Objective
Epigenetics research has revealed that in the cell’s nucleus all kinds of biomolecules–DNA, RNAs, proteins, protein posttranslational modifications–are highly compartmentalized to occupy distinct chromatin territories and genomic loci, thereby contributing to gene regulation and cell identity. In contrast, small molecules and cellular metabolites are generally considered to passively enter the nucleus from the cytoplasm and to lack distinct subnuclear localization. The CHROMABOLISM proposal challenges this assumption based on preliminary data generated in my laboratory. I hypothesize that chromatin-bound enzymes of central metabolism and subnuclear metabolite gradients contribute to gene regulation and cellular identity.
To address this hypothesis, we will first systematically profile chromatin-bound metabolic enzymes, chart nuclear metabolomes across representative leukemia cell lines, and develop tools to measure local metabolite concentrations at distinct genomic loci. In a second step, we will then develop and apply technology to perturb these nuclear metabolite patterns by forcing the export of metabolic enzymes for the nucleus, aberrantly recruiting these enzymes to selected genomic loci, and perturbing metabolite patterns by addition and depletion of metabolites. In all these conditions we will measure the impact of nuclear metabolism on chromatin structure and gene expression. Based on the data obtained, we will model for the effects of cellular metabolites on cancer cell identity and proliferation. In line with the recent discovery of oncometabolites and the clinical use of antimetabolites, we expect to predict chromatin-bound metabolic enzymes that can be exploited as druggable targets in oncology. In a final aim we will validate these targets in leukemia and develop chemical probes against them.
Successful completion of this project has the potential to transform our understanding of nuclear metabolism in control of gene expression and cellular identity.
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 biological sciences genetics RNA
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences genetics epigenetics
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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)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2017-COG
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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.
1090 Wien
Austria
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.