Summary
Cytotoxic CD8+ T-lymphocytes (CTLs) recognize and kill infected and malignant cells. Although CTLs recognize tumour-specific antigens, they often fail to limit cancer growth, as the cancer micro-environment rapidly suppresses their functionality. Therefore, there is the need to unveil new molecular circuits controlling CTL activation, the process through which T-cells proliferate and differentiate into an antigen-specific subpopulation with effector functions. In this way it will be possible to enhance CTL tumour-fighting capacity and improve the efficacy of immunotherapies, especially against solid cancers. My project will focus on how post-transcriptional regulation of metabolism modulates CTL activation. Post-transcriptional responses are fast and important for adaptation to rapidly changing environments. RNA-binding proteins (RBPs) are fundamental modulators of post-transcriptional regulation of many cellular processes, but less is known about how they regulate metabolism. By combining multi-omics approaches (i.e. proteomics, transcriptomics, metabolomics and in-vivo experiments) I will investigate how metabolic pathways in CTLs are modulated by specific RBPs. I will study how these RBPs regulate the stability and the translation of mRNAs encoding metabolic enzymes. Finally, I will control the expression of these RBPs in CAR-T cells (engineered T-lymphocytes used in cancer immunotherapies) to regulate metabolic pathways and enhance the in-vivo solid tumour-fighting capacity of these cells. Thus, my research will lay the groundwork for the identification of new methods to stimulate metabolism of tumour-infiltrating CTLs to enhance their functionality. My expertise in RNA-biology will complement the new skills I will learn from my host lab and collaborators, combining diverse disciplines to investigate fundamental immunological questions and apply my findings to in-vivo cancer immunotherapy.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101022265 |
| Start date: | 01-03-2023 |
| End date: | 28-02-2025 |
| Total budget - Public funding: | 212 933,76 Euro - 212 933,00 Euro |
Cordis data
Original description
Cytotoxic CD8+ T-lymphocytes (CTLs) recognize and kill infected and malignant cells. Although CTLs recognize tumour-specific antigens, they often fail to limit cancer growth, as the cancer micro-environment rapidly suppresses their functionality. Therefore, there is the need to unveil new molecular circuits controlling CTL activation, the process through which T-cells proliferate and differentiate into an antigen-specific subpopulation with effector functions. In this way it will be possible to enhance CTL tumour-fighting capacity and improve the efficacy of immunotherapies, especially against solid cancers. My project will focus on how post-transcriptional regulation of metabolism modulates CTL activation. Post-transcriptional responses are fast and important for adaptation to rapidly changing environments. RNA-binding proteins (RBPs) are fundamental modulators of post-transcriptional regulation of many cellular processes, but less is known about how they regulate metabolism. By combining multi-omics approaches (i.e. proteomics, transcriptomics, metabolomics and in-vivo experiments) I will investigate how metabolic pathways in CTLs are modulated by specific RBPs. I will study how these RBPs regulate the stability and the translation of mRNAs encoding metabolic enzymes. Finally, I will control the expression of these RBPs in CAR-T cells (engineered T-lymphocytes used in cancer immunotherapies) to regulate metabolic pathways and enhance the in-vivo solid tumour-fighting capacity of these cells. Thus, my research will lay the groundwork for the identification of new methods to stimulate metabolism of tumour-infiltrating CTLs to enhance their functionality. My expertise in RNA-biology will complement the new skills I will learn from my host lab and collaborators, combining diverse disciplines to investigate fundamental immunological questions and apply my findings to in-vivo cancer immunotherapy.Status
SIGNEDCall topic
MSCA-IF-2020Update Date
28-04-2024
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