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Sergio RossellSergio Rossell, CSBB Post-doc since November 2010 Work Package 1, iterative modelling, prediction, and data integration of energy metabolism in AL2: Deriving a tissue-specific model of the human and mouse muscle metabolism to predict the effect of mutant phenotypes, the possible adaptations, and the effect of interventions. This project will exploit the extensive knowledge about human metabolism by modelling the energy metabolism’s known components and their pathway relationships. The formalization of this knowledge in a stoichiometric network holds >50 years of legacy data consisting of 3742 reactions (16% of which mitochondrial), 1905 genes and 2766 metabolites Computational analyses are becoming opportune because we have already identified the vast majority of the proteins present in the mitochondrion (>75%). We and others have shown the applicability of genome-scale stoichiometric models to unicellular organisms and it is only one step up to apply this same technique to human and mouse mitochondria. We will extend existing models of the complete human and mouse metabolisms with recently elucidated pathways5. The large size of such a stoichiometric model results in a huge space of possible flux distributions. To reduce this solution space and to derive a muscle-specific model for mitochondria, we will use multi-objective constrained optimization: i) by constraining the model with experimental data about gene expression and the presence of proteins and metabolites ii) by predicting disease-related cellular adaptations linked to the multiple objectives of mitochondrial function, like ATP production, assembly of FeS clusters and the expression of mitochondrially encoded genes; iii) by experimentally determining those fluxes that will give the strongest reduction in flux distribution space. Sergio Rossell is interested in the development of methodologies that combine experimental and theoretical elements, aimed at the elucidation of the relations between the properties of the constituent parts of biological networks and the system properties that emerge from the interaction of these parts. Short CV: Contact details: | ||
