Activation and switch of fates in T lymphocytes.
This project aims to model the fate choices of naïve and memory CD8+ T cells using experimental immunology and systems biology to enhance vaccine design and improve responses to infections and cancer.
Projectdetails
Introduction
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.
Project Goal
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:
- To understand the early and late fate choices in naïve T cells.
- To uncover differences between naïve and memory T-cell responses and fates.
- To identify the role of proximal protein kinases LCK and FYN in T-cell fate choices.
Methodology
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 to:
- Characterize an unprecedented transient stage of activated T cells.
- Determine the early gene expression signatures and fate choices of in vivo activated naïve and memory T cells.
- 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.
Future Directions
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.
Conclusion
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.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 2.625.000 |
Totale projectbegroting | € 2.625.000 |
Tijdlijn
Startdatum | 1-1-2025 |
Einddatum | 31-12-2029 |
Subsidiejaar | 2025 |
Partners & Locaties
Projectpartners
- USTAV MOLEKULARNI GENETIKY AV CR V.V.I.penvoerder
Land(en)
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This project aims to uncover the signals and mechanisms behind the clonal memory of human NK cells to enhance their effector functions and identify new targets for anti-tumor therapies.
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This project aims to elucidate the biology and regulation of follicular helper T cells to enhance understanding of germinal center dynamics, improving vaccine and therapeutic strategies against pathogens.
Engineered symbionts elucidate gut T cell memory and its (dys)regulation
The GuT Memory project aims to uncover the mechanisms of microbiota-directed Th cell memory to enhance vaccine design and target pathogenic T cells in inflammatory bowel disease.
Tracking adaptation of naïve T cells to distinct organs to decode organ-specific immune diseases
This project investigates how organ-adapted naïve CD4+ T cells contribute to organ-specific immune-mediated inflammatory diseases triggered by environmental factors, aiming to enhance precision medicine approaches.
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