BIH Metabolomics Platform
The BIH Metabolomics Platform pursues mass spectrometry metabolomics research with clear translational medicine potential. We are particularly interested in heart and brain health and the interaction between the two. If you are interested in working with us, please contact us with full details of your project. We are based in House 64 at the MDC Campus Buch.
Dr. Jennifer Kirwan (since October 2016)
Tobias Opialla (Research fellow in metabolomics)
Raphaela Fritsche (Research fellow in metabolomics)
Yoann Gloaguen (Research fellow in metabolomics bioinformatics, joint position with the BIH bioinformatics core unit)
Mathias Kuhring (Research fellow in metabolomics bioinformatics, joint position with the BIH bioinformatics core unit)
Dai Long Vu (starting Oct 1st 2018)
Mass spectrometry engineer – now recruiting
Prof. Erich Wanker: Department of Neuroproteomics and Molecular Mechanisms of Neurodegenerative Diseases
Prof. Michael Schupp: Institute of Pharmacology
Prof. Mathias Treier: Genetics, metabolic und reproductive dysfunctions
Prof. Joachim Spranger: Endocrinology and Diabetology, speaker CRU steering committee
Preanalytical Processing and Biobanking Procedures of Biological Samples for Metabolomics Research: A White Paper, Community Perspective (for “Precision Medicine and Pharmacometabolomics Task Group”—The Metabolomics Society Initiative), Jennifer A. Kirwan, Lorraine Brennan, David Broadhurst, Oliver Fiehn, Marta Cascante, Warwick B. Dunn, Michael A. Schmidt, Vidya Velagapudi, Clinical Chemistry Jan 2018, clinchem.2018.287045; DOI: 10.1373/clinchem.2018.287045
Fritsche-Guenther, Raphaela, et al. "Alterations of mTOR signaling impact metabolic stress resistance in colorectal carcinomas with BRAF and KRAS mutations." Scientific reports 8.1 (2018): 9204.
Beger, R. D., Dunn, W., Schmidt, M. A., Gross, S. S., Kirwan, J. A., Cascante, M., ... & Broadhurst, D. I. (2016). Metabolomics enables precision medicine:“a white paper, community perspective”. Metabolomics, 12(10), 149.
Henning, P., Kuich, P. H., Hoffmann, N. & Kempa, S. (2014) Maui-VIA: A User-Friendly Software for Visual Identification, Alignment, Correction, and Quantification of Gas Chromatography-Mass Spectrometry Data. Frontiers in bioengineering and biotechnology 2:84 doi:10.3389/fbioe.2014.00084.
Awards and Achievements
Metabolomics Society 2017 Best Review Award: Beger, R. D., Dunn, W., Schmidt, M. A., Gross, S. S., Kirwan, J. A., Cascante, M., ... & Broadhurst, D. I. (2016). Metabolomics enables precision medicine:“a white paper, community perspective”. Metabolomics, 12 (10), 149.
Facilities and capabilities
Metabolomics attempts to undertake a global analysis of all metabolites within a cell or biological system. In translational medicine, it is most frequently used to compare different populations to study disease, identify potentially new diagnostic and prognostic biomarkers and to understand disease processes in more detail. A subsection of metabolomics, called lipidomics, concentrates on analyzing lipids and fats. The mammalian body is host to a large number of individual metabolites, spanning a wide range of physicochemical properties. To be able to measure a broad range of these metabolites from just one sample presents some challenges. The BIH Metabolomics Platform is equipped with some of the latest range of mass spectrometers and separation technologies to enable world class research. Facilities include:
- Leco GCxGC-Electron impact-Time of Flight mass spectrometer, a gas chromatography based system that allows the measurement of small molecules and is especially useful for polar molecules. A previously validated method enabling a quantitative, targeted analysis of up to nearly one hundred defined metabolites involved in central carbon metabolism is possible on this system. Online derivatisation enables samples to be derivatised and then analysed in a timely fashion, limiting the potential for the sample to degrade.
- Thermo Quantiva, a triple quadrupole mass spectrometer allows the measurement of small molecules and lipids. Its fast scanning speeds make it particularly useful for targeted analysis and it can be combined with liquid chromatography for prior separation of complex biological matrices.
- Thermo Q-Exactive (based on Orbitrap technology), a high resolution, highly mass accurate Fourier transformation mass spectrometer that is used for lipidomics and metabolomics analyses. It can be coupled with FAIMS (see below) or liquid chromatrograph for further separation.
- Agilent 1290 two-dimensional liquid chromatography system, for detection, identification and separation of molecules with similar chemical properties: especially useful for lipids
- Biocrates Absolute IDQ p400 HR kit analyses: to enable rapid analyses of up to 365 lipids and 43 small molecules, we have introduced the Biocrates p400 kit into our lab. For more details, please see the Biocrates website
- Owlstone Field asymmetric ion mobility spectrometry, an ion mobility technology that enables separation of compounds based on cross sectional area to enable improved analysis by mass spectrometry of mixed isomeric species
- To support epidemiological size metabolomics studies we have developed a robotic system to facilitate the preparation of the required standard mixtures for metabolomics analyses and to perform the extraction and sample preparation procedures in an automatized way. This robotic system is a significant step towards lab automation, as it includes the handling of solid substances and liquids in a single system specifically designed for our workflows.
https://www.bihealth.org/Precision medicine and metabolomics
Precision medicine is the concept of tailoring the prevention, diagnosis and treatment of ill health in individuals according to their genetics, environment and lifestyle. For example, prognosis and response to certain therapeutic agents in women with breast cancer has been demonstrated to be different dependent on whether they carry a BRCA mutation or not (Smith et al 2012). This ability to more accurately predict and select treatment based on individual differences is likely to improve as our knowledge of the interplay between genetics, environment and lifestyle increases.
Metabolomics and the ability to assess metabolism is of particular interest in the context of precision medicine as it reflects the effects of both genetic predispositions and acute and chronic lifestyle influences. The metabolome adjusts within very short time scales, much faster than alterations seen in the proteome, genome or epigenome and, as such, is probably the closest measurement of phenotype we have.
When designing precision medicine trials, paired samples or a longitudinal time series are often particularly useful. They allow direct comparison and thus more meaningful information about acute physiological states and responses to external interventions compared to other experimental designs. Studying the dynamic responses to diagnostic challenges, e.g. glucose tolerance tests or ADH tests, might eventually enable single sample diagnostics in the future. Personalized monitoring, where individuals are sampled repeatedly over a long time allows an individual to act as their own control and may enable better assessment of why that individual develops disease. Compared to traditional comparative studies involving large numbers of people, longitudinal analysis of an individual (i.e. a targeted n=1 analysis) reduces confounding variables that complicate interpretations of data and might provide an alternative route to biological understanding of diseases (Chen et al., 2012).
Capabilities and Current Developments
- Targeted GC-MS
- Targeted LC-MS/MS
- Untargeted direct infusion mass spectrometry
- Automated sample extraction and derivatisation
We are currently in the process of validating a robotic system for the automated extraction and derivatisation of samples.
- Small volume sample analysis
A reliable and robust targeted analysis of the central carbon chain and associated metabolites can now be performed using only a single drop of capillary blood. This is especially useful for longitudinal monitoring of interventions.
- Maui-VIA a data analysis tool for GC-MS data
is a software tool that enables a fast and precise analysis of GC-EI-MS metabolomics data. This software tool allows the automated analysis of our custom-designed in-house identification and quantification mixtures and includes additional measures for quality control. In 2015 the 1st GC-MS and MAUI-SILVIA user workshop was held. The software tool is declared as an invention at the MDC.