High Resolution Metabolomics - generating a step change in metabolomics at Manchester with the Orbitrap IQ-X

高分辨率代谢组学 - 使用 Orbitrap IQ-X 在曼彻斯特实现代谢组学的阶跃变化

• 批准号: BB/X019950/1
• 负责人: Katherine Hollywood
• 金额: $ 131.81万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX019950%2F1
• 关键词: Resolution; Metabolomics; generating; step; change

Metabolomics, the large-scale analysis of as many of the small molecules in a biological system as possible, has become a very important way for us to find out how biology works and how to engineer biology for a healthy and sustainable future. These small molecules include all of the food and energy sources, all of the building block for larger biological molecules, and all of the molecules involved in communication and regulation of biological systems. However, this is a very challenging task, as there can be 1000's of these small molecules in a sample, from very low to high concentrations, and many are very similar. What we need to be able to do is identify and quantify large numbers of metabolites, measure the rate at which they are formed and degraded, and determine the pathways through which this happens, which is especially challenging when metabolites are shared between organisms, such as in the relationship between microbes in the soil and plants. Recent advances in mass spectrometer technology can help us to do this. Mass spectrometry characterizes molecules based on very accurate measurement of their mass and by breaking molecules apart and analysing the fragments, and is one of very few methods that have the potential to provide the data on metabolites that we need. The IQ-X mass spectrometer is a very recent development, and provides very high resolution mass measurement and multiple fragmentation methods in a robust, sensitive and easy to use platform. The very high resolution not allows us to discriminate between very similar molecules, and to calculate their formula based on very accurate mass measurement, but now is good enough to provide access to "fine isotopic structure", information which tells us about the elements that are in the molecules and their relative proportions. This not only helps us to identify the molecules with more confidence, but also may have huge benefits in tracing where molecules go. We can use molecules labelled with stable isotopes, such as 13C and 15N, to trace how these are utilized in a biological system, but dilution through the many pathways that these may be involved in and with the molecules already in the system makes it difficult to follow their fate. The new instrument will allow us to do this much more precisely, and when only small amounts of the isotopes are present in the molecules.The new mass spectrometer, which will be the first of its type in the UK, will have a great impact on many research programs at the University of Manchester (UoM)and across the UK in important strategic areas for the country, such as sustainable biofuels production, the development environmentally friendly chemical production, and reducing global warming by the removal of carbon dioxide from the atmosphere and converting it into useful chemicals. It would also have impact in studying microbiomes and how they form and survive. These microbial communities are found everywhere, from hot springs in Iceland to our skin and gut, and living as communities provides resilience and adaptability, for example for antimicrobial resistance and survival in extreme environments. They are also fundamental to the health of plants, as plants and microbes generally live in synergy and support each other. Understanding how the form and communicate will allow us to better disrupt these in disease, but also engineer these very adaptable systems to achieve our sustainability and environmental goals. It will also help in understanding the mechanisms of disease, for example in understanding how the utilization of fats and lipids changes in Parkinson's disease.

代谢组学，对生物系统中尽可能多的小分子进行大规模分析，已经成为我们了解生物学如何工作以及如何为健康和可持续的未来设计生物学的一个非常重要的方法。这些小分子包括所有食物和能源、较大生物分子的所有构建模块以及参与生物系统通讯和调节的所有分子。然而，这是一项非常具有挑战性的任务，因为在样品中可以有1000个这些小分子，从非常低到高的浓度，并且许多都非常相似。我们需要能够做的是识别和量化大量的代谢物，测量它们形成和降解的速率，并确定发生这种情况的途径，当代谢物在生物体之间共享时，这尤其具有挑战性，例如土壤中的微生物和植物之间的关系。质谱仪技术的最新进展可以帮助我们做到这一点。质谱法基于对分子质量的非常准确的测量以及通过将分子分开并分析片段来表征分子，并且是极少数有可能提供我们所需的代谢物数据的方法之一。IQ-X质谱仪是一款最新开发的质谱仪，它在一个强大、灵敏和易于使用的平台上提供了非常高的分辨率质量测量和多种裂解方法。非常高的分辨率不允许我们区分非常相似的分子，并根据非常精确的质量测量计算它们的分子式，但现在足以提供“精细同位素结构”，告诉我们分子中的元素及其相对比例的信息。这不仅有助于我们更有信心地识别分子，而且可能在追踪分子去向方面有巨大的好处。我们可以使用稳定同位素标记的分子，如13 C和15 N，来追踪它们在生物系统中的使用情况，但是通过这些可能参与的许多途径以及系统中已经存在的分子进行稀释，使得很难追踪它们的命运。新仪器将使我们能够更精确地进行分析，并且当分子中只存在少量同位素时。新质谱仪将是英国首个此类质谱仪，将对曼彻斯特大学（UoM）和英国重要战略领域的许多研究项目产生重大影响，例如可持续生物燃料生产，发展环境友好型化学品生产，并通过从大气中去除二氧化碳并将其转化为有用的化学品来减少全球变暖。它还将对研究微生物组以及它们如何形成和生存产生影响。这些微生物群落无处不在，从冰岛的温泉到我们的皮肤和肠道，作为群落生活提供了弹性和适应性，例如在极端环境中的抗菌素耐药性和生存。它们也是植物健康的基础，因为植物和微生物通常协同生活并相互支持。了解这种形式和沟通方式将使我们能够更好地破坏这些疾病，同时也能设计这些适应性很强的系统，以实现我们的可持续发展和环境目标。它还将有助于了解疾病的机制，例如了解帕金森病中脂肪和脂质的利用如何变化。