ENDOSYS: Systems Biology of Hepatocyte Endocytosis

The EndoSys network will pursue a systems biology analysis focusing on the endocytic pathway and its relationship with signal transduction. To achieve this ambitious goal, the EndoSys network will continue combining bottom-up and top-down approaches both at the theoretical and experimental level, aiming at formulating a mathematical model and simulation platform that describes in quantitative terms endocytosis and signalling in hepatocytes in response to various physiological stimuli. In an iterative process, the modelling partners in the network will develop mathematical models that predict endocytosis and signalling activities in primary hepatocytes. Using a multidisciplinary approach, the development of HC cell-based assays will be combined with HT technologies and automated image analysis to test the predictions of the mathematical models and identify novel regulatory components of the endocytic machinery using bioinformatics and structure prediction analysis. The strictly quantitative data generated by the experimental approaches will fuel new information to the theoretical groups that will help correcting or refining the models. Clearly, for the success of this endeavour it will be essential to integrate these activities with those of the other networks and technology platforms within HepatoSys to improve both modelling and experimental strategies. The EndoSys network will interact with the Regenerating Hepatocytesnetwork (e.g. concerning endocytosis and TGF-β signalling), Detoxification and Dedifferentiation network (e.g. discovery of novel hepatocyte differentiation and toxicity biomarkers), and the Cell Biology platform (e.g. SOPs for methodology, siRNA transfection). It is expected that the activity of the consortium will result in the development of technologies and advancement of science that will not only be relevant for academic research but also bear important implications for industrial applications.