A new line of attack against bacterial and viral infections consists of designing drugs against host proteins that are essential for infection. In order to colonize cells, pathogens subvert the functions of a limited number of host cell receptors, signaling proteins and molecular machines described as the infectome. The aim of the “InfectX” RTD project is to comprehensively identify the components of the human infectome for a set of important bacterial and viral pathogens and to develop new mathematical and computational methods with predictive power to reconstruct key signaling pathways controlling pathogen entry into human cells. The components of the infectome will be identified by combining high-content microscopy-based, genome-wide RNA interference (RNAi) screens with surface and phosphoproteome datasets. Functional and molecular characterization of key signaling components will occur by iterative loops between secondary RNAi screens, biochemistry, multi-dimensional fluorescence microscopy and computational-based pathway reconstruction methods. The refined models will then be used to predict human targets suitable for the development of novel anti-infectives that interfere with pathogen infection in human cells.