Dynamics and evolution of metabolic networks
Group leader: Markus Ralser | The Francis Crick Institute, London, UK

We work on the dynamic nature of the metabolic network, and how it emerged in evolution. Located at the Francis Crick Institute, we address the problem by combining techniques of functional genomics with quantitative mass spectrometry, and partially by reconstructing the chemistry underlying metabolism in the test tube. To the key discoveries of the laboratories count the glycolysis/pentose phosphate pathway transition that protects cells from oxidative stress, the first description of a non-enzymatic glycolysis and pentose phosphate pathway that may serve to explain the origin of central metabolism in early evolution, and the completion of a genome-scale functional metabolomic map that assigns a role in metabolism to about 1/3rd of all genes in the genome.
Selected references
  • Keller MA, Kampjut D, Harrison SA, Ralser M. Sulfate radicals enable a non-enzymatic Krebs cycle precursor. Nat Ecol Evol. 2017 Mar 13;1(4):83.
  • Messner CB, Driscoll PC, Piedrafita G, De Volder MFL, Ralser M. Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):7403-7407.
  • Mülleder M, Calvani E, Alam MT, Wang RK, Eckerstorfer F, Zelezniak A, Ralser M. Functional Metabolomics Describes the Yeast Biosynthetic Regulome. Cell. 2016 Oct 6;167(2):553-565.
  • Ralser M. The RNA world and the origin of metabolic enzymes. Biochem Soc Trans. 2014 Aug;42(4):985-8.
  • Grüning NM, Rinnerthaler M, Bluemlein K, Mülleder M, Wamelink MM, Lehrach H, Jakobs C, Breitenbach M, Ralser M. Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells. Cell Metab. 2011 Sep 7;14(3):415-27.