APO-SYS Consortium

 

Apoptosis Systems Biology Applied to Cancer and AIDS

 

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

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The APO-SYS Consortium

The APO-SYS team is the extension of a 2006 Descartes Prize-winning consortium  (“Apoptosis mechanisms in cancer and AIDS” led by Guido Kroemer) that involves the coordinator of the present consortium (Boris Zhivotovsky) as well as four additional participants (Marja Jäättelä, Mauro Piacentini, Josef Penninger and Klaus-Michael Debatin/Simone Fulda). This consortium has now been extended to a total of 23 partners with the aim of uniting a critical mass of investigators specialized in biology, biomedicine/translational medicine, bioinformatics, biomathematics and biostatistics that may solve important, disease-relevant problems by a systems biology approach of apoptosis and other cell death programs. Three of the partners involved in the theoretical part (Emmanuel Barillot, Ralf Herwig/Hans Lehrach, Ron Shamir) were previously involved in a common EC project on systems biology in FP6 ("European  Systems Biology Initiative for combating Complex Diseses") http://pybios.molgen.mpg.de/ESBIC-D), led by Hans Lehrach. Furthermore, the APO-SYS consortium involves a BioTech company that is specifically interested in systems biology approaches applied to apoptosis-relevant diseases.
 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 will address 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.

The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° HEALTH-F4-2007-200767 for APO-SYS.