Mass Spectrometry Based Lipidomics and Metabolomics to Drive Bioscience Discovery

脂质是从植物到哺乳动物的生物系统的关键组成部分。脂质分子与细胞膜结构密切相关，还提供能量储存，并在细胞内和细胞间充当信号分子。因此，了解脂质代谢对BBSRC的所有领域都很重要。质谱（MS）代表了脂质组学的主要技术，当与液相色谱（LC）结合时，适用于复杂混合物中脂质的无偏鉴定和定量。分离的额外维度由高分辨率MS提供，其中同量异位素离子（具有相同标称质量但不同精确质量的离子）被解析，并且由串联质谱（MS/MS）或多级碎裂（MSn）提供，其中特征离子与背景分离。MS工具箱的一个更新的补充是MS成像（MSI），进一步增加了可用的生物成像技术。英国有一个蓬勃发展的脂质组学社区，但缺乏MSI资源。目前的建议是一个高分辨率的MS仪器与MS/MS和MSn的能力，结合可互换的接口，高空间分辨率的大气压（AP）-MALDI和电喷雾电离（ESI）。AP-MALDI源在单细胞水平上提供高空间分辨率（5 - 10微米），而ESI接口与其他成像模式兼容，例如液体提取表面分析（LESA）。该仪器将成为BBRSC汇款研究和英国脂质组学界学术和工业的资源。新工具将支持BBSRC几个关键战略优先领域的科学研究，包括（1）整个生命过程中的健康老龄化;（2）可持续地提高农业生产;（3）使用动物的研究中的替代，改进和减少（3Rs）。

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.