Project description
tRNA signatures as novel markers of cancer stem cells
Cancer stem cells (CSC) represent a population of transformed cells that sustain tumour growth and are responsible for metastasis and drug resistance. The genetic heterogeneity of CSC prevents the discovery of markers uniquely expressed by these cells. Transfer RNAs (tRNAs) are adaptor RNA molecules that link the mRNA and the amino acid sequence of proteins. The EU-funded tRNAtoGO project is testing the idea that the expression of a specific signature of tRNA molecules promotes the expression of oncoproteins, sustaining CSC transformation. The identification of a tRNA-permissive signature might be a marker of the population of CSC. Researchers will use a combination of genetic CRISPR-Cas9-based screens, mouse models and functional assays to identify transformation-permissive tRNAs and their biological role.
Objective
Cells integrate internal and external stimuli by continuously adapting their transcription and translation. tRNAs are heterogeneous and highly modified molecules necessary to correctly translate mRNAs into proteins. Even though their discovery goes back to the late 50s, it is only in the last years that their active role in regulating translation has started to be highlighted both in health and disease. Cancer stem cells (CSC) are a small population of transformed cells able to sustain tumor growth and responsible for metastasis and drug resistance. The incredible plasticity and genetic heterogeneity of CSC make it extremely difficult to find global markers and/or molecular footprints uniquely expressed by these cells. In the tRNAtoGO project, I postulate that the expression of a specific signature of tRNA molecules permits the establishment of onco-proteomes therefore sustaining cancer stem cells transformation. Therefore, the identification of a tRNA permissive signature might be predictive of the population of origin of CSC. To prove this hypothesis, I will use a combination of unbiased sequencing approaches, a genetic CRISPR-Cas9 based screen, mouse models and functional assays that will identify, in the intestine, the Wnt-driven transformation permissive tRNAs and associated modification enzymes signature and their biological role. In conclusion, this project aims to tackle the CSC concept from a new and extremely innovative prospective: I want to describe the cellular origin of CSC as a population harboring a permissive-tRNA signature for driving mutations.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
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Funding Scheme
ERC-STG - Starting GrantHost institution
4000 Liege
Belgium