Project description
Chromatin regulation in haematopoiesis
Chromatin factors (CFs) drive cellular fate and developmental lineage decision by participating in dynamic chromatin complexes and regulating gene expression. Given that CFs are among the most frequently mutated proteins in various blood malignancies, as for example in mixed lineage leukemia (MLL), the EU-funded ChRONAM-H project set out to determine the role of these proteins in haematopoietic lineage commitment. Through state-of-the-art chromatin profiling technologies, scientists will link CFs with transcription factors in both normal and malignant haematopoiesis. Results will provide fundamental information on genome regulatory mechanisms and also identify molecular targets to fight leukemia.
Objective
Chromatin Factors (CFs) comprise a diverse family of proteins that elicit key regulatory epigenetic activities during the regulation of cellular fates. Although this heterogeneous group has been traditionally considered a static toolkit of epigenetic enzymes deployed to lineage-specific loci under the control of Transcription Factors (TFs), recent works have shown that CFs are crucial determinants of developmental lineage decisions that assemble into dynamic chromatin regulatory complexes with exquisite cell-type-specific composition. Hematopoiesis is a key developmental process largely dependent on Chromatin Factors. Importantly, CFs are the most recurrently mutated protein category across diverse blood malignancies. In fact, alterations in some of these proteins, like MLL fusions, have been proven to be central drivers of malignant transformation. However, in spite of this proven relevance, the contribution of most Chromatin Factors to blood lineage commitment remains largely unexplored; moreover, even for well-studied complexes such as SWI/SNF Polycomb or COMPASS, very little is known about the mechanisms that govern their locus-specific assembly and activity during cell fate specification.
My project Chromatin Regulation Of Normal And Malignant Haematopoiesis (ChRONAM-H) proposes a multidisciplinary framework to explore the functions of CFs during hematopoietic lineage commitment and malignant transformation. I will combine high-throughput functional measurements with state-of-the-art chromatin profiling technologies to unveil the lineage specifying roles of a large number of CFs and orthogonally link them within existing TF-centric networks in both normal and malignant hematopoiesis. This will shed light on the molecular behavior of chromatin regulatory complexes, providing new insights about the genome regulatory mechanisms that orchestrate hematopoiesis and how they might be therapeutically targeted to fight leukemia.
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 epigenetics epigenomes
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2019
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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.
CB2 1TN CAMBRIDGE
United Kingdom
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.