Objective
Acute promyelocytic leukemia (APL) appears to be primarily a monogenic disease characterised by a specific t(15 ;17) translocation that fuses the PML and the RARA gene to generate a PML/RAR fusion protein. PML/RARA is a transcriptional repressor, and RARA homo-dimerisation through the coiled coil of PML was believed to be the basis for repression via enhanced binding of co-repressors. Clinically, APL is exquisitely sensitive to retinoic acid (RA), arsenic trioxide and cAMP. This cardinal feature of the disease has been used to model its pathogenesis by analyzing the response to therapy of primary cells in vivo and ex vivo.
Our aim is a further understanding the pathogenesis of acute promyelocytic leukemia, in particular the molecular bases of its response to RA, arsenic and cAMP. This will be essentially achieved through the analysis of the phenotype and transcriptome of cells or animals expressing PML/RARA mutants, by applying innovative approaches in cellular and molecular biology, such as purification of tagged proteins and ChIP.
We propose two main objectives:
- Partners identification of the oncogenic PML/RARA complex. Subsequently, we will analyse the functional domains of the complex and the changes in the complex induced by RA, arsenic and cAMP.
- Analysis of PML/RARA-dependent target gene repression. We will compare between different PML/RARA mutants in respect to the chromatin or DNA status of the target gene promoters.
This project addresses new therapeutic targets in APL and other types of cancer where RARA is implicated. It is a multidisciplinary project that involves a highly valuable education for the candidate in new scientific aspects related to her research field.
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 biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences molecular biology
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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-2009-IEF
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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.
Coordinator
F-75205 / 13 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.