Objective
Although multiple regulatory layers have been reported to control stem cell differentiation, including epigenetics, cell signaling and metabolism, we still lack sufficient knowledge on how differentiation processes are connected and coordinated. The Hentze laboratory recently discovered that RNA modulates (riboregulates) the activity of the glycolytic enzyme Enolase 1 (ENO1) and that this interaction is essential for in vitro murine embryonic stem cell differentiation. Additionally, unpublished data from the laboratory show that the glycolytic enzyme pyruvate kinase (PKM) is also riboregulated. However, the role of riboregulation during primary stem cell differentiation remains elusive. Previously, RNA-bound proteomes have either been identified in cultured cells or ex vivo in whole organs. I aim to investigate enzyme-RNA interactions in primary stem cells and differentiated progeny, using the hematopoietic system as a model. First, I will analyze the RNA-binding activity of previously in cellulo profiled enzymes ENO1 and PKM in vivo and ex vivo during hematopoietic stem cell (HSC) differentiation by RNA-proximity ligation assays, profiling of stem cell activity and transcriptome analysis (aim 1). Secondly, I will analyze, identify and comparatively quantify global RNA-protein interactions in HSCs, progenitors and mature blood cells by developing a method to profile in vivo RNA-protein interactions (aim 2). In an interdisciplinary approach, I will pair fluorescence-activated cell sorting with state-of-the-art RNA-protein cross-linking approaches and ultra-low input proteomics analysis. The generated data will help, for the first time, to understand at the analytical and functional level whether and to what degree riboregulation of enzymes represents a regulatory paradigm operational in mammalian cells, with a focus on hematopoietic stem cell differentiation.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences genetics epigenetics
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2022-PF-01
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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.
69117 Heidelberg
Germany
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.