Project description
‘Specialised’ ribosomes and cell fate
Ribosomes are macromolecular structures consisting of RNA and protein that catalyse the synthesis of proteins. Once believed to be uniform, they are now known to display structural and functional diversity, including RNA modifications. This challenges previous theories and suggests that certain ribosomes are specialised ribosomes and can selectively translate specific messenger RNAs in processes such as cell differentiation. With the support of the Marie Skłodowska-Curie Actions programme, the NANORIBS project intends to study the role of RNA modifications in ribosome specialisation. To achieve this, researchers will employ a novel nanopore-based technique that maintains key ribosome features while enabling single-molecule resolution. The study will concentrate on how ribosomal modifications influence neuronal fate decisions, providing important insights into neurodegeneration.
Objective
Ribosomes, once considered uniform molecular entities, are now recognized for their compositional heterogeneity, challenging traditional views on their role in gene expression. This has led to the hypothesis of 'specialised' ribosomes that selectively translate specific mRNA subsets, though the extent of this specialisation, particularly in cell fate determination, remains debated. Recent findings suggest that rRNA modifications, such as 2’-O methylation, may drive ribosomal specialisation during cellular differentiation. However, how these modifications translate into specialised functions is still poorly understood. Current methods like ribosome profiling (RiboSeq) offer limited resolution, particularly at the isoform level and in untranslated regions (UTRs), limiting our ability to fully elucidate ribosome specialisation.
To address this, I propose NANORIBS, a novel nanopore-based ribosome profiling technique that achieves single-molecule resolution of ribosome footprints on full-length mRNAs. This method leverages long-read sequencing to preserve critical information such as poly-A tail length and UTR sequences, essential for understanding ribosome-mRNA interactions. NANORIBS will investigate the role of specific rRNA methylations, particularly the 18S:355Um modification, in neuronal cell fate commitment.
By offering unprecedented insights into the molecular mechanisms governing ribosome-mediated translation regulation during differentiation, NANORIBS could revolutionise our understanding of gene expression control at the translational level. Deciphering the functional consequences of rRNA modifications could lead to new therapeutic targets and strategies for diseases linked to aberrant cell differentiation, such as cancer and neurodegenerative disorders. NANORIBS not only advances ribosome biology but also paves the way for future research into the broader implications of ribosomal specialisation in health and disease.
Fields of science (EuroSciVoc)
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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.
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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)
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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
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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
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(opens in new window) HORIZON-MSCA-2024-PF-01
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08003 Barcelona
Spain
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