Modelling of Biological Networks

Cellular processes are coordinated by networks of interacting molecules, and many diseases are caused by perturbations in these networks. Neither can be fully understood by studying single genes or proteins. To better understand cell function in health and disease, my group analyses the dynamic interplay of cellular components, with special emphasis on how cells sense environmental changes. We apply systems biology approaches, and combine mathematical modelling with quantitative experimental data to understand the wiring and dynamics of signalling and gene regulatory networks.

We use ensembles of single-cell mathematical models to study single-cell variability in signalling networks. Our goal is to understand how cellular networks function reliably despite intracellular stochasticity and fluctuating environments, and how molecular networks can buffer fluctuations to maintain precision and robustness.

Positions held

  • Since 2010: Group Leader, Institute of Molecular Biology (IMB), Mainz
  • 2009-2010: Group Leader ‘Theoretical Systems Biology’, Department of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg
  • 2008-2009: Postdoctoral Researcher, Institute for Theoretical Biology, Humboldt University Berlin


  • 2008: PhD in Biophysics, Humboldt University, Berlin
  • 2004: Diploma in Biochemistry, University of Witten/Herdecke

Recent publications by Stefan Legewie

Enculescu M, Braun S, Setty ST, Zarnack K, König J and Legewie S (2019). Exon definition facilitates reliable control of alternative splicing. bioRxiv, doi: 10.1101/714022

Becker K, Bluhm A*, Casas-Vila N*, Dinges N*, Dejung M, Sayols S, Kreutz C, Roignant JY, Butter F# and Legewie S# (2018). Quantifying post-transcriptional regulation in the development of Drosophila melanogaster. Nat Commun, 9: 4970

Braun S*, Enculescu M*, Setty ST*, Cortés-López M, de Almeida BP, Sutandy FXR, Schulz L, Busch A, Seiler M, Ebersberger S, Barbosa-Morais NL, Legewie S#, König J# and Zarnack K# (2018). Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis. Nat Commun, 9: 3315

Sutandy R*, Ebersberger S*, Huang L*, Busch A, Bach M, Kang HS, Fallmann J, Maticzka D, Backofen R, Stadler PF, Zarnack K, Sattler M, Legewie S#, Koenig J# (2018). In vitro iCLIP-based modeling uncovers how the splicing factor U2AF65 relies on regulation by co-factors. Genome Res, 28(5):699-713

Fritzsch C*, Baumgärtner S*, Kuban M, Steinshorn D, Reid G# and Legewie S#. (2018).  Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting. Mol Syst Biol, 14: e7678

Ghosh B*, Sarma U*, Sourjik V# and Legewie S#. (2018).  Sharing of phosphatases promotes response plasticity in phosphorylation cascades. Biophys J, 114: 223–236

Strasen J*, Sarma U*, Jentsch M*, Bohn S, Sheng C, Horbelt D, Knaus P, Legewie S# and Loewer A#. (2018).  Cell‐specific responses to the cytokine tgfβ are determined by variability in protein levels. Mol Syst Biol, 14: e7733.

Research website