Dynamic Control of Metabolic Networks

Our research group works on the interface of biochemistry and systems biology to understand and manipulate the function of metabolic networks. Our main research areas can be categorized as: i) understanding the function of metabolic control circuits, ii) mapping regulatory interactions between metabolites and proteins, and iii) engineering of metabolic control circuits. An important concept in the group is to enforce changes in the metabolic network by genetic perturbations. For point mutations, deletions and insertions we use Cas9-based genome editing methods, and RNA-based methods for perturbations of gene expression. Inducible repression of metabolic genes, for example, allows us to investigate how cells compensate the resulting metabolic bottlenecks and infer regulators of these processes. Time-resolved metabolite and proteome data helps us to distinguish the acute local responses from the more widespread global responses in the metabolic network. Therefore, we use our LC-MS based metabolomics system to measure fluxes and metabolite concentrations, as well as proteomics to probe enzyme expression. Integration of these multi-level data with metabolic models allows us to understand how regulatory mechanisms determine performance and robustness of the metabolic network. The overall goal of our research is to understand fundamental design principles of metabolic control circuits and transfer them to biotechnologically relevant systems. In the long-term we will create synthetic metabolic feedback in order to improve fitness of production strains and thereby maintain high productivity of bioprocesses.

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