Systems Biology of Genetic Diseases – Mutanom Project
The Mutanom project is an Integrated Genome Research Network (IG)
Funded through the NGFN Plus Research initiative. The IG Mutanom aims to characterise the functional consequences of somatic mutations and to develop models that predict the outcome of such genetic alterations on a molecular pathway level, cellular and organism level. From very early on in this project our results will be translated into the clinical and Public Health sector with the goal to define new diagnostic and therapeutic strategies. At the beginning of the project our effort will concentrate on characterising „driver“ mutations (i.e. mutations that occur in cancer due to selective pressure) that already have been selected from databases and from the scientific literature, which will be characterised in close collaboration among the different subprojects. The consortium has complementary expertises in the fields of proteomics (MPIMG, DKFZ, MDC) functional genomics (MPI-MG, DKFZ) modelling (MPIMG). Clinical partners and companies (e.g. Cellzome) are part of the project and will carry out mass spectrometry analysis, expression profiling, provide tissue samples or clones. Academic experts (SOCMED) will ensure from the early beginning of the project that the translational aspects of the project will be fully exploited.
Workflow and concept of the IG-Mutanom: Functional characterisation of somatic mutations will be carried out in isogenic cell lines whose genetic background has been defined through high-throughput sequencing. In a first step disease relevant mutations are identified from databases as well as through high-throughput sequencing both from cancer tissues as well as established cancer cell lines. Wild type as well as mutant clones (synthetic clones) will be characterised through several complementary assays including an animal model and several genomic and proteomic approaches. These data will be collected for the modelling of the effect of genetic aberrations. Additional information will be gained by perturbing wild type or mutated gene function through chemotheurapeutica or stress cues. Models will predict effects of gene mutations and will be used for the development of optimised preventive and therapeutic strategies on a clinical level.