式，这些模式在我们对生物标本中脂质的分析中证明了无价之宝。我们现有的三倍四极杆MS是一种较旧的工具，它变得难以维护，并且缺乏当代工具的敏感性。所请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，从而允许其在串联四极杆型构型中使用，该配置允许极高灵敏度MSN实验进行脂质结构测定。请求的仪器将放置在华盛顿大学医学系MS工厂的站点1中，该设施是NCRR支持的WU生物医学MS资源（P41-RR00954）的一个地点，也是WU糖尿病研究与培训中心（DRTC，p60-DK20579）（WU NUTIN CLINCLITIN（WU NUTRITIC）的核心MS实验室（CN） NIDDK支持的P30-DK56341）。因此，该设施为NIH资助的各种研究人员提供服务。该仪器将配备与纳米HPLC相连的纳米喷雾源，该系统将为与代谢性疾病的发病机理（如糖尿病及其复杂性）相关的复杂脂质分子的分离和分析提供一个平台，以使其与HIV/AIDS的艾滋病相互作用，以使神经生理学的组合人群的特征构成的人类的特征构成的人类的特征构成人类的特征构成的人类群体的特征性构成人类的特征群体的特征构成人类的特征群体的特征性的人类群体的特征构成的人类群体群体的特征性人物群体的特征构成人类的特征群体的特征构成人群的特征构成人群的特征构成人群。毒力。一个具体的目的是进一步对研究生物医学重要的脂质的许多使用者的NIH资助的研究，并将八个主要项目描述为示例：（1）磷脂衍生的介体和胰岛素的分泌，葡萄糖耐受性，葡萄糖耐受性和动植物（John John Turk，Wu）； （2）磷脂水解和ER应力诱导的胰岛凋亡？ （3）使用果蝇来鉴定葡萄糖毒性的候选修饰符（WU的Thomas Baranski博士）； （4）糖缀合物和鞘脂的作用在动力质体寄生虫生长和毒力中（Wu. Steven Beverley博士和威斯康星州麦迪逊大学的James Bangs博士）； （5）致病性沙门氏菌革兰氏阴性细菌中抗菌素耐药性和毒力的分子碱基（Wu. Eduardo Groisman博士和Univ。Arizona-Tempe的Yixin Shi博士）； （6）结核分枝杆菌细胞壁脂质分子物种和破坏性宿主组织反应的细胞机制（米尔·罗素（David Russell）博士，康奈尔大学（Cornell Univ。） （7）嗅觉模式识别的神经机制（吴，蒂莫西·哈利博士）； （8）HIV感染和脂质生物化学（Kevin Yarasheski博士和Wu的David Clifford博士）。 公共卫生相关性：所需的应用生物科学SCIEX QTRAP 5500质谱仪将用于对生物材料进行测量，这些材料将提供有关与糖尿病，心血管疾病，感染性疾病，脑功能和艾滋病有关的几种重要生物医学问题的信息。其中包括调节分泌胰岛素β细胞功能和存活的机制，病原微生物的细胞表面的特性，这些细胞表面控制了其感染和杀死人的能力，以及为什么艾滋病患者过早发展心脏和血管疾病。这些信息将提供有关开发新方法来诊断和治疗人类疾病的信息，从而改善人类健康。