Delft University of Technology
Julianalaan 67, 2628 BC Delft
Prof. dr. ir. J.J. Heijnen
0031 15 2784341
The group is directed at understanding cell properties in industrially relevant microorganisms such as the central metabolism, compartmentation, transport and regulation. This is done by mathematical modelling combined with precise quantitative measurements.
The group aims at producing a mathematical framework that encompasses all “-omics” levels with especially metabolomics and proteomics measurements. This links metabolic fluxes with expression levels.
The laboratory facilities encompasses an extensive fermentation lab, an analytical lab devoted to the whole range of MS, GC, LC measurements of metabolites and a proteomics lab for the detection and quantitation of proteins with advanced mass-spectrometry (eg Orbitrap, MALDI-TOF) and chromatography (eg nano-UPLC). Special protocols are present to do 13C-based analytical studies.
- metabolomics and metabolic engineering
- the execution of 13C experiments;short-term experiments with the BioScope;quantitative microbial proteomics
- large scale post-translational modification discovery of proteins
- Systems biology of industrial microorganisms (S. cerevisiae, E. coli, P. chrysogenum, A. niger)
- metabolic pathway analysis
- short-term dynamic perturbation studies
- long-term behaviour of microorganisms under varying stress conditions;microbial proteome analysis
Expertise and Track Record
The IDMS method for quantitative metabolomics is internationally unique. The precision of the quantitative metabolomics and proteomics is outstanding. The experience with 13C experimentation and analysis has an internationally recognized standing.
Support track record: On the metabolomics side, we either accommodate visitors from several European countries to do specific fermentation experiments. Also, for example the BioScope for fast dynamic measurements has been made duplicated in or for 4 different institutions. On the proteomics side, the group has operated the analytical hotel function for ‘Quantitative proteomics and peptidomics’ inside the Netherlands Proteomics Centre.
- Taymaz-Nikerel, H., de Mey, M., Ras, C., ten Pierick, A., Seifar, R.M., van Dam, J.C., Heijnen, J.J., van Gulik, W.M., Development and application of a differential method for reliable metabolome analysis in Escherichia coli, (2009) Analytical Biochemistry, 386 (1), 9-19. An example of the quantitative metabolomics with sampling and quenching procedures to freeze instantaneously the cell state to best determine the in vivo intracellular and extracellular metabolite concentrations.
- De Mey, M., Taymaz-Nikerel, H., Baart, G., Waegeman, H., Maertens, J., Heijnen, J.J., van Gulik, W.M., Catching prompt metabolite dynamics in Escherichia coli with the BioScope at oxygen rich conditions, (2010) Metabolic Engineering, 12 (5), 477-487. The design and application of a mini-plug flow reactor to study dynamic responses in the order of the seconds range.
- Cruz, L.A.B., Hebly, M., Duong, G.-H., Wahl, S.A., Pronk, J.T., Heijnen, J.J., Daran-Lapujade, P., van Gulik, W.M. Similar temperature dependencies of glycolytic enzymes: An evolutionary adaptation to temperature dynamics? (2012) BMC Systems Biology, 6, art. no. 151. To understand regulation strategies that underlie microbial temperature responses and adaptation, we studied glycolytic pathway kinetics in Saccharomyces cerevisiae during temperature changes.
- Bener Aksam, E.; Pinkse, M. W.; Verhaert, P. D., Molecular characterization of Saccharomyces cerevisiae alpha-pheromone by mass spectrometry-based peptidomics. FEMS Yeast Res (2013), 13, (3), 350-3. Peptidome analysis of unicellular signalling compounds.
- Liebensteiner, M. G.; Pinkse, M. W.; Schaap, P. J.; Stams, A. J.; Lomans, B. P., Archaeal (per)chlorate reduction at high temperature: an interplay of biotic and abiotic reactions. Science (2013), 340, (6128), 85-7. Proteomics based discovery of key players in metabolic pathways.
The group participated and participates in the Kluyver Centre for Genomics of Industrial Fermentation as partner, the Netherlands Proteomics Centre as technology ‘hotel’, the Netherlands Metabolomics Centre as co-participant. We will be involved with the Dutch TKI’s through various projects in the BE-Basic consortium.