Mass Spectrometry Based Lipidomics and Metabolomics to Drive Bioscience Discovery

基于质谱的脂质组学和代谢组学推动生物科学发现

• 批准号: BB/S019588/1
• 负责人: William Griffiths
• 金额: $ 95.36万
• 依托单位: Swansea University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS019588%2F1
• 关键词: Mass; Spectrometry; Based; Lipidomics; Metabolomics

Lipids are key components of biological system ranging from plants to mammals. Lipid molecules are critically involved in membrane structures of cells and also provide an energy store and act as signalling molecules within and between cells. Hence, understanding lipid metabolism is important for all areas of the BBSRC remit.Mass spectrometry (MS) represents the primary technology in lipidomics and when combined with liquid chromatography (LC) is suitable for the unbiased identification and quantification of lipids in complex mixtures. Extra dimensions of separation are provided by high resolution MS, where isobaric ions (ions with the same nominal mass but different exact mass) are resolved, and by tandem mass spectrometry (MS/MS) or multi-stage fragmentation (MSn), where characteristic ions are separated from background. A more recent addition to MS-tool box is MS-imaging (MSI) adding further to the available bioimaging technologies. The UK has a burgeoning lipidomic community but lacks a MSI resource. The current proposal is for a high resolution MS instrument with MS/MS and MSn capabilities combined with interchangeable interfaces for high spatial-resolution atmospheric pressure (AP)-MALDI and electrospray ionisation (ESI). The AP-MALDI source offers high spatial-resolution (5 - 10 microm), at the single cell level, while the ESI interface is compatible with other imaging modalities e.g. Liquid Extraction for Surface Analysis (LESA). The instrument will be a resource for BBRSC-remit research and for the UK lipidomic community both academic and industrial. The new instrument will underpin scientific research in several key strategic priority areas for BBSRC, including (1) Healthy ageing across the life course; (2) Sustainably enhancing agricultural production; and (3) The replacement, refinement and reduction (3Rs) in research using animals.

从植物到哺乳动物，脂质都是生物系统的关键成分。脂类分子在细胞膜结构中起着至关重要的作用，它还提供能量储存，并在细胞内和细胞间充当信号分子。因此，了解脂类代谢对于BBSRC研究的所有领域都很重要。质谱仪(MS)是脂类组学中的主要技术，当与液相色谱(LC)相结合时，适合于对复杂混合物中的脂类进行无偏鉴定和定量。分离的额外维度由高分辨率MS提供，其中等压离子(具有相同标称质量但不同确切质量的离子)被分解，以及通过串联质谱仪(MS/MS)或多级碎裂(MSN)，其中特征离子与背景分离。MS-TOOLBOX的最新补充是MS-成像(MSI)，它进一步增加了现有的生物成像技术。英国有一个蓬勃发展的脂肪组学社区，但缺乏MSI资源。目前的建议是提供一种具有MS/MS和MSN功能的高分辨率MS仪器，并结合用于高空间分辨率大气压(AP)-MALDI和电喷雾电离(ESI)的可互换接口。AP-MALDI源在单细胞水平提供高空间分辨率(5-10微米)，而ESI接口与其他成像模式兼容，例如用于表面分析的液体提取(LESA)。该仪器将成为BBRSC-REMIT研究和英国学术界和工业界的一个资源。新仪器将支持BBSRC几个关键战略优先领域的科学研究，包括(1)整个生命周期的健康老龄化；(2)可持续地提高农业生产；以及(3)用动物进行研究的替代、改进和减少(3Rs)。

项目成果

Role of Bile Acid Pathway Intermediates in Pathology of CTX

胆汁酸途径中间体在 CTX 病理学中的作用

• DOI: 10.5281/zenodo.10050200
• 发表时间: 2023
• 作者: Griffiths W

Identification of Unusual Oxysterols Biosynthesised in Human Pregnancy by Charge-Tagging and Liquid Chromatography - Mass Spectrometry

通过电荷标记和液相色谱-质谱法鉴定人类妊娠期间生物合成的异常氧甾醇

• DOI: 10.1101/2022.02.07.478301
• 发表时间: 2022
• 作者: Dickson A

Oxysterol-liver X receptor signaling mediates CYFIP1 regulation of cortical neurogenesis

• DOI: 10.1101/2023.06.23.546272
• 发表时间: 2023-06
• 期刊: bioRxiv
• 作者: D. C. De La Fuente;C. Tamburini;Emily Stonelake;W. Griffiths;J. Hall;M. Owen;D. Linden;A. Pocklington;Yuqin Wang;Meng-Yen Li

Assessment of cholesterol homeostasis in the living human brain.

评估活着的人脑中胆固醇稳态。

• DOI: 10.1126/scitranslmed.adc9967
• 发表时间: 2022-10-05
• 期刊: SCIENCE TRANSLATIONAL MEDICINE
• 影响因子: 17.1
• 作者: Haider, Ahmed;Zhao, Chunyu;Wang, Lu;Xiao, Zhiwei;Rong, Jian;Xia, Xiaotian;Chen, Zhen;Pfister, Stefanie K.;Mast, Natalia;Yutuc, Eylan;Chen, Jiahui;Li, Yinlong;Shao, Tuo;Warnock, Geoffrey, I;Dawoud, Alyaa;Connors, Theresa R.;Oakley, Derek H.;Wei, Huiyi;Wang, Jinghao;Zheng, Zhihua;Xu, Hao;Davenport, April T.;Daunais, James B.;Van, Richard S.;Shao, Yihan;Wang, Yuqin;Zhang, Ming-Rong;Gebhard, Catherine;Pikuleva, Irina;Levey, Allan, I;Griffiths, William J.;Liang, Steven H.
• 通讯作者: Liang, Steven H.

Identification of unusual oxysterols biosynthesised in human pregnancy by charge-tagging and liquid chromatography - mass spectrometry.

• DOI: 10.3389/fendo.2022.1031013
• 发表时间: 2022
• 期刊: FRONTIERS IN ENDOCRINOLOGY
• 影响因子: 5.2
• 作者: Dickson, Alison L.;Yutuc, Eylan;Thornton, Catherine A.;Wang, Yuqin;Griffiths, William J.
• 通讯作者: Griffiths, William J.