Project description
The role of cardiomyocyte receptors in myocardial infarction
The EU-funded R-FunSel project is working to identify novel therapeutic targets for myocardial infarction (MI), the leading cause of heart failure. Scientists are using the CRISPR/Cas9 genome editing technology to perform in vivo systematic screening of cardiomyocyte receptors. For this purpose, they will use a mouse model of MI and identify genes necessary for cardiomyocyte survival, cardioprotective genes as well as genes that code for detrimental factors. The proposed approach offers an unbiased way to shed light on the mechanisms of MI, contributing to the translation of basic research into novel therapeutic targets.
Objective
Myocardial Infarction (MI) is the leading cause of heart failure, which represents a major medical, social and economic burden worldwide. There is a desperate need for new therapies for these conditions. Here we propose a new approach for the in vivo, unbiased and systematic identification of receptors involved in MI, which might become targets for innovative therapeutics. The method we developed, named Reverse Functional Selection (R-FunSel) takes advantage of the CRISPR/Cas9 genome editing technology and is based on the intracardiac screening of a library of single-guide (sg) RNAs in Cas9 transgenic mice upon gene delivery using the highly cardiotropic adeno-associated virus serotype 9 (AAV9). First, we will construct an arrayed library of sgRNAs, individually cloned into AAV9 vectors, driving CRISPR/Cas9 towards each of the receptor genes expressed by cardiomyocytes. Second, we will package pools of this library and transduce the mouse heart, at a multiplicity by which each vector enters a different cell. Then, MI will be applied as a selective stimulus and, after a few weeks, vector inserts will be recovered from the viable tissue and their frequency measured by Next Generation Sequencing. R-FunSel is based on Darwinian selection of cardiomyocyte survival, thus sgRNAs that will be lost are likely to target cardioprotective genes while those that are enriched code for detrimental factors. The choice to develop R-FunSel for the systematic screening of cardiomyocyte receptors will allow identification of novel druggable targets for the development of therapeutics, either in the form of molecules activating the protective receptors or inhibiting them or their ligands. R-FunSel is based on solid technologies that support the feasibility and power of the in vivo screening approach. Compared to biochemical or phenotypic studies, screening in vivo directly for function is a novel strategy to move basic research into translational medicine at a quick pace.
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 medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics RNA
- medical and health sciences clinical medicine cardiology
- natural sciences biological sciences genetics genomes
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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-2018
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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.
WC2R 2LS London
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.