Project: Dynamic bile flow modelling and cellular sensing in primary sclerosing cholangitis

Acronym DYNAFLOW (Reference Number: JTC1_22)
Duration 01/05/2016 - 30/04/2019
Project Topic Medical need: Primary sclerosing cholangitis (PSC) is a progressive liver disease characterized by fibroobliterative destruction of the intraand/ or extra-hepatic bile ducts, leading to liver cirrhosis. There is no effective medical therapy for PSC, and the majority of patients will eventually require liver transplantation. Following a primary immunological insult, biliary flow obstruction leads to pressure damage to the biliary epithelium and hepatocytes and drives disease progression. Approach: We will use a systems biology approach to model the hydrodynamic and signalling consequences of the altered biliary flow. We will: i) experimentally map and model the 3D structure and cellular interactions of small bile ducts in well characterized and long-term followed patients and animal models of PSC, ii) perform 3D geometry-based hydrodynamic modelling, iii) calibrate models on intravital imaging of biliary flow in murine models, iv) look at the consequences on cellular programing using in-situ functional genomics and v) mechanistically analyse and model biliary pressure sensing and it´s signalling consequences. Yield: The resulting spatiotemporal model of altered bile flow and signalling will allow A) to identify targets for the utterly needed pharmacological intervention to prevent biliary pressure damage and B) pave the way for personalized pharmacological biliary pressure optimization in affected patients. Expertise & Consortium: Intriguingly, biliary flow dynamics, pressure sensing and the signalling consequences are as yet very poorly understood. Thus, the consortium unites established liver research with mechanosensing and modelling expertise that has never been systematically applied in a PSC context. Specifically, the consortium unites renowned liver research centres from Norway (clinical PSC) and Austria (experimental PSC) with fluid dynamics (Israel), high-definition 3D tissue reconstruction, functional genomics (Germany) and mechanosensing (France).
Network ERAcoSysMed
Call 1st Call: European Research Projects to demonstrate the feasibility and benefits of systems medicine

Project partner

Number Name Role Country
1 Technical University Dresden Coordinator Germany
2 Oslo University Hospital / Rikshospitalet Partner Norway
3 Medical University of Vienna Partner Austria
4 Max-Planck-Institute for Cell Biology & Genetics Partner Germany
5 Israel Institute of Technology Partner Israel
6 CNRS AMU Partner France