Our main scientific interest is to understand the mechanisms by which cells convert the information of extracellular signals, e.g. hormones, growth factors or antigens, into intracellular signals and how these events steer physiological and pathological processes. In particular, we are interested in the mechanisms underlying the fine-tuning of the Mitogen-activated protein kinase (MAPK) and Phosphatidyl-Inositol-3 Kinase (PI-3K) pathways. These pathways play a pivotal role in growth control and differentiation and are often dys-regulated in various human diseases. Although the core components of these pathways have been identified by now, we are still far away from a thorough understanding as to how these signalling elements are fine-tuned, in particular under physiological conditions. Indeed, recent Systems Biology approaches have revealed that, at the post-translational level, these core components are regulated by a plethora of ill-defined protein-protein interactions, feedback loops and crosstalk events (Fig. 1). Consequently, a major challenge for Systems Biology will be the identification of these events, their quantitative spatio-temporal description and ultimately their mathematical modelling.

We are employing a bottom-up approach in that sense that we map the post-translational modification, e.g. phosphorylation, and protein-protein interaction events in space and time for certain signalling elements. These elements, often called hubs, have been identified by genetic approaches as particularly important molecules. Using various complementary technical approaches, we further characterise the signalling pathways controlling these phosphorylation events and protein-protein interactions. We expect that these studies will provide us with a deeper insight into the regulation of these pathways and will impact life sciences in two major ways: Firstly, this knowledge will eventually allow for a more accurate modelling of signalling pathways that are already used for paradigm development in Systems Biology and to this end we aim to interact with modelling experts to establish more refined models of these signalling pathways. Secondly, this knowledge is of growing importance for various clinical disciplines, e.g. to understand the mechanisms of diseases, to identify novel drug targets, to identify proteins with prognostic value for the assessment of drug efficacy and side effects and to steer cellular development in regenerative medicine.

For a more detailed general overview of our research interests, please see publications 12, 13, 14 and 15.