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)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
08003 Barcelona
Spain