A systems biology approach to RESOLVE the molecular pathology of two hallmarks of patients with metabolic syndrome and its co-morbidities; hypertriglyceridemia and low HDL-cholesterol
A collaborative project funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 305707, research area FP7-HEALTH-2012-INNOVATION-1, topic HEALTH.2012.2.1.2-2: Systems medicine: Applying systems biology approaches for understanding multifactorial human diseases and their comorbidities
Through combining basic pre-clinical and clinical research, network analysis and computational modelling, RESOLVE aims at resolving the disturbed dynamics and mechanisms underlying the high triglyceride (HTG) and low high-density lipoprotein cholesterol (HDL-C) phenotype and insulin resistance in patients with metabolic syndrome (MetS) and its associated co-morbidities (cardiovascular disease, CVD; type 2 diabetes, T2DM; non-alcoholic fatty liver disease, NAFLD). RESOLVE will deliver on 6 specific objectives:
- build a computational model for analyzing the kinetics of plasma lipids, lipoproteins and their interactions with glucose metabolism;
- apply the iterative systems biology cycle for calibrating, validating and improving the computational model in dedicated studies in mice;
- build, calibrate and validate the computational model for use in humans;
- analyze – based on model and experimental data – which processes in the murine metabolic network regulatethe physiological response to perturbations in lipid, lipoprotein and glucose metabolism and how these interact;
- analyze – based on model and experimental data – which processes in the human metabolic network regulatethe physiological response to perturbations in lipid, lipoprotein and glucose metabolism and how these interact;
- use the human model to identify network-based drug targets aimed at restoring the metabolic dyslipidemia and glycemic control in patients with MetS and associated comorbidities.
The 60-months project RESOLVE will result into a novel strategy for development of therapeutic strategies for MetS patients with T2DM, NAFLD or CVD.
GeneXplain’s role is to contribute to the general IT infrastructure of the project, to use the company’s technology platform for providing a database of the project-specific data, and to help with training courses for the data management.