Project Details
Projekt
Modeling hepatic regeneration and four-scale test compound metabolism
Applicant
Dr. Lars Ole Schwen
Subject Area
General and Visceral Surgery
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 436883643
The goal of the research unit is to better predict the recovery of hepatic function during regeneration after liver surgery of diseased livers. Hepatic disease affect hepatic processes at different spatial scales: individual hepatocytes, hepatic sinusoids/lobuli (including zonated phenomena), the organ, and the entire organism. Surgery and subsequent regeneration further perturb the hepatic processes at the different scales. In QuaLiPerF, these effects will be included in computational models of the metabolization of selected test compounds representative for liver function.The goal of this project is to build a multi-scale computational model of test compound metabolism during liver regeneration. For this purpose, this project will integrate models at the cellular, lobular, and organism scale (by the modeling partners) with own models at the organ scale, in a four-scale framework. Combining the relevant complex and interacting processes in a computational model will require a deep understanding of the underlying physiology, biology, and biochemistry and of suitable modeling techniques for the respective spatial scales. Our mechanistically driven model translation and integration will be complemented by a data-driven approach in collaboration with the data integration partner. The computational models to be developed will be parameterized and validated using clinical and experimental physiological and metabolic data. In addition, this project will combine the data acquired during regeneration to descriptive computational model of the recovery of physiological and metabolic parameters over time, to be combined with the models of test compound metabolization. Predictions obtained from simulations using the computational models will be used in QuaLiPerF to investigate biological and clinical questions driven by the clinical and experimental partners. Ultimately, a better prediction of the recovery of liver function developed in QuaLiPerF will help improve planning of individual surgery.
DFG Programme
Research Units
