Objective
One of the most critical epigenetic and chromatin remodelling processes in mammalian development occurs shortly after fertilization restoring totipotency. Due to limited cell numbers and lack of experimentally tractable systems, the mechanisms and regulation of this developmental stage are poorly understood. This proposal will provide important mechanistic insights into the epigenetic control of early embryonic gene expression, and its relevance to somatic reprogramming.
Murine embryonic stem cells (ESCs) contain a rare sub-population of early embryonic like (EEL) cells expressing genes normally restricted to the pre-implantation embryo, with enhanced extra-embryonic differentiation capability. Firstly, using novel single-cell technologies, I will characterize the EEL cells in detail, validating them as an in vitro model of pre-implantation development. On-going research in the host lab that I am involved in has identified an epigenetic enhancer that expands this EEL sub-population. Through bioinformatic analysis of pre-implantation transcriptome data, I have shortlisted 34 epigenetic and chromatin-associated proteins, including the previously identified factor, which will be systematically screened to identify new enhancers of totipotency. Validated EEL regulators, including two additional newly confirmed factors, will be analysed mechanistically determining their interaction partners, interdependencies, and mode of action. Finally, the contribution of the totipotency regulators towards the efficiency and fidelity of somatic reprogramming will be determined, potentially improving the use of this technology for personalised gene therapy and regenerative medicine.
This state-of-the-art proposal uses innovative and novel cutting-edge technologies and combines the expertise of the researcher and the host. It has the potential for significant impact across several fields from epigenetics and stem cell biology to reprogramming and regenerative medicine.
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.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences developmental biology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine embryology
- natural sciences biological sciences genetics epigenetics
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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-2014
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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.
CB22 3AT 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.