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

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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.