Deciphering metabolism with Sandrien Desmet
Exploring metabolomics with Sandrien Desmet of the VIB Metabolomics Core Ghent
November 14, 2024
Every second, countless chemical reactions power the processes that keep us alive. From breaking down food for energy to detoxifying harmful substances, our cells are constantly producing and using tiny molecules called metabolites. These metabolites are the byproducts of metabolism – the chemical engine that drives all living organisms.
Just as genomics decodes our DNA blueprint and proteomics maps proteins, metabolomics zooms in on the metabolome, the complete collection of small molecules, or metabolites, that drive essential biological processes. Think of the metabolome as a library, with each metabolite representing a book that tells the story of an organism’s health and disease. In humans, it exposes health conditions, nutritional states, and disease pathways. In plants, metabolomics helps us understand growth processes, stress responses, and even how they communicate with their environment. Metabolomics also provides scientists with a deeper understanding of how environmental changes - such as pollution or climate shifts - affect entire microbial communities.
By analyzing the metabolome, scientists get a real-time snapshot of what's happening inside cells. What makes metabolomics so powerful is that it looks at the big picture of how organisms function, instead of focusing on a single process. This integrated approach unlocks secrets across the living world and provides insights that can transform everything from sustainable agriculture to improved human health.
But let’s ask the experts.
Sandrien Desmet is a metabolomics expert who works at the VIB Metabolomics Core Ghent. Following a scientific journey that took her from drug screening to the metabolism of aromatic compounds in maize and poplar, we could not have asked for a better guide.
Hello, Sandrien. How did you get involved in metabolomics and what drew you to this field?
My journey into the world of metabolomics began with a deep-rooted fascination for analytical and organic chemistry in high school. This led to a degree in biochemical engineering technology at the University of Ghent, where I became interested in the technical aspects of the field. During the final year, I interned at the National Institute for Criminalistics and Criminology (NICC) in Brussels, where I was introduced to toxicological screening, working with post-mortem samples – a thrilling experience that opened my eyes to the real-world applications of biological and chemical analysis.
This hands-on experience strengthened my desire to apply analytical techniques to biological systems. I pursued a PhD in the Lab of Prof. Wout Boerjan (VIB-UGent Center for Plant Systems Biology), guided by Dr. Kris Morreel. It was here that I truly discovered my passion for plant metabolomics, a field that continues to captivate me. Plants produce an astonishing array of specialized metabolites with diverse applications for society. Yet, many of these metabolites remain underexplored. My research focused on elucidating the specialized metabolome of poplar and maize, and I developed both dry and wet lab tools for the structural characterization of their unknown metabolites.
In 2021, I joined the VIB Metabolomics Core, headed by Geert Goeminne, as an expert. This role has allowed me to work with a diverse array of samples across various projects. Each day presents new challenges and learning experiences. Through each step of this journey, my enthusiasm for metabolomics has only deepened, and I remain excited about the potential this field holds.
What does your work look like? What kind of techniques and technologies do you often use?
My work typically starts with an intake meeting with the scientist to discuss the biological question they want to answer. We explore their samples and identify which compound classes might be of interest. With this information, we provide support for experimental setups, sample preparation, and guide them in deciding whether to pursue a targeted or untargeted approach. We also assist in selecting the most suitable analytical techniques for their specific needs.
Depending on the research question, samples are then analyzed using one of our high-resolution Gas Chromatography-Mass Spectrometry (GC-MS) or high-resolution Liquid Chromatography-Mass Spectrometry (LC-MS) instruments. Following the analysis, we process the data, perform statistical analyses, annotate the metabolites, and assist researchers with the biological interpretation of the results.
This workflow represents our typical analytical setup. However, some researchers are interested in a preparative setup. In these cases, we purify compounds of interest from complex biological samples. These purified compounds can then for example be supplied to cell cultures to assess their effects, or they can be further analyzed using Nuclear Magnetic Resonance (NMR) for structural identification, which is different from the structural characterization achieved through mass spectrometry. Unlike mass spectrometry, NMR provides deeper insights into a molecule’s 3D configuration.
Given the wide range of projects - from plant samples to animal and microbial samples - my day-to-day activities are quite varied. The approach depends on the specific project, which makes my work both challenging and rewarding. Each research question pushes me to adapt and think critically, so that no two days are the same.
Can you tell us a little bit about some VIB research the Metabolomics Core Ghent has contributed to?
Absolutely! The Metabolomics Core Ghent has been pivotal in several innovative research projects. One notable collaboration involved a study led by Christopher (CJ) Anderson and colleagues. They demonstrated that purine-containing metabolites released from dying epithelial cells significantly influence gut microbial communities, specifically Enterobacteriaceae.
In this study, we performed discovery metabolomics on supernatants from epithelial cells treated with various chemotherapeutics that induce cell death in the absence of bacteria. We identified a range of enriched metabolites across the three cancer drug treatments. Our metabolomics expertise was crucial in uncovering these biochemical interactions and advancing our understanding of disease mechanisms and treatment effects.
In addition, we’re actively involved in numerous projects within the VIB-UGent Center for Plant Systems Biology. For example, sesquiterpene lactones are the compounds responsible for the bitter taste of food crops like industrial chicory and witloof. We performed comparative metabolomics on N. benthamiana leaves infiltrated with different candidate sesquiterpene synthesis genes, and successfully identified several functional paralogs involved in sesquiterpene biosynthesis. These findings were further validated through discovery metabolomics on mutant industrial chicory lines, which showed a significant reduction in sesquiterpene lactones. Coming soon, engineered chicory with modified bitterness?
In another project, Lennart Hoengenaert and colleagues engineered Arabidopsis to produce lignin containing an alternative monomer, scopoletin. The lignin molecule is a major factor limiting the conversion of lignocellulosic biomass (plant material) into fermentable sugars. The conversion efficiency of the scopoletin-overproducing Arabidopsis lines was 40% higher than that of the wild type, making it an interesting alternative feedstock for biomass processing. We performed both targeted and discovery metabolomics to assess the overall effect of this mutation on Arabidopsis phenolic metabolism and the lignin monomers specifically.
These examples illustrate the many opportunities metabolomics offers to advance our understanding of complex biological systems and improve various applications in agriculture, medicine, and sustainable energy.
The Metabolomics Core has also a site in Leuven. How do you collaborate with your colleagues in Leuven?
The VIB Metabolomics Core in Leuven originally focused on primary metabolism, while our team in Ghent focused on (plant) specialized metabolism. Over time, the Leuven core has gained a strong reputation for its expertise in tracer metabolomics, a technique that uses isotopically labeled compounds to track metabolic pathways and dynamics.
In contrast, the Ghent core mastered a pipeline for untargeted (discovery) metabolomics to detect and characterize a wide range of metabolites in a biological sample without prior knowledge. For standard targeted projects, researchers can choose the location based on geographical convenience.
The collaboration between the Ghent and Leuven sites is key to our collective success. We work together closely to leverage our complementary expertise and exchange knowledge, methodologies, and insights while sharing state-of-the-art instrumentation and troubleshooting any technical challenge. This strong collaboration ensures that both sites remain at the forefront of metabolomics research, continually advancing our understanding of metabolic processes.
Are there local initiatives or events for researchers interested in metabolomics?
Definitely! Engaging researchers in metabolomics is a top priority for us. Currently, we’re developing a comprehensive workshop series on discovery metabolomics, designed to provide both essential knowledge and hands-on experience. This series will cover an in-depth introduction to the field, including both theoretical insights and practical sessions on sample preparation, LC- and GC-MS analysis, and data pre- and post-processing. We also actively encourage researchers to reach out with any questions or for guidance.
This year, we hosted the Young NMC Symposium in Ghent, which provided a platform for young scientists working in the Benelux region to showcase their work and connect with peers and experts. The symposium was a great success, featuring a fantastic lineup of presentations, posters, and discussions focused on computational metabolomics, metabolomics core facilities, and biomedical applications of metabolomics. Plans are already in place to organize the next Young NMC Symposium.
In addition, I’m involved in organizing the upcoming European School for Metabolomics, set for 2026. This event aims to bring early-career researchers from across Europe together to explore the latest advancements and ongoing challenges in metabolomics. With expert-led sessions on MS, NMR, fluxomics, bioinformatics, and data processing, the school will offer a deep dive into the technical and scientific aspects of the field. Initiatives like these are vital for advancing metabolomics and cultivating the next generation of experts in the field.
What are some up-and-coming techniques in metabolomics you’re excited about and how do you see the role of metabolomics evolving in the next 5-10 years?
It’s hard not to consider the impact of machine learning (ML) on the life sciences, and metabolomics is no exception. One of the major bottlenecks in the metabolomics research field, especially in discovery metabolomics, is identifying and annotating unknown metabolites. This challenge arises from the extensive chemical diversity and complexity of metabolites, combined with the limitations of current analytical and computational methods.
Traditionally, structural identification of unknown metabolites requires running reference standards on the same instrument used for analysis or using NMR. But such reference standards are only available for a limited fraction of the over one million (!) estimated metabolites, and NMR is constrained by its limited sensitivity. The alternatives, spectral matching and manual interpretation of mass spectra, are hindered by the lack of comprehensive databases and the labor intensity of manual interpretation
ML and artificial intelligence (AI) offer great opportunities to revolutionize metabolomics, particularly in the identification and annotation of unknown metabolites. ML algorithms can automatically extract relevant features from MS data, reducing the need for manual intervention and increasing throughput. AI models can predict the structures of unknown metabolites based on their spectral data, learning from large datasets to improve their accuracy over time.
We have become increasingly involved in large-scale metabolomics projects that would benefit from and could contribute to these computational developments. One example is the ERC-funded POPMET project led by Prof. Wout Boerjan, which focuses on large-scale metabolite identification, mapping metabolic pathways, and linking these pathways to specific genes within Populus (poplar) across 650 genotypes sourced from Europe’s major rivers. The extensive data generated by projects like these will further refine and strengthen ML and AI models, advancing their precision and applicability across metabolomics. Additionally, AI can integrate metabolomics data with other omics data (genomics, proteomics, etc.) to provide a more comprehensive understanding of biological systems and improve metabolite identification.
In parallel, advances in spatial and single-cell metabolomics are pushing the field toward more location-specific and cellular-level insights. Spatial metabolomics allows us to map metabolite distributions within tissue, revealing metabolic changes in specific regions or cell types. Single-cell metabolomics goes even further, offering metabolite profiles at the individual cell level, which is critical for understanding cellular diversity and adaptation.
Looking ahead, I believe that these advancements in ML, AI and sensitive technologies, will add another layer of understanding to metabolomics.
Thank you, Sandrien!
If you are a researcher who is interested in natural compound discovery, get in touch with Sandrien and her colleagues!
The VIB Metabolomics Core Ghent is one of VIB's 14 Core Facilities, which provide expertise, research support, and specialized equipment. The Core Facilities are part of VIB Technologies.
Do you want to be part of this adventure? The Metabolomics Core Ghent is looking for a new Expert to join the team!
