Summary
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.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/948170 |
| Start date: | 01-02-2021 |
| End date: | 31-01-2026 |
| Total budget - Public funding: | 1 499 988,00 Euro - 1 499 988,00 Euro |
Cordis data
Original description
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.Status
SIGNEDCall topic
ERC-2020-STGUpdate Date
27-04-2024
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