Project description
Decoding tRNA-mediated translational control in glioblastoma
Glioblastoma multiforme is a highly aggressive form of brain cancer that is difficult to treat. Supported by the Marie Skłodowska-Curie Actions programme, the tRansGlio project explores how transfer RNA (tRNA)-mediated translational control influences gene expression in paediatric and adult glioblastoma. It will use tRNA sequencing and ribosome profiling to map tRNA landscapes, quantify translational efficiency at codon resolution, and compare paediatric and adult samples. The project will also investigate the functional role of tRNAs in tumour initiation, growth and response to therapy. Overall, the findings may pave the way for new diagnostic approaches and targeted treatments for brain cancer.
Objective
Glioblastoma (GB) is a highly lethal brain cancer. Recent studies revealed striking differences between paediatric and adult GB tumours. Notably, the cellular hierarchy of GB mirrors lineage trajectories in the developing brain, supporting the view that GB originates from the malignant transformation of Neural Stem Cells (NSCs) into Glioblastoma Stem Cells (GSCs).
Regulation of translation, via the availability of the key adaptors, transfer RNAs (tRNA), represents a sophisticated yet underestimated mechanism to regulate gene-expression.
Although emerging evidence indicates that translational programs and tRNAs are impaired in adult GB, it remains largely unknown (i) how tRNA pools are altered in GB; and (ii) how GB exploits tRNA availability to meet its translational demands and reprogram its proteome.
My main goal is to demonstrate how GB leverages tRNAs-mediated translational control to drive tumour initiation, progression, and resistance to therapy, in paediatric and adult GB.
To test it, I will (i) map the tRNAs landscapes using a state-of-the-art tRNA-seq method; (ii) define mRNA/codon translational efficiency by Ribo-seq, in paediatric and adult GB samples (i & ii); and (iii) assess the causative role of tRNAs in NSCs transformation, GSCs proliferation and sensitivity to chemotherapeutic agents, by manipulating tRNAs levels in NSC/GSC lines.
Overall, with this MSCA I will provide unprecedented high-resolution characterisation of tRNA pools in GB, with the potential to refine diagnostic and prognostic tools, opening also new and biomedical career opportunities for me. I will also define how key GB translational programs are shaped by tRNAs availability and cause tumour onset or progression. Ultimately, our work could pave the way for novel, more effective drugs, targeting tRNAs or tRNA biogenesis factors, which could extend GB patients’ survival in the future. Our approach may also help to address unmet clinical needs in the broader cancer field.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine oncology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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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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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-2025-PF
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75654 Paris
France
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