Objective
Substantial evidence indicates that even when genetically matched, we are not created equal. The mechanisms underlying such non-Mendelian phenotype variation are sufficient to elicit complex disease but remain unknown.
In this context, the regulators of chromatin state have the ability to establish cellular memory, which is encoding specific silenced gene expression states through mitosis and is involved in control phenotypic variation.
Interestingly, two chromatin ‘stabilizing’ genes (Trim28 / Dnmt3a) and two obesity buffering ‘effector’ genes (Peg3 / Nnat) are involved in triggering bi-stable epigenetic obesity.
This present proposal aims at intersecting all four models of polyphenism to identify the core transcriptional and chromatin machinery required to establish and switch ‘On’ or ‘Off’ the Obese state. Thus, I will to explore these four mutants [Trim28(D9/+), Dnmt3a(+/-), Peg3(+/-p), and Nnat(+/-p)], which will serve as a biological filter to reveal core requirements.
First, I will define co-variation of a spectrum of complex trait phenotypes resulting from insufficiency at each of these loci. Then, I will decipher the mechanism underlying their sensitized bi-stable obesity. Third, I will assess the epigenetic basis of their buffering of polyphenism.
The aim of this proposal is to precisely provide, for the first time, reference-depth phenomic and epigenomic profiling of chromatin sensitizer- (Trim28- / Dnmt3a-) and chromatin effector- (Peg3- / Nnat-) induced stochastic obesity. The work will uncover the first definitive genetic and genomic templates for probing non-Mendelian phenotypic variation and stochastic obesity and thus highlight new therapeutic perspectives.
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 clinical medicine endocrinology diabetes
- natural sciences chemical sciences analytical chemistry calorimetry
- medical and health sciences clinical medicine oncology
- medical and health sciences health sciences nutrition obesity
- 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-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.
80539 MUNCHEN
Germany
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.