Abstract
Metabolomics is the holistic study of endogenous metabolites (lipids, amino acids, sugars, small polar organic acids) and their function within cells, tissues, or organisms. Metabolomics may detect low, but critical effects that are not observed by conventional toxicological methods following exposure to external factors. Exposure to chemical compounds, even at trace levels, may indeed cause measurable changes and biochemical alterations for a given physiological state. To investigate these changes in humans, metabolomics is ideally performed in blood (i.e., plasma, serum) and/or urine.
To cover the vast array of metabolites, the Toxicological Centre (TC) of the University of Antwerp has developed in-house untargeted metabolomics and lipidomics analytical platforms based on liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS) for the analysis of different biological matrices, such as cell extracts and animal tissues1-3. However, there is an urgent need to evaluate and refine these platforms for the analysis of human biological fluids, such as blood and urine. The methods used for human biological fluids may differ from those used for cells and tissues due to a higher complexity and different abundances of various metabolites.
The general objective of the Postdoc Challenge at the TC is to attract a post-doctoral researcher with expertise in the sample preparation, data acquisition and data processing for untargeted metabolomics and lipidomics in human biological samples. Specific objectives are:
- To develop and optimize sample preparation procedures for blood and urine to ensure a wide coverage of endogenous metabolites in these complex matrices
- To tailor the current untargeted metabolomics and lipidomics platforms based on LC-QTOFMS for the specific needs and characteristics of these matrices
- To investigate the usefulness of including additional separation dimensions, such LCxLC or ion mobility in the acquisition of data of higher quality
- To refine the current data processing and metabolite annotation workflows using vendor and open access software tools for the specific needs of human metabolome and lipidome
- To propose a set of QA/QC measures and criteria for the data acquisition and data analysis workflows to ensure the production of high-quality data.
The outcome of this project would be to establish the first untargeted metabolomics/lipidomics platform at UAntwerpen for human biological samples. A high quality and high-end metabolomics platform using state-of-the-art technology and bioinformatics is crucial in order to obtain reliable data which can be used in clinical and biological fields. The applicability potential of such platform is large with direct application in life sciences for the discovery of effect biomarkers associated with a wide variety of diseases (chronic inflammation, metabolic disorders, liver diseases, etc.), but also possibly linked to exposure to chemicals present in our daily life.
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