Objective
Re-differentiation of carcinogenic epithelial cells to mesenchymal by epithelial-to-mesenchymal transition (EMT) confers properties to tumour cells, which turn them highly metastatic and resistant to chemotherapy. Traditionally, it was thought that expression of key genes was enough to induce EMT. However, very recently, alternative processing of transcribed genes into different matured mRNAs, and therefore proteins, by alternative splicing has also been implicated in EMT progression. Even more, switches in cancer-specific splicing isoforms to normal variants have been shown to reduce tumorigenicity and revert EMT. In parallel, recent observations point to an important regulatory role of chromatin structure and ncRNAs in modulating alternative splicing. This project aims to combine these new concepts to uncover, for the first time, the role of epigenetics in the regulation of cell-specific splicing programs in an inducible, physiologically relevant EMT cell reprogramming system. I will, first, probe at a gene-specific and genome-wide level the role of DNA and histone modifications in the establishment and maintenance of a new EMT-induced splicing program. Then, using a high-throughput screening approach, I will identify and characterize novel miRNAs and chromatin-based regulators of EMT-mediated alternative splicing that will be functionally tested for their capacity to impair EMT. This multidisciplinary project integrates novel concepts and challenging approaches in the field of epigenetics, ncRNA, splicing and cancer biology that will bring, conceptually and mechanistically, new insights into alternative splicing regulation and how cancer-specific splicing programs are established and maintained. In the long-term, this study has the potential to discover unexpected and innovative new molecular mechanisms of splicing regulation that can be applied for predicting and restoring cell-specific splicing patterns by mapping and modulating epigenetic modifications.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- 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.
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
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.
FP7-PEOPLE-2012-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
75794 Paris
France
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.