Cellular signalling networks

Coordinator:    Prof. Dr. Reinhold Schäfer
Institution: Institut für Pathologie, Charité Universitätsmedizin Berlin
Subproject 7 provides the cell biological complementation of a global search for cancer genes by mutational analysis, protein-protein interaction studies and of mathematical modelling of complex processes within cancer cells. The biological role of cancer-promoting genes (oncogenes) and of cancer-constraining genes (tumor suppressor genes) is being investigated in appropriate cell culture models. Typically, a candidate oncogene recognized by frequent mutation and over-expression in cancers, is incorporated into a phenotypically normal precursor cell line and its product is amplified strongly. The oncogenic function of the candidate gene will become evident by cellular transformation characterized by enhanced growth, increased mobility or by anchorage-independent growth, a feature that reflects the growth of cancer cells in an organism. In addition, we investigate if and how the activity of the transferred protein perturbs the intracellular network of signalling processes, which shape the communication between external substances (e.g. growth factors, hormones) and the intracellular control center.Tumor suppressor genes can be investigated in a similar approach. However, the biological features expected of them are growth inhibition, cell death and loss of cellular mobility and anchorage-independence. In some cases, it is desirable to assay tumor suppressor activity in direct comparison with an oncogene. For this purpose, both factors are transferred into normal cells and the effects on growth are tested. An alternative to the gene transfer experiments is a widely used approach called RNA interference. This mechanism of gene regulation was originally discovered in lower organisms and plants and allows knocking-down any gene activity in cell culture and in some organisms including mammals. Thus, the effect of gene ablation can be investigated within the entire system of cells. Overall, we expect to better understand the role of already known players in the cancer network at the systems level and to establish a genome-wide catalogue and function atlas of all factors involved.

Additional relevant Internet link:
The Mutanom project
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