[tRansGlio] Investigating the role of tRNA-dependent translational control in the onset and progression of Glioblastoma.
Ente: EC
Scadenza: 2029-08-31
Importo max: 226.421 EUR
Paese: EU
Descrizione
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.
Settori: Horizon Europe Topics
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