Objective
Antigen-stimulated naïve CD8+ T cells proliferate and differentiate into effector and memory cells. Whereas effector T cells remove infected or cancerous cells, memory T cells protect the organism from re-infections. Despite decades of research, the challenging central questions of how naïve T cells form diverse progeny and what drives the differential response of naïve and memory T cells to infection remain unanswered, largely because of lacking experimental tools.
The goal of this project is to generate a comprehensive model of cell-fate choices of naïve and memory CD8+ T cells in vivo. We will achieve this by addressing three complementary specific objectives:
1) To understand the early and late fate choices in naïve T cells.
2) To uncover differences between naïve and memory T-cell responses and fates.
3) To identify the role of proximal protein kinases LCK and FYN in T-cell fate choices.
We will pursue these aims using a combination of experimental immunology and systems biology. We used the synergy between novel genetic models and single cell atlases (i) to characterize an unprecedented transient stage of activated T cells, (ii) to determine the early gene expression signatures and fate choices of in vivo activated naïve and memory T cells, and (iii) to observe that LCK secures memory T-cell formation. These tools and findings offer us novel perspectives to tackle the challenging objective in its full complexity. We will develop additional unique experimental models coupled with innovative in-silico techniques to uncover the cellular and molecular mechanisms underlying diverse fate choices of particular T-cell subsets and to narrow the gap between mouse and human immunology.
Overall, this project has the ambition to resolve long-standing fundamental questions in immunology to open new avenues for targeting and modulating T-cell fates in vivo for efficient vaccine design and for promoting beneficial cytotoxic responses to chronic infections and cancer.
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. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- medical and health sciencesclinical medicineoncology
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
142 20 Praha 4
Czechia