Objective
Acute myeloid leukaemia (AML) is an aggressive type of blood cancer characterized by uncontrollable growth of immature myeloid cells. Somatic mutations in diverse transcriptional regulators result in aberrant epigenetic landscape in leukemic cells, including patterns of DNA methylation. Due to its reversible nature, this epigenetic mark has been a promising therapeutic target and DNA methyltransferase inhibitors are already being used with varying degrees of success in clinic. The targeted improvement of existing therapies requires a better understanding of mechanisms how altered DNA methylation promotes malignancies. TET2, an enzyme catalysing DNA demethylation, is one of the most frequently mutated epigenetic regulators in AML. Its loss leads to hypermethylation at distal regulatory regions (or enhancers) and increased stem cell self-renewal and leukaemogenesis in the haematopoietic system. In the proposed work I plan to investigate the link between aberrant hypermethylation at enhancers and its role in developing and maintaining AML. Firstly, I will take advantage of clinically relevant AML mouse models that combine TET2 deficiency with AML-specific alterations and annotate DNA methylation-sensitive enhancers using high-throughput sequencing methods (MethylC-seq, ATAC-seq and ChIP-seq). Secondly, I will perform a positive-selection CRISPR-based high-throughput enhancer screen to identify DNA methylation-sensitive enhancers that inhibit leukemic stem cell self-renewal (i.e. tumour suppressive regulatory regions). Finally, I will identify and study the function of transcription factors which binding is lost due to aberrant DNA hypermethylation at these sites. The proposed work will be both discovery-based (genome-wide level) as well as mechanistic.
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
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
You need to log in or register to use this function
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.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
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.
MSCA-IF-EF-ST - Standard EF
See all projects funded under this funding scheme
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) H2020-MSCA-IF-2016
See all projects funded under this callCoordinator
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.
1165 KOBENHAVN
Denmark
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.