The aim of this project is the development of mathematical models integrating metabolic and signaling pathways.
From our VLN partner groups, we require the following experimental and theoretical input:
- Sub-models (Boolean or kinetic) of signaling pathways in hepatocytes
- Protein level and phosphorylation status of key protein kinases and phosphatases involved in the signaling pathways of insuline, HGF, TGF-ß, Wnt
- Measured metabolite concentrations and metabolic flux rates at various external hormonal stimuli
- Gene expression profiling of metabolic enzymes at various external hormonal stimuli
Method:
- Development of hybrid models (kinetic model and/or FBA model of metabolic part/discrete state model of regulatory part)
Milestones:
- Development and testing of methods to combine FBA models of metabolic pathways and Boolean models of signaling pathways
- Including knowledge (data, Boolean models) on signaling pathways of insulin, glucagon, TGFß and HGF into integrative model of hepatocyte
This project is part of Virtual Liver, a major national initiative funded by the German Federal Ministry for Education and Research (BMBF) and is connected to WP subprojects A3.1, E1, and E4.
Researchers
Prof. Hermann-Georg Holzhütter
Sascha Bullik
(Christian Bölling)