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High definition ion-mobility mass spectrometry and imaging for metabolomics, lipidomics and glycomics

用于代谢组学、脂质组学和糖组学的高清离子淌度质谱和成像

基本信息

批准号：
BB/R013403/1
负责人：
Tony Larson
金额：
$ 86.63万
依托单位：
University of York
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR013403%2F1
关键词：
definition ion mobility mass spectrometry

项目摘要

We propose to purchase a high-end mass spectrometer system that is capable of identifying thousands of unique small molecules at a time. This is achieved by the combination of accurate mass measurements, which enables the calculation of molecular formulae, and the ability of the mass spectrometer to separate molecules on the basis of their mass and shape. This last ability - separation on the basis of shape - is achieved using a technique known as ion mobility, which is not standard on most commercially available mass spectrometers. Ion mobility techniques allow molecules that have identical masses and formulae to be separated. This ability is crucial for the correct identification and measurement of several classes of biologically important molecules, including small molecules, lipids, and carbohydrates. We propose two main front-end interfaces that will make full use of the mass spectrometer's capabilities. The first is an imaging interface, where plant or animal tissue slices can be automatically sampled in a two-dimensional plane to build up a picture of where molecules are localised in the sample. As one input to this imaging pipeline, we will also use the output from our newly acquired, separately funded quantitative phase imaging microscope, which enables cell types and behaviours in tissue slices to be visualised and measured without prior staining or fixing. This pipeline - from visible features to mass spectrometry imaging on the same sample - will enable us to relate visible changes observed within tissues to the underlying biochemical processes. Applications range from tracking drug movements between cell types in medical treatments, to locating the sites of plant cell wall degradation in studies where the focus is on optimizing biofuel generation from waste biomass. The second interface uses separation by high-performance liquid chromatography of biological extracts before the mass spectrometer. This will enable us to characterize very complex mixtures, for example from understanding how the lipid make-up of cell membranes in industrially important microbes contributes to robust fermentation, to measuring fine changes in branched carbohydrate structures that are important signalling and recognition molecules in human disease. A common thread in all the different applications will be the complexity and multi-dimensionality of the data produced. All data will require careful filtering and annotation to provide biologically meaningful conclusions; this is not trivial and more often than not requires significant expert manual input and is a productivity bottleneck. To address this often overlooked area, together with the instrument manufacturers, we are committing resources to develop software tools for efficient data analysis.

我们建议购买一个高端的质谱仪系统，能够一次识别数千个独特的小分子。这是通过结合精确的质量测量来实现的，这使得能够计算分子式，并且质谱仪能够根据分子的质量和形状分离分子。最后一种能力--基于形状的分离--是使用一种称为离子迁移率的技术实现的，这种技术在大多数商用质谱仪上都不是标准的。离子迁移率技术允许分离具有相同质量和分子式的分子。这种能力对于正确识别和测量几类生物重要分子（包括小分子、脂质和碳水化合物）至关重要。我们提出了两个主要的前端接口，将充分利用质谱仪的能力。第一个是成像界面，植物或动物组织切片可以在二维平面上自动采样，以建立分子在样品中定位的图片。作为该成像管道的输入之一，我们还将使用我们新收购的、单独资助的定量相位成像显微镜的输出，该显微镜使组织切片中的细胞类型和行为能够在无需事先染色或固定的情况下进行可视化和测量。这条管道-从可见特征到同一样品的质谱成像-将使我们能够将组织内观察到的可见变化与潜在的生化过程联系起来。应用范围从跟踪药物在医疗中的细胞类型之间的运动，到定位植物细胞壁降解的研究，其中重点是优化从废弃生物质中产生生物燃料。第二个接口在质谱仪之前使用生物提取物的高效液相色谱分离。这将使我们能够表征非常复杂的混合物，例如，从了解工业上重要的微生物中细胞膜的脂质组成如何有助于强大的发酵，到测量分支碳水化合物结构的细微变化，这些结构是人类疾病中重要的信号和识别分子。所有不同应用程序的一个共同点是所产生数据的复杂性和多维性。所有数据都需要仔细过滤和注释，以提供有生物学意义的结论;这不是微不足道的，通常需要大量的专家手动输入，是生产力的瓶颈。为了解决这一经常被忽视的领域，我们与仪器制造商一起投入资源开发软件工具，以实现高效的数据分析。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Acrylic acid and DMSP lyases in the green algae Ulva

DOI：
10.1016/j.algal.2023.103176
发表时间：
2023-07
期刊：
Algal Research
影响因子：
0
作者：
G. Pesante;Edith C F Forestier;Swen Langer;A. Danby;John Angus;Mark J. Gronnow;Joseph P. Bennett;T. Larson;T. Tonon
通讯作者：
G. Pesante;Edith C F Forestier;Swen Langer;A. Danby;John Angus;Mark J. Gronnow;Joseph P. Bennett;T. Larson;T. Tonon

Improved furfural tolerance in Escherichia coli mediated by heterologous NADH-dependent benzyl alcohol dehydrogenases.