At the interface of proteomics and metabolomics

20 March 2019
Despite their differing research disciplines, the VIB Metabolomics Core and the VIB Proteomics Core often cross each other’s paths. Cutting-edge mass spectrometry (MS) takes credit for this: both facilities depend on this rapidly developing technique to measure masses within a sample and, as such, to identify the different molecules it contains.

To gain more insight into how MS furthers scientific discoveries at VIB, we called on three expert technologists, each managing an ‘omics’ core facility: Geert Goeminne (VIB Metabolomics Core, Ghent), Bart Ghesquière (VIB Metabolomics Core, Leuven) and Francis Impens (VIB Proteomics Core, Ghent).

What makes mass spectrometry so valuable, and how is it used in metabolomics and proteomics?
Francis: “At the Proteomics Core, we use MS to measure the masses of protein fragments, called peptides, which allows us to uncover the peptide sequence and hence the protein identity.”

Geert: “The principle is the same for metabolites, even though they’re often a lot smaller than peptides and proteins, and more complex to identify. Besides high resolution and high mass accuracy, our most recent instrument – the Vion-IMS-QTOF – enables us to separate isomeric, isobaric or coeluting compounds on the basis of their shape, size and charge. This technique, called ‘ion-mobility mass spectrometry’, allows for more accurate and more informative data acquisition, which is essential for metabolite identification.”

How does MS enable your overarching research goals?
Francis: “We apply MS to biological samples, such as total lysates of tumor cells, rather than to single molecules. The goal is to identify and quantify as many molecules as possible in a single analysis. Once we’ve mapped out the entire protein image, we can detect the alterations a certain disease involves. In doing so, we work towards a full clinical image to better understand disease mechanisms, to find novel biomarkers for diagnosis or to develop more effective medicines.”

Bart: “The Metabolomics Core dives into understanding the organization of nutrient and waste structures. Using MS, we examine the biochemical paths and identify the purposes which specific pathways are activated for. In this way, we gain insight into the biological functions of proteins and genes.”

Geert: “Comparative metabolic profiling through MS also constitutes a powerful technique to profile thousands of molecules in a single sample and to detect metabolic changes in, for example, ill versus healthy or treated versus non-treated organisms. By identifying the metabolites that have significantly changed, the researcher understands the metabolic regulation and pathways of specific organisms.”

MS clearly reveals new opportunities for further research. Does VIB benefit from this?
Bart: “Yes, definitely. Across VIB core facilities alone, we’re exchanging complementary research results and know-how. Our residues, for example, consist of proteins, which enables us to ‘play the proteomics card’ on the same samples and requires a close collaboration with the Proteomics Core.”

Francis: “Of course, all core facilities are complementary, even though – historically – they cover separate scientific fields. They are the foundation of the research ecosystem at VIB. Since we get plenty of opportunities to team up, we conduct analyses for all VIB centers.”

To what extent are you collaborating withunits outside VIB?
Geert: “Generally speaking, we get plenty of requests from academic and industrial players that want to cooperate with us. In most cases, we introduce them to, and advise them on, the potential added value of MS-based metabolomics for their research projects. Starting from the experiment set-up and sample analysis, we guide them all the way through the generated dataset and provide a comprehensive summary on the statistically processed data.”

Francis: “Since MS is still in its early stages, we’re mostly offering full-service analysis. Once the technology is more mature and user friendly, we will probably gravitate more towards user access services, empowering scientists to do their research all by themselves.”

Despite its newness, MS is a rapidly developing analysis method. How do you manage to finance innovations?
Francis: “If we want to keep up with the latest developments, we need to install new infrastructure every four to five years. Since advanced technologies like MS are expensive, this is only possible as part of an institute that has a funding program. In this regard, VIB holds a unique position in both Belgium and Flanders. Investing in new technologies is part of the vision of our core facility heads.”

Bart: “We also partly depend on external funding. Resources from private foundations and European infrastructure grants recently allowed us to install the latest generation Orbitrap Fusion Lumos mass spectrometers in both the Metabolomics and Proteomics Core. Also, biotech companies notice that we’re building a valuable ecosystem for MS, which intrigues them and gives them an incentive to invest. In turn, we support both local and international biotech players. By installing their MS infrastructure in our core facilities, for example, we hope to create win-win situations.”

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A close-up of the 2-position 6-port switch valve of the Thermo Scientific mass spectrometers​
©VIB_ BartGhesquière