Developing predictive dynamic models of complex intracellular networks for neurological disease

Introduction: VALAPODYN, a European Commission funded research network, is an original systems biology approach for the development of an innovative model on the dynamics of molecular interaction networks (MIN) in relation to cell death and survival for the detection of new therapeutic targets for human neurological diseases. To this end, a comprehensive multidisciplinary strategy has been established combining functional genomics, proteomics and bioinformatics. Methods and Results: Using a mouse model of induced hippocampal sclerosis associated with focal epilepsy, dynamic expression analyses are conducted at different time points. Proteomic databases are being used along with advanced microarray and proteomics platform systems to investigate protein-protein interactions and regulation networks, identify and validate biological targets in complex intracellular pathways. The first phase involves whole genome and proteome analysis, integrating biological and statistical data in order to functionally annotate genes and proteins. Using Affymetrix microarrays, 2D-DIGE and MALDI/TOF-TOF, we are evaluating whole genome and proteome expression profiles bringing to light critical new pathways and molecular targets implicated in neurodegeneration. Discussion: VALAPODYN develops a dynamic and quantitative analysis method for new therapeutic targets through MIN dynamic models and specifically addresses the systems biology of complex cellular pathways and transcriptional networks. Novel predictive dynamic models will be validated by testing the selected drug targets on innovative in vivo and in vitro models of CNS pathologies. VALAPODYN will provide a cutting-edge highly accurate in silico tool for identifying novel and effective therapeutic targets in a faster, more efficient and more economical way than it is possible today