SubsidieMeestersDeciphering stem cell immunity
This project investigates the stem cell-specific immune pathway aviD to understand its role in antiviral defense and transposable element regulation, aiming to enhance stem cell immunity and cancer therapies.
Projectdetails
Introduction
Stem cells guard tissue integrity by renewing the pool of differentiated cells and must therefore be shielded from threats such as transposable elements or viruses. In that line, stem cells can largely resist viral infections, but they do so without deploying the antiviral pathways at play in differentiated cells.
Research Question
So, what guards the guardians? I recently discovered a stem cell-specific immune pathway, driven by a protein termed aviD (antiviral Dicer), which mounts an antiviral RNA interference (RNAi) response and thwarts RNA virus infection. This illustrates that stem cells implement specific defense mechanisms that are poorly understood or unknown.
Proposal Overview
My proposal aims at bridging the current knowledge gap in stem cell immunity. We will do so by investigating the role of the aviD pathway in vivo using an aviD knock-out mouse, as well as by unravelling the molecular regulation of the pathway (Aim 1).
Aim 1: Investigating the aviD Pathway
- Investigate the role of the aviD pathway in vivo using an aviD knock-out mouse.
- Unravel the molecular regulation of the aviD pathway.
Aim 2: Exploring Transposable Elements
Stem cell demise can additionally be provoked by the expression of transposable elements (TEs). Converging evidence suggests that aviD and the RNAi pathway may play a second defensive role in shielding uninfected stem cells from TE expression, which we will explore in Aim 2.
- Study the role of aviD and the RNAi pathway in protecting stem cells from TE expression.
- Investigate aviD expression in various tumor models and assess its role in controlling TEs.
This is of special interest because awakening TE expression in cancer is being leveraged by new therapeutic approaches in multiple malignancies. Similarly, we will explore if inhibiting aviD and the RNAi pathway could have an antitumor effect (Aim 2).
Aim 3: Identifying Additional Pathways
Finally, I hypothesize that stem cells are protected by additional, unknown antiviral pathways, which we aim to identify and characterize using new genome-scale approaches (Aim 3).
Conclusion
Overall, this proposal aims at unveiling new biology in stem cell immunity as well as developing clinical applications in the field of antitumor therapy.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.500.000 |
| Totale projectbegroting | € 1.500.000 |
Tijdlijn
| Startdatum | 1-8-2023 |
| Einddatum | 31-7-2028 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- INSTITUT CURIEpenvoerder
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Land(en)
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