Acquisition of a High-Field Dual Source FTICR-MS for Pharmaceutical Research

获取用于药物研究的高场双源 FTICR-MS

• 批准号: 7839550
• 负责人: LINGJUN LI
• 金额: $ 207万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7839550
• 关键词: Address; Alzheimer' s Disease; Anesthetics; Asthma; Astrocytes; Biocompatible Materials; Biological; Biological Factors; Biological Markers; Biopolymers; Blood - brain barrier anatomy; Brain; Cell Maintenance; Cell membrane; Clinical; Complex; Development; Disease; Drug Delivery Systems; Evaluation; Event; Faculty; Fluorine; Fourier transform ion cyclotron resonance; Funding; Goals; Health; Housing; Human; Hybrids; Image; Investigation; Label; Length; Limb Development; Lipids; Maintenance; Maps; Mass Spectrum Analysis; Membrane Proteins; Mental Retardation; Modeling; Modification; Nematoda; Neurodegenerative Disorders; Neurons; Neuropeptides; Pharmacologic Substance; Pharmacy facility; Post-Translational Protein Processing; Process; Prostate; Protein Biosynthesis; Proteins; Proteome; Proteomics; Research; Research Personnel; Research Support; Resolution; Role; Sampling; Signal Transduction; Signaling Protein; Source; Stimulus; Techniques; The Sun; Tissues; United States National Institutes of Health; Visual system structure; Yin; base; drug metabolism; experience; feeding; instrument; ionization; leukemia; malignant breast neoplasm; mass spectrometer; member; monocyte; mouse model; novel; protein aminoacid sequence; protein folding; protein protein interaction; response; sleep regulation; small molecule; stem; tumor growth; ultra high resolution

DESCRIPTION (provided by applicant): The goal of this proposal is to obtain funding for a 15 Tesla Bruker SolariX hybrid FTICR mass spectrometer to be housed in the UW-Madison Pharmacy MS Facility. This new instrument will offer several unique features: (1) Ultra-high resolution and high mass accuracy MS, MS/MS, and MSn capabilities; (2) Multiple ionization sources; (3) Enhanced de novo sequencing of peptides with multiple fragmentation techniques; (4) High resolution tissue imaging; (5) Quantitation based on isotopic labeling strategies; and (6) Ability to analyze small molecules as well as full-length proteins. This new instrument will provide advanced MS capabilities to support the research of 28 highly productive NIH-funded investigators with 49 ongoing projects. The use of high resolution MS and tandem MS will help to address multiple levels of human health-related research including, (a) understanding of fundamental biological and disease related processes (neuropeptides involved in feeding stimuli, Dr. Li; neuropeptides and proteins involved in signaling in a nematode model, Dr. Stretton; plasma membrane proteins responsible for maintenance of the blood-brain barrier, Dr. Shusta; proteomic changes in monocytes in response to biomaterials, Dr. Kao; environmental toxicological responses Drs. Elfarra, and Heideman; protein signaling complexes in asthma, Dr. Malter; protein-protein interactions in the visual system Dr. Ruoho; protein folding and biosynthesis, Dr. Cavagnero; prostate development, stem cell maintenance and tumor growth, Drs. Peterson, Bushman and Marker; signaling events in limb development, Dr. Sun; lipids and their role in sleep regulation, Dr. Yin), (b) discovery of biomarkers (for neurodegenerative diseases, Drs. Messing and Li; differences in the brain proteome in mouse models of mental retardation, Dr. Malter; changes in astrocyte secretome associated with neuronal protection, Dr. Johnson), (c) posttranslational modification mapping of proteins in disease process (modifications involved in Alzheimer's disease, Drs. Murphy and Wang; breast cancer, Dr. Xu; leukemia, Dr. Collier), (d) discovery/development of novel natural product pharmaceuticals (validate intermediates and products in the total synthesis of natural products, Dr. Hsung; identify novel polyketides and investigate enzymatic mechanisms of polyketide synthesis, Dr. Shen; structural characterization of glycorandomized pharmaceuticals, Dr. Thorson; structural elucidation of new natural products, Dr. Bugni), (e) improvement of drug delivery (characterization of novel biopolymers for drug delivery, Dr. Kwon; characterization of new fluorine-containing compounds for delivery of anesthetics, Dr. Mecozzi), and (f) clinical pharmaceutical analysis (evaluation of pharmacological profiles of anesthetics, Dr. Pearce; investigation of drug metabolism in clinical samples, Drs. Kolesar, Bailey, and Wilding). Progress on this broad array of projects will be catalyzed by the effective usage of the new instrument through close cooperation among the user groups, Dr. Li, a highly productive faculty member with more than 17 years of experience in biological mass spectrometry, and Dr. Scarlett, the UW-Madison Pharmacy-MS Facility Director. PUBLIC HEALTH RELEVANCE: Successful acquisition of a high resolution Bruker SolariX Hybrid FTICR mass spectrometer will have significant and broad impact on a wide array of biomedical research projects conducted on the health sciences campus at the University of Wisconsin-Madison (UWM). This cutting-edge instrument will provide advanced mass spectrometric capabilities that facilitate deciphering molecular details involved in a broad spectrum of biological processes as well as disease progression, diagnosis and treatment. This instrumentation enhancement will support 30 major and minor users with 49 funded federal grants or contracts, and will accelerate the pace of ongoing research in 13 departments or divisions within five colleges or schools and two centers at UWM as well as being available to the broader scientific community in Madison and the State of Wisconsin.

描述（由申请人提供）：本提案的目标是为一台15特斯拉布鲁克SolariX混合FTICR质谱仪获得资金，该质谱仪将被安置在威斯康星大学麦迪逊分校药房的MS设施中。这台新仪器将提供几个独特的特点：(1)超高分辨率和高质量精度的质谱、质谱/质谱和MSn功能；(2)多电离源；(3)利用多片段化技术增强多肽从头测序；(4)高分辨率组织成像；(5)基于同位素标记策略的定量；(6)分析小分子和全长蛋白质的能力。这种新仪器将提供先进的质谱功能，以支持28名美国国立卫生研究院资助的高生产力研究人员的49个正在进行的项目。高分辨率质谱和串联质谱的使用将有助于解决人类健康相关研究的多个层面，包括：(a)对基本生物学和疾病相关过程的理解(参与摄食刺激的神经肽，李博士；参与线虫模型信号传导的神经肽和蛋白质，Stretton博士；负责维持血脑屏障的质膜蛋白，Shusta博士；单核细胞对生物材料的蛋白质组学变化，高博士；环境毒理学反应埃尔法拉和海德曼；哮喘中的蛋白质信号复合物，Malter博士；视觉系统中的蛋白质-蛋白质相互作用；蛋白质折叠和生物合成，Cavagnero博士；前列腺发育、干细胞维持和肿瘤生长。彼得森，布什曼和马克；肢体发育中的信号事件，孙博士；脂质及其在睡眠调节中的作用，Yin博士),(b)生物标志物的发现(神经退行性疾病，dr。梅辛和李；智力迟钝小鼠模型中脑蛋白质组的差异，Malter博士；与神经元保护相关的星形胶质细胞分泌组的变化，Johnson博士),(c)疾病过程中蛋白质的翻译后修饰作图（涉及阿尔茨海默病的修饰，Johnson博士）。墨菲和王；乳腺癌，徐医生；(d)新型天然产物药物的发现/开发(验证天然产物总合成中的中间体和产品，Hsung博士；鉴定新型聚酮并研究聚酮合成的酶促机制，Shen博士；糖随机化药物的结构表征，Thorson博士；(e)改善药物输送（表征用于药物输送的新型生物聚合物，Kwon博士；表征用于麻醉剂输送的新型含氟化合物，Mecozzi博士）；以及(f)临床药物分析(评估麻醉剂的药理学特征，Pearce博士；研究临床样品中的药物代谢，Bugni博士。Kolesar， Bailey和Wilding)。通过用户组之间的密切合作，有效使用新仪器将促进这一系列广泛项目的进展，李博士是一位在生物质谱方面拥有超过17年经验的高产教师，Scarlett博士是威斯康星大学麦迪逊分校药学-质谱设施主任。

项目成果

Multifaceted investigation of metabolites during nitrogen fixation in Medicago via high resolution MALDI-MS imaging and ESI-MS.

• DOI: 10.1007/s13361-014-1010-0
• 发表时间: 2015-01
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Gemperline, Erin;Jayaraman, Dhileepkumar;Maeda, Junko;Ane, Jean-Michel;Li, Lingjun
• 通讯作者: Li, Lingjun

Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II.

• DOI: 10.1021/acs.biochem.5b01280
• 发表时间: 2016-02-23
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Lu L;Fan D;Hu CW;Worth M;Ma ZX;Jiang J
• 通讯作者: Jiang J

MALDI-MS-assisted molecular imaging of metabolites in legume plants.

MALDI-MS 辅助豆科植物代谢物的分子成像。

• DOI: 10.1007/978-1-4939-1357-2_4
• 发表时间: 2015
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Gemperline,Erin;Li,Lingjun
• 通讯作者: Li,Lingjun

Molecular signatures of sanguinarine in human pancreatic cancer cells: A large scale label-free comparative proteomics approach.

• DOI: 10.18632/oncotarget.3231
• 发表时间: 2015-04-30
• 期刊: Oncotarget
• 作者: Singh CK;Kaur S;George J;Nihal M;Pellitteri Hahn MC;Scarlett CO;Ahmad N
• 通讯作者: Ahmad N

Examination of Endogenous Peptides in Medicago truncatula Using Mass Spectrometry Imaging.

• DOI: 10.1021/acs.jproteome.6b00471
• 发表时间: 2016-12-02
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Gemperline E;Keller C;Jayaraman D;Maeda J;Sussman MR;Ané JM;Li L
• 通讯作者: Li L