Objective
Differentiation and acquisition of cell identity are fundamental processes in multi-cellular organisms. It is well established that chromatin and RNA mechanisms regulate cell fate determination. Mounting evidence from our lab and others, however, suggests that translation is an additional, until now underappreciated, determinant of cell fate. The importance of translation to differentiation can be gleaned from the hematopoietic system, where a prominent feature of human congenital syndromes, due to mutated ribosomes, is aberrant blood production. Crucially, these mutations lead to distinct cell-type-specific differentiation defects, rather than systemic failure. It remains unclear how congenital (total-body) ribosomal mutations only affect particular differentiation paths and manifest in a cell-type-specific fashion. We hypothesize that cell-type-specific ribosomal compositioni.e. ribosome heterogeneityresults in cell-type-specific translation profiles, and therefore represents a crucial layer of gene regulation in cell-fate and differentiation. We will explore this hypothesis by pursuing three complementary objectives: (1) Systematically map ribosome heterogeneity and reveal its function in normal hematopoiesis and leukemia; (2) Determine how ribosome heterogeneity controls cell-type-specific translatomes and contributes to cellular transformation; and (3) Explore ribosome heterogeneity at single-cell resolution, using novel methodologies we will develop for simultaneous transcription and translatome interrogation. By combining cutting-edge sequencing techniques with extensive genetic manipulations in physiological settings, we will reveal cell-type-specific translation, controlled by cell-type-specific ribosomes, as major regulators of cell fate in health and disease. Understanding the mechanisms of cell-type-specific translation will provide a new paradigm for elucidating gene expression regulation and for revealing new mechanisms for human diseases.
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 mutation
- medical and health sciences clinical medicine oncology leukemia
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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.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
HORIZON-ERC - HORIZON ERC Grants
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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) ERC-2022-STG
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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.
91904 JERUSALEM
Israel
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.