Objective
Epigenetic pathways contribute to cancer development and progression. These pathways act via proteins that modulate chromatin structure and gene expression, and can thereby give pro-proliferative and anti-apoptotic properties selected for in cancer. In total ~400 factors are known that either modify chromatin directly as epigenetic ‘writers’ (DNA methyltranserases, histone methyltransferases, acetyltransferases, kinases, ubiquitinases) and ‘erasers’ (histone demethylases, deacetylases, phosphatases, deubiquitinases) or indirectly by moving nucleosomes (‘remodelers’) or binding to the modifications set by the ‘writers’ (‘readers’; e.g. bromo, PHD, chromo, tudor domains). Small molecules inhibiting several chromatin modifying enzymes have been developed, and HDAC inhibitors and DNA methyltransferase inhibitors are approved drugs. While DNA methyltransferases and histone deacetylases are well-established drug-targets, the majority of the ~400 chromatin modifiers is not studied in cancer. Furthermore, the functional link between genetic alterations of the genes encoding these enzymes and increased proliferation in a cancerous state is less well established.
Here we propose to generate and apply tools to systematically study these proteins in cancer using epigenome-wide knock-down studies and small molecule probes. This project directly benefits from the experience at the Broad Institute, where Stefan Kubicek worked for 3.5 years, which allowed him to bring to CeMM a library of knock-down constructs targeting all chromatin proteins in collaboration with the Broad RNAi platform. Similarly, his work on histone demethylases has yielded interesting probe compounds, and his continuing collaboration is recognized by his continuing status as a Remote Associate Researcher of the Broad Institute Chemical Biology Program. Stefan Kubicek started at CeMM in August 2010 and funding of this EPICAL proposal will allow to further integrate his career in the European research space.
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
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2011-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
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.