PD Dr. Ursula Klingmüller, DKFZ Heidelberg (Deputy Coordinator)
The network concentrates on signaling pathways that play an essential role in the cellular decisions between proliferation, differentiation and death. Alterations in these signaling pathways and connected gene regulatory networks can change cellular decisions and thereby trigger the onset of tumor formation. While multiple pathway components have been studied in detail in many cancer types, it remains unresolved how information is processed and how cells decide whether to respond with proliferation or differentiation or survival. To elucidate the functional role of changes in cancer cells and predict targets for efficient intervention, we use a Systems Biology approach combining the identification of novel signaling components by genome-wide RNAi and protein-protein interaction screens with quantitative data generation and dynamic pathway modeling. Special foci of SBCancer are the interactions of tumor cells with their surrounding tissue and how cancer cells react differently to death-inducing and other stimuli. This model-based understanding of signaling in cancer will be used in pilot projects for translational research applications.
The generation of data suitable for mathematical modeling in the biomedical projects is supported by a technology platform providing facilities for large-scale screening of cellular networks, quantitative proteomics and multi-parameter imaging. Besides large-scale analysis of protein function by RNAi knockdown and protein-protein interaction screens, novel methods for the genome-wide quantification of de novo synthesized RNA are used to facilitate the genome-wide identification of gene regulatory networks. The development of intracellular gene-probes will allow monitoring the induction of targets genes at the single cell level.
General methods for model inference, model analysis, mathematical modeling, numerical simulation and optimization are being developed centrally and are closely interlinked with other modeling activities within the Helmholtz Alliance on Systems Biology.
The following institutions take part in the overall 33 research groups: