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

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种非常重要的方式。这些小分子包括所有的食物和能量来源，所有大生物分子的组成部分，以及所有参与生物系统交流和调节的分子。然而，这是一项非常具有挑战性的任务，因为样品中可能有1000个这样的小分子，从非常低的浓度到很高的浓度，而且许多都非常相似。我们需要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度，并确定它们形成和降解的途径，当代谢物在生物体之间共享时，这尤其具有挑战性，比如土壤和植物中微生物之间的关系。质谱仪技术的最新进展可以帮助我们做到这一点。质谱法通过非常精确地测量分子的质量，并将分子分解并分析其碎片来表征分子，这是有可能提供我们所需的代谢物数据的极少数方法之一。IQ-X质谱仪是最近的一项发展，它提供了非常高分辨率的质量测量和多种破碎方法，在一个强大、敏感和易于使用的平台上。非常高的分辨率不能让我们区分非常相似的分子，也不能根据非常精确的质量测量来计算它们的公式，但现在已经足够好了，可以提供“精细同位素结构”的信息，告诉我们分子中的元素和它们的相对比例。这不仅有助于我们更有信心地识别分子，而且在追踪分子的去向方面也可能有巨大的好处。我们可以使用标记有稳定同位素的分子，如13C和15N，来追踪这些分子在生物系统中的利用方式，但由于这些分子可能参与的许多途径以及系统中已经存在的分子的稀释，使得很难追踪它们的命运。当分子中只有少量同位素存在时，新仪器将使我们能够更精确地做到这一点。这台新型质谱仪将是英国首台此类质谱仪，它将对曼彻斯特大学（UoM）和整个英国在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，以及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群及其形成和生存方式产生影响。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，例如抗菌素耐药性和在极端环境下的生存。它们也是植物健康的基础，因为植物和微生物通常生活在协同和相互支持中。了解它们的形式和交流方式将使我们能够更好地在疾病中破坏它们，同时也能设计出这些适应性很强的系统来实现我们的可持续性和环境目标。它还将有助于理解疾病的机制，例如，了解帕金森病中脂肪和脂质的利用是如何变化的。

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.