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Dissecting the (epi)genetic origins of phenotypic variation and metabolic disease susceptibility

Objective

Current estimates place the prevalence of obesity beyond 1 billion by the year 2030. As a critical risk factor for heart disease, diabetes and stroke, obesity represents one of the chief socio-economic challenges of our day. While studies have mapped a genetic framework for understanding obesity, the etiological contribution of several regulatory layers, and in particular epigenetic regulation, remain poorly understood. A perfect example, we know that isogenic C57Bl6/J mice can vary by as much as 100% in body weight upon high fat feeding; currently, we have no mechanistic explanation for the emergence of such phenotypic variation. Here, I propose three aims dedicated towards understanding the (epi)genetic control of phenotypic variation and disease susceptibility. First, we will catalogue epigenome and phenome variation to an unprecedented depth and resolution in the isogenic context. Next, we will examine two completely novel models of epigenetically sensitized bi-stable obesity and thus begin a mechanistic dissection of phenotypic variation. Finally, we will map a series of gene-gene and gene-environment epistasis interactions including eight models of developmental plasticity and approximately a dozen chromatin regulator mutants. The latter epistasis matrix will identify the molecular mechanisms that trigger, amplify and buffer phenotypic variation and stochastic obesity in mice. The functional (epi)phenomics approach is unique. It builds the first unbiased framework against which to understand developmental plasticity and phenotypic variation, and at the same time generates powerful resources for disease researchers worldwide.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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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.

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.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2015-CoG

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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

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.

€ 1 997 853,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

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.

€ 1 997 853,00

Beneficiaries (1)

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