Objective
Maintaining a stable karyotype is essential for the use of pluripotent stem cells (PSCs) in regenerative medicine and translational and basic research. Although around 10-30% of PSC lines present karyotypic abnormalities, the molecular mechanisms underlying this genomic instability are largely unknown. Centromeres, the chromosomal loci that drive chromosome segregation are central to mitotic fidelity. Maintenance of centromeres in somatic cells is tightly cell cycle coupled, as centromeric chromatin assembly is strictly dependent on G1 phase transition. PSCs have an atypical cell cycle structure with truncated gap phases and proliferate at unusually rapid rates. How this affects mitotic fidelity in general, centromere assembly in particular and consequently, genomic stability is an essential question in reprogramming biology. The aim of this multifaceted project is to determine the mechanisms regulating proper chromosome segregation during somatic cell reprogramming to induced PSCs (iPSCs). By combining fluorescent labelling techniques, high-end microscopy and genome-wide analysis, this project will determine the mechanisms of centromere assembly and inheritance in PSCs, the consequences of genome-wide remodelling of chromatin marks during reprogramming on the stable epigenetic propagation of centromeric chromatin and how functional modulation of key centromere assembly factors affect mitotic fidelity. This project capitalises on the unique combination of the researcher’s experience in stem cell biology and iPSC technology and the extensive expertise in the biology of human mitosis and centromere function of the host lab. The results of this study will provide direct insight into how chromosomal segregation is controlled in PSCs and most importantly during reprogramming, which will advance our understanding of the mechanisms underlying the genomic instability of these cells and contribute to the development of strategies to obtain better and more robust iPSCs.
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 cell biology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
- medical and health sciences clinical medicine embryology
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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.
1067-001 LISBOA
Portugal
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.