Metabolism is the ‘engine’ of microbial live, generating energy and redox equivalents but also precursors for growth. Its sustained operation by large networks of enzymatic reactions forms a complex network that requires fine-tuned regulation. Malfunction of the regulation can lead to accumulation of intermediates and loss of function and decreased fitness (or even death). The network stoichiometry has been studied intensively including the use of metabolic tracer experiments to quantify steady-state fluxes of the network. Identifying the underlying kinetics and understanding the regulatory mechanism of metabolism is the aim of the Wahl group. These insights are then used to design microbial cell factories that operate robust under industrial conditions.
funded by ERA-IB
The project has academic and industrial partners: FZ Jülich, University of Minho, Delft University of Technology, SilicoLife, Metabolomics Discoveries and GENOMATICA. We focus on a molecule that can be used as drop-in chemical for fuels, solvents and polymers, 1,4-butanediol (BDO) and isopropanol. Next to the applied aspects, the project addresses very fundamental questions of metabolic regulation in bacteria. How does metabolism prevent react to sudden changes in the environment. Is there a training effect, especially are cells that have experienced many perturbations ‘fitter’ than ‘untrained’ cells? Which mechanisms are involved in the training phase and how does metabolism adapt to frequent perturbations.
- Metabolic functionality of storage accumulating microorganisms under dynamic environments
funded by SIAM, NWO
In natural environments, organisms with very specific properties dominate in their niche. In this project we focus on organisms that use enhanced carbon storage mechanism as survival mechanism. During feast-famine cycles, which additionally vary between aerobic and anaerobic conditions, organisms that can accumulate glycogen, PHB and polyphosphate have a competitive advantage. Their survival strategy requires enormous metabolic flexibility and efficient ‘switches’ in the different phases. Advanced metabolomics and 13C tracing techniques are applied to identify the metabolic tricks of these microorganisms.
- Escherichia coli redox metabolism
funded by NWO/FAPESP
Together with partners from Universidade de Sao Paulo and Campinas (Brazil) we modify the redox metabolism of E. coli with the aim to ‘reprogram’ the cellular balance between biomass formation and product synthesis. Many metabolic products require reduction equivalents like NADPH and intermediates from central carbon metabolism. As case study we use PHB synthesis which is an established pathway and study the effect of different glycolytic stoichiometries on biomass versus product formation.
The courses I teach cover different aspects of the Life Science and Technology (LST) curriculum as well as post master education (Biotechnology Academy Delft)
I believe that following elements are indispensable for an effective and fun course
- Clear and transparent structure of the content and the grading scheme
- Elements of competition
- Early and sufficient feedback on student activities
- Appreciate and motivate student activity
The content has to stimulate thinking and challenge students. Therefore relevant and challenging assignments are central in my courses. I use group-work to stimulate peer learning. Extensive support and feedback are used to further improve the quality.
For the preparation, communication and execution of course concepts, gamification is applied. The concept values all student’s activities and motivates for active participation. A list of current courses can be found under ‘Teaching’.
- Dr. Stephan Noack, Dr. Marco Oldiges and Dr. Kathrina Nöh Forschungszentrum Jülich GmbH, Germany
- Dr. Isabel Rocha University of Minho, Portugal
- Prof. Bas Teusink (since 2010) VU Amsterdam, The Netherlands
- Prof. Pau Ferrer, Universidad Autonoma de Barcelona, Spain
- Prof. M. Canovas, Universidad de Murcia, Spain
- Dr. C. Danelon, Dr. G. Bokinsky, BioNano TU Delft
Leonor Guedes da Silva successfully defended her PhD thesis: "Life in changing environments: The intriguing cycles of polyphosphate Accumulating organisms". A systems biology study including lots of lab work & computational approaches to connect the genotype to phenotype of environmentally-relevant microorganisms. Read the book <a href="https://repository.tudelft.nl/islandora/object/uuid%3A944a1cc2-9a30-4b84-91b9-5022d689d7f3?collection=research"> here</a>
Dr. Eleni Vasilakou successfully defended her PhD Escherichia coli metabolism under dynamic conditions: The tales of substrate hunting. CONGRATULATIONS!
Mariana Itzel Velasco has won a poster prize at ISBP 2018 in Beijing with her contribution "Coupling Catabolism and Poly-3-Hydroxybutyrate Production in Escherichia coli"
Robin Schumacher (now at A*star institute Singapore) successfully defended his PhD thesis "Metabolic trade-offs arising from increased free energy conservation in Saccharomyces cerevisiae" (available online here). The defense took place 16-10-2018 at aula.
The Wahl group hosted a workshop on Applied Systems Biology with 14 interesting presentations and about 50 participants. Was a nice challenge and fruitful exchange.