Exploiting ion mobility and high performance mass spectrometry for in-depth characterization of neuropeptides in hypoxia and pH stress

利用离子淌度和高性能质谱法深入表征缺氧和 pH 应激下的神经肽

• 批准号: 1710140
• 负责人: Lingjun Li
• 金额: $ 42.5万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710140&HistoricalAwards=false
• 关键词: Exploiting; ion; mobility; performance; mass

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Lingjun Li at the University of Wisconsin, Madison, is developing new mass spectrometry-based technology to study neuropeptide changes involved in environmental stress. Professor Li and her team focus on the study of how the structures and the concentrations of neuropeptides in a crab change under the lack of oxygen (hypoxia) or under acidic or basic conditions (pH stress). As neuropeptides represent one of the most diverse and essential classes of molecules that regulate various physiological processes, new approaches and techniques are needed to enable a more complete description of these signaling molecules and quantify their changes in response to environmental stressors. Professor Li and her group develop a set of tools based on ion-mobility mass spectrometry to separate different peptides of different size-to-charge ratios. Cataloging different peptides detected will then help to understand their roles in the brain. The funded research takes advantage of the power of analytical chemistry tools to advance neuroscience research. It provides excellent training opportunities to graduate students and undergraduate students in Professor Li's group to pursue a research career at the interface of chemistry and neuroscience. This project seeks to exploit novel use of the powerful ion mobility mass spectrometry (IM-MS) technology to address several remaining technical challenges facing neuropeptide research. Specifically, Professor Li and her team are funded to develop a novel multi-pronged approach based on IM-MS coupling to microseparations, high-performance MS, and molecular dynamic simulations for large-scale discovery, quantitation and structural elucidation of neuropeptides. They plan to improve methodologies for ion mobility assisted large-scale peptidomic analysis and accurate quantitation, its coupling to various microseparation platforms and mass spectral imaging for comprehensive neuropeptide analysis. Furthermore, they will develop a unique IM-MS based strategies to probe novel posttranslational modifications (PTMs) of neuropeptides such as D/L-peptide epimers and O-linked glycosylation. The new methodology is to improve neurochemical signaling analysis in response to hypoxia and pH stress. The technological advancements resulting from this proposal will be applicable to large-scale analysis of biochemical and peptidergic signaling in many nervous systems, including humans. The molecular insights gained from probing neurochemistry in response to stress could lead to a better understanding of neuroendocrine regulatory mechanisms involved in adapting to environmental stress, a process that is highly conserved among all organisms to maintain their survival in the face of both externally and internally generated "stimuli".

在化学系化学测量和成像项目的支持下，麦迪逊的威斯康星州大学的Lingjun Li教授正在开发新的基于质谱的技术，以研究环境应激中涉及的神经肽变化。 李教授和她的团队专注于研究在缺氧（缺氧）或酸性或碱性条件下（pH应激）螃蟹中神经肽的结构和浓度如何变化。 由于神经肽代表了调节各种生理过程的最多样化和最重要的分子类别之一，因此需要新的方法和技术来更完整地描述这些信号分子并量化它们响应环境应激的变化。 李教授和她的团队开发了一套基于离子迁移质谱的工具，以分离不同大小电荷比的不同肽。 对检测到的不同肽进行分类将有助于了解它们在大脑中的作用。 资助的研究利用分析化学工具的力量来推进神经科学研究。 它为李教授团队的研究生和本科生提供了极好的培训机会，以从事化学和神经科学的研究工作。 该项目旨在利用强大的离子迁移率质谱（IM-MS）技术的新用途，以解决神经肽研究面临的几个剩余技术挑战。 具体而言，李教授和她的团队获得资助，开发一种基于IM-MS耦合到微量分离，高性能MS和分子动力学模拟的新型多管齐下的方法，用于神经肽的大规模发现，定量和结构解析。他们计划改进离子迁移率辅助的大规模肽组分析和精确定量的方法，将其与各种微分离平台和质谱成像耦合，以进行全面的神经肽分析。此外，他们将开发一种独特的基于IM-MS的策略来探测神经肽的新型翻译后修饰（PTM），如D/L肽差向异构体和O-连接的糖基化。 新的方法是改善响应缺氧和pH应激的神经化学信号分析。 这项提议所带来的技术进步将适用于包括人类在内的许多神经系统中生化和肽能信号的大规模分析。 从探测神经化学反应的压力中获得的分子见解可能会导致更好地了解神经内分泌调节机制参与适应环境压力，这是一个高度保守的过程，在所有生物体中，以维持他们的生存在面对外部和内部产生的“刺激”。

项目成果

Temporal Study of the Perturbation of Crustacean Neuropeptides Due to Severe Hypoxia Using 4-Plex Reductive Dimethylation

• DOI: 10.1021/acs.jproteome.9b00787
• 发表时间: 2020-04-03
• 期刊: JOURNAL OF PROTEOME RESEARCH
• 影响因子: 4.4
• 作者: Buchberger, Amanda R.;Sauer, Christopher S.;Li, Lingjun
• 通讯作者: Li, Lingjun

Molecular basis for chirality-regulated Aβ self-assembly and receptor recognition revealed by ion mobility-mass spectrometry

• DOI: 10.1038/s41467-019-12346-8
• 发表时间: 2019-11-06
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Li, Gongyu;DeLaney, Kellen;Li, Lingjun
• 通讯作者: Li, Lingjun

Data Independent Acquisition Mass Spectrometry Method for Improved Neuropeptidomic Coverage in Crustacean Neural Tissue Extracts

• DOI: 10.1021/acs.analchem.8b05734
• 发表时间: 2019-04-16
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: DeLaney, Kellen;Li, Lingjun
• 通讯作者: Li, Lingjun

Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System

• DOI: 10.1021/acs.jproteome.9b00525
• 发表时间: 2020-02-01
• 期刊: JOURNAL OF PROTEOME RESEARCH
• 影响因子: 4.4
• 作者: Cao, Qinjingwen;Yu, Qing;Li, Lingjun
• 通讯作者: Li, Lingjun

A Simple and Effective Sample Preparation Strategy for MALDI-MS Imaging of Neuropeptide Changes in the Crustacean Brain Due to Hypoxia and Hypercapnia Stress

• DOI: 10.1021/jasms.9b00107
• 发表时间: 2020-05-06
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Buchberger, Amanda R.;Vu, Nhu Q.;Li, Lingjun
• 通讯作者: Li, Lingjun