Investigating aspects of metabolism pertinent to atherosclerosis utilizing computational techniques.

ended

Cardiovascular disease (CVD) claims 17.9 million lives and costs the European economy €210 billion annually. New, innovative strategies are needed to address this health crisis. IMPACT takes a systems medicine approach to extend our understanding of the factors that contribute to cholesterol metabolism and to develop innovative therapeutic approaches for atherosclerotic cardiovascular disease (ACVD). IMPACT has three objectives: 1) Develop an LP algorithm that analyzes models of human and microbiome metabolism to identify optimal microbes and nutrients that may influence metabolic pathways of interest. 2) Develop a detailed model of cholesterol metabolism, that is trained and validated using human data, by synergistically merging FBA models with an ordinary differential equation (ODE) model of cholesterol transport. Simulations and statistical analysis on the in-silico results will be conducted to identify metabolic pathways related to ACVD and to investigate how variables such as microbiome composition, sex, obesity, and diet influence cholesterol metabolism and ACVD risk. 3) Metabolic pathways related to ACVD risk will be targeted by the LP algorithm to identify optimal microbial and nutritional therapies that can treat and/or diminish the progression of ACVD. Promising bacterial strains and nutrients will be tested with in-vivo gut simulators in an intersectoral secondment with International Flavors & Fragrances Inc. Results of the proposed research will be effectively disseminated and exploited to maximize IMPACT. While the action serves to extend the state-of-the-art and address a health crisis, IMPACT will simultaneously expand my technical knowledge and transferable skills, bolster my credentials and enhance my career competitiveness through intersectoral exposure.