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）：我们建议获得Applied Biosystems Sciex QTRAP 5500混合三重四极杆线性离子阱质谱仪（MS），用于生物医学重要复合脂质的LC/MS/MS分析。该程序将受益于这一当代仪器的灵敏度和多功能性，该仪器可以作为三重四极杆操作，能够执行串联扫描模式，这在我们分析生物标本中的脂质中已被证明是非常宝贵的。我们现有的三重四极质谱仪是一种较旧的仪器，越来越难以维护，并且缺乏现代仪器的灵敏度。所要求的仪器的第三个四极杆也可以作为线性离子阱（LIT）操作，允许其在串联四极杆-LIT配置中使用，该配置允许用于脂质结构测定的极高灵敏度MSn实验。要求的仪器将放置在华盛顿大学（WU）医学系MS设施的研究中心1，该研究中心是NCRR支持的WU生物医学MS资源的一个研究中心（P41-RR 00954），也是WU糖尿病研究和培训中心的核心MS实验室（DRTC，P60-DK20579）和由NIDDK支持的WU临床营养研究单位（CNRU，P30-DK 56341）。因此，该设施为这里和其他地方的NIH资助的研究人员提供服务。该仪器将配备与纳米HPLC接口的纳米喷雾源，该系统将提供一个平台，用于分离和分析与代谢疾病（如糖尿病及其并发症）发病机制相关的复杂脂质分子，用于HIV/AIDS，用于神经生理学研究，并用于表征控制其毒力的病原微生物细胞包膜组分。一个具体的目标是进一步的NIH资助的研究，我们的MS设施的许多用户谁研究生物医学上重要的脂质，和八个主要项目描述在本申请中作为例子：（1）磷脂衍生的介质和胰岛素分泌，葡萄糖耐量和动脉粥样硬化（博士约翰土耳其，吴）;（2）磷脂水解和ER应激诱导的胰岛细胞凋亡？细胞（Dr. Sasanka Ramanadham，WU）;（3）使用果蝇鉴定葡萄糖毒性的候选修饰剂（托马斯Baranski博士，WU）;（4）糖缀合物和鞘脂在动质体寄生虫生长和毒力中的作用（Steven Beverley博士，WU和James Bangs博士，威斯康星大学麦迪逊分校）;（5）致病性沙门氏菌革兰氏阴性菌的耐药性和毒力的分子基础（Eduardo Groisman博士，WU，和Yixin Shi博士，Arizona-Tempe大学）;（6）鼠肉芽肿模型中结核分枝杆菌细胞壁脂质分子种类和破坏性宿主组织反应的细胞机制（大卫罗素博士，康奈尔大学）; (7)嗅觉模式识别的神经机制（Timothy Holy博士，WU）;（8）HIV感染和脂质生物化学（Kevin Yarasheski博士和大卫Clifford博士，WU）。 公共卫生关系：所要求的Applied Biosciences Sciex QTRAP 5500质谱仪将用于对生物材料进行测量，这些生物材料将提供与糖尿病、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。这些包括调节分泌胰岛素的β细胞的功能和存活的机制，病原微生物的细胞表面的特性决定了它们感染和杀死人类的能力，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见解，从而改善人类健康。