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Reprogramming cell identity to develop new therapies against Cholangiopathies

Objective

Intra- hepatic Cholangiocytes represent one of the main cell type of the liver with hepatocytes. They line the biliary tract and fulfill essential functions such as bile modification and transport. Cholangiocytes are targeted by a diversity of diseases including genetic disorders such as Cystic Fibrosis. There is currently no cure for disorders affecting cholangiocytes and end stage disease require liver transplantation. Importantly, primary cholangiocytes obtained from biopsy can not be grown in vitro without loosing their functional characteristics while transformed cells and animal models rarely recapitulate the entire pathophysiology of human diseases. Consequently, the development of novel drug and therapies remains problematic despite an urgent clinical need. Human induced pluripotent stem cells could provide an advantageous solution to bypass this major challenge. Indeed, these pluripotent stem cells are generated by direct reprograming of somatic cells and they can proliferate almost indefinitely in vitro while maintaining their capacity to differentiate into almost any cell types. Interestingly, hIPSC can be derived from patients with genetic disorders and then differentiated into the relevant cell types for disease modeling purposes. Of direct interest, we recently developed a protocol to generate cholangiocytes from hIPSCs using chemically define conditions. The resulting cells display functional characteristics of their in vivo counterpart including the capacity to transport bile acid. Here, we propose to enable our culture system for the production of large quantity of hIPSCs derived cholangiocytes in conditions compatible with the pharmaceutical industry requirements. The resulting cells will be then fully characterized to validate their relevance for modeling Cystic fibrosis and for testing small molecules. Thus, the overall objective of this project is to create a novel drug screening platform for the discovery of therapeutics targeting genetic form of cholangiopathies.

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-POC - Proof of Concept Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2015-PoC

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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 149 907,00
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 149 907,00

Beneficiaries (1)

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