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e:Bio / MMML-MYC-SYS: Molecular Mechanisms in Malignant Lymphomas Driven by MYC: A systems biology approach to tumour genetics, evolution, signalling and clinics.
In B-cell lymphomas dramatic effects of the activation of the MYC-transcription factor network were first described about 30 years ago but have so far resisted a clear understanding and lack a specific targeted approach. A systems biological approach is overdue. The spectrum of MYC-lymphomas appear to be the consequence of a multifactor process, which needs to be viewed in a systematic modelling perspective to disentangle the contributions of the MYC- and other mutations, from the features typical for the B-cell lineage and the events occurring in the germinal center hypermutation and affinity maturation.
This consortium research project has the goal to unravel the molecular mechanisms of MYC-activated B-cell lymphomas by an iterative data and model driven process. We will utilize already available molecular-genetic and clinical data from three consortia in whom we participated for many years (MMML, DSHNL, NHL-BFM).
In the iteration process we will generate in a stepwise manner a dynamic multiscale model accounting for (1) the process of MYC-translocation on a genetic level and it impact on cell differentiation, (2) the activation of the transcription factor driven overall gene regulatory network and tissue relevant modular subnetworks, (3) the disease evolution on a tissue germinal center level accounting for effects of additional functional mutations and (4) searching for potential therapeutic targets.