Regulation of proliferation and differentiation is a fundamental challenge for multicellular organisms. The decision between alternative cell fates is therefore tightly controlled by cellular signaling. During the past decades, the central components of the signaling machinery have been identified. The challenge we are facing now is to understand how signaling networks act dynamically in living cells and how they intersect with each other to control the physiological response of a cell. Since signaling networks contain complex, non-linear interactions that are difficult to understand intuitively, it will be important to use an interdisciplinary approach, combining quantitative experiments and theoretical analysis. As cellular decisions often vary even in genetically identical cells depending on the initial conditions and the micro-environment, we have to measure signaling on the level of individual cells.In the proposed project, we will investigate the TGFbeta pathway, a central growth-inhibitory pathway in epithelial cells. We will acquire quantitative data with high temporal and spatial resolution using time-lapse microscopy of live fluorescent reporter cells and combine it with mathematical modeling. Using this approach, we will determine how the structure of the network shapes its dynamic response, how activation of the signaling pathway is translated into changes in cellular physiology and how TGFbeta interacts with other networks to control cell fate. The resulting mechanistic understanding will enable us to manipulate cell decisions in-vivo and develop therapeutic interventions to regain control over aberrant signaling processes diseased cells.After a postdoc at Harvard Medical School, the applicant is moving back to Europe to start a career as an independent researcher in Germany. Funding of the proposed research will provide significant support for the reintegration process and will foster the transfer of knowledge to the European research community.