Objective
Liver fibrosis (hepatitis B and C, cirrhosis, etc) represents an enormous health burden responsible for ~1.03 millions death per year worldwide according to the World Health Organization. Fibrosis is also a common outcome of many chronic diseases of the kidney (diabetic nephropathy), lungs (idiopathic pulmonary fibrosis), heart and vasculature (heart failure). In pathologies where fibrosis is a feature, there is an increased deposition of extracellular matrix proteins, including collagens that dramatically limit tissue function. Herein we propose to develop a cell-based assay for high-throughput screening of new antifibrotic therapeutics, which will accelerate fibrosis drug development. Our approach consists in the metabolic incorporation of an alkene-tagged proline in the biosynthesis of collagen, followed by labelling with a fluorescent tetrazine. We recently published preliminary results that provide proof of principle for the use of proline derivatives equipped with reactive handles to tag and label collagen structures. However, this approach suffered from nonspecific reactions of the fluorescent probe with intracellular proteins. The level of selectivity conferred by the proposed inverse-electron-demand Diels-Alder reaction is key in enabling its use in cells. We will use hepatic stellate cells since these cells are responsible for excess collagen production during liver fibrosis. To demonstrate that the cellular model can be used to screen compounds for fibrosis we will validate our system using a library of compounds with known preclinical antifibrotic activities. We will test if their in vivo efficacy can be predicted using cells. If our findings are significant we will use this cellular model to screen a commercial available library of compounds to find new antifibrotic drugs. The efficacy of the best candidate will be tested in vivo using two animal models of induced fibrosis.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences clinical medicine endocrinology diabetes diabetic nephropathy
- medical and health sciences basic medicine pathology
- medical and health sciences clinical medicine hepatology
- medical and health sciences clinical medicine cardiology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2015
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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.
CB2 1TN CAMBRIDGE
United Kingdom
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.