Cell Systems Engineering
The Cell Systems Engineering section combines experimental and modeling approaches to identify leads for improvement of the performance of industrial and natural micro-organisms in biotechnological applications. We aim to push the boundaries of mechanistic and quantitative description of cellular metabolism through combining highly accurate experimental tools with mathematical modelling. Central is the role of model-based approaches, ranging from black-box to detailed kinetic models as well as multiscale modeling of large-scale bioreactors in the context of quantitative experimental data and validation.
Our developed approaches are applied to a variety of microbial cell systems from bacterial to fungal, but also to mammalian cell cultures. Experimental and Modeling expertise:
- Pulse response and step response approaches (with and without stable isotope labeling) to elucidate in-vivo kinetics of metabolic pathways, e.g. using the BioScope mini plug flow reactor
- Scale down experiments to study the effects of the dynamics of the large scale on the physiology and performance of industrial microorganism. like the short-time monitoring of dynamic conditions
- Rapid sampling quenching and sample processing for quantitative targeted metabolomics (see van Gulik).
- LC- and GC-MS based measurement for highly accurate quantification of a broad range (>120) of intracellular metabolites
- Determination of protein levels and analysis of post-translational protein modifications using high-resolution mass spectrometry
- 13C transient state flux analysis at metabolic steady state
- Model based dynamic flux identification using 13C and metabolite measurements
- Agent-based modeling for large-scale bioreactor performance simulation and scale-down design