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

Acronym	DYNAFLOW (Reference Number: JTC1_22)
Duration	01/05/2016 - 01/03/2020
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 willeventually require liver transplantation. Following a primary immunological insult, biliary flow obstruction leads to pressure damage to thebiliary 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. Wewill:i) experimentally map and model the 3D structure and cellular interactions of small bile ducts in well characterized and long-term followedpatients 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 andv) 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 neededpharmacological intervention to prevent biliary pressure damage and B) pave the way for personalized pharmacological biliary pressureoptimization in affected patients.Expertise & Consortium: Intriguingly, biliary flow dynamics, pressure sensing and the signalling consequences are as yet very poorlyunderstood. Thus, the consortium unites established liver research with mechanosensing and modelling expertise that has never beensystematically applied in a PSC context. Specifically, the consortium unites renowned liver research centres from Norway (clinical PSC) andAustria (experimental PSC) with fluid dynamics (Israel), high-definition 3D tissue reconstruction, functional genomics (Germany) andmechanosensing (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