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.