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Chromatin & Splicing

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Cerrado

THE ROLE OF EPIGENETICS IN THE REGULATION OF CELL SPECIFIC ALTERNATIVE SPLICING...

THE ROLE OF EPIGENETICS IN THE REGULATION OF CELL SPECIFIC ALTERNATIVE SPLICING PROGRAMS 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, i... ver más

31/12/2017

CNRS

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2017-12-31 No tenemos la información de la convocatoria

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

CNRS

0.00€ | Lider

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Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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