Apoptosis Systems Biology Applied to Cancer and AIDS

An integrated approach of experimental biology, data mining, mathematical modeling, biostatistics, system engineering and molecular medicine.

The APO-SYS consortium aims at obtaining major progress in comprehension of apoptosis (and more generally cell death) in human diseases, by combining a series of systems biology approaches, in silico, in vitro (in organello and in cellula), in vivo and by integrating experimental results with large data sets acquired on tissue samples from patients suffering from diseases that are caused by deregulated apoptosis, in particular cancer and AIDS.

The consortium addresses the striking complexity of human cell death pathways using an integrated method involving high-throughput screening, and ”omics” approaches applied to biological systems and computational modeling leading to accurate and disease relevant in silico models of apoptotic signaling triggered along the two principal pathways, the extrinsic pathways (stimulated by ligation of death receptors) and the intrinsic pathways (stimulated by intracellular stress causing mitochondrial membrane permeabilization). Furthermore, the consortium will comparatively asses the system biology of apoptotic and non-apoptotic cell death (necrosis, autophagy and mitotic catastrophe) in order to understand the extent of overlap in the mechanism leading to different phenotypic manifestation of cell death as well as the molecular ”switches” that decide whether cells remain alive or die through one or the other cell death pathway.

 

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no HEALTH-F4-2007-200767 for APO-SYS.