Metabolism has been thought of, for a long time, as a static series of biochemical reactions. Recent research, however, reveals that cellular metabolism indeed is highly dynamic, and is implicated in many biologically important phenomena, such as ageing, cellular robustness and adaptation to ever-changing environments.
These properties bring metabolism center-stage both for developing therapies against cancer and neurodegenerative disorders and for understanding the ageing process.
We investigate regulatory functions of the metabolic network and how its dynamics are maintained. A model situation where the metabolome has regulatory function is the adaptation to stress conditions. When cells are exposed to oxidants, when cells age or when a cancer cell starts proliferation, their metabolism changes. We found that under those conditions the metabolic network can reconfigure very quickly, and that metabolism can temporarily adjust without requiring regulation at the transcriptome and proteome layer. There is also evidence that these quick metabolic adjustments can be involved in the induction of transcriptional stress responses.
We address these questions often in the yeast Saccharomyces cerevisiae. Working with this single-cellular eukaryote removes some complexity from our investigations, as a plethora of genetic and biochemical techniques are available. This reduces bias resulting from altered metabolic activity that is found in cell culture systems, allowing us to work with hundreds to thousands of mutants in parallel. To study the metabolic network, we use quantitative mass spectrometry coupled to liquid chromatography for targeted analysis of proteins and small molecules.
Our research team was founded as the 'Molecular Biology of Metabolism group' at the Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics in Berlin in 2007. It then moved to the Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, and is part of the Francis Crick Institute since 2013