Objective
The direct conversion approach and the generation of induced pluripotent stem cells (iPSCs) provide an invaluable resource of cells for disease modelling, drug screening, and patient-specific cell-based therapy. However, the directly converted cells are not stable, and the vast majority of iPSCs exhibit poor developmental potential as measured by stringent pluripotency tests. This suggests that the prevailing method of reprogramming is not ideal and leads to aberrant/incomplete conversion. To improve the quality of the converted cells, efforts should be focused on uncovering the molecular mechanisms that characterize the nuclear reprogramming process. There are two critical hurdles that hinder the progress of deciphering the elements that dictate successful reprogramming: (1) The ability to detect and capture solely the rare cells that eventually will be converted and (2) to monitor the transcriptional profile of cells at the single-cell level. Single-cell technology is in its infancy and many of the methods used today are characterized by high noise to signal ratio. In this grant proposal we intend to overcome these limitations by (1) establishing a complex fluorescent knock-in reporter system using the CRISPR/Cas9 method to capture the early rare reprogrammable cells and by (2) employing several cutting-edge single-cell technologies, RNA-Seq, Fluidigm BioMark and single-molecule mRNA-FISH, to segregate the real signal from the noise. To identify common and more global elements that facilitate nuclear reprogramming at large, we will trace in parallel, reprogrammable cells from two different somatic cell conversion models that reach high degree of nuclear reprogramming, and analyse their transcriptome using sophisticated bioinformatic tools. This study will provide a general overview of the changes that occur during the conversion of various cell types and will uncover the basic features that are essential to reach safe and complete conversion.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- natural sciences physical sciences optics microscopy
- social sciences sociology social issues social inequalities
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics RNA
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
ERC-STG - Starting Grant
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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) ERC-2015-STG
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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.
91904 JERUSALEM
Israel
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.