Research group leaders
Markus Ralser
We are interested in the regulatory function of the metabolic network and we investigate how metabolic intermediates are implicated in the control of biological systems. An important situation where the metabolome has regulatory function is the oxidative stress response. Exposure to a toxic oxidant dose leads to a (temporal) reconfiguration of cellular metabolism; as a result, the concentrations of several metabolites are altered; these in turn are implicated in adapting the cell to oxidative conditions.
Answering these research questions is achieved by the combination of yeast and mammalian functional genomics with advanced bioanalytics. We use quantitative mass spectrometry coupled to high-pressure and/or nano-flow liquid chromatography for targeted quantitative and qualitative analysis of small molecules and peptides, and explore functional yeast genetics to detect the genetic interactions.
1. How flexible are metabolic pathways? How do they interact with the regulation of cellular macromolecules?
2. How are metabolic transitions, e.g. the change from oxidation to non-oxidative metabolism regulated?
3. Why do cells age? Which metabolic processes are involed? Can we modulate ageing by changing these processes?
Lab members: Kate Campbell, Floriana Capuano, Michael Mülleder, Jakob Vowinckel
Visit web page at Cambridge Systems Biology Centre
Key publications:
1. Monitoring protein expression in whole-cell extracts by targeted label- and standard-free LC-MS/MS. Katharina Bluemlein and Markus Ralser. Nature Protocols, 2011, 6:6, 859-869, doi:10.1038/nprot.2011.333 Abstract
2. The pentose phosphate pathway is a metabolic redox sensor and regulates transcription during the anti-oxidant response Antje Krüger, Nana-Maria Grüning, Miriam MC Wamelink, Martin Kerick, Alexander Kirpy, Dimitri Parkhomchuk, Katharina Bluemlein, Michal-Ruth Schweiger, Aleksey Soldatov, Hans Lehrach, Cornelis Jakobs and Markus Ralser. Antioxidants & redox signaling, 2011,15(2):311-24. Abstract
3. Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells. Grüning NM, Rinnerthaler M, Bluemlein K, Mülleder M, Wamelink MM, Lehrach H, Jakobs C, Breitenbach M, Ralser M. Cell Metab. 2011 Sep 7;14(3):415-27. PmID: 21907146