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Spatial and temporal regulation of cell competition

Descrizione del progetto

Co-cultura 3D e tecniche avanzate fanno luce sulle dinamiche di competizione cellulare

Le cellule competono per la sopravvivenza per regolare l’architettura e la funzione dei tessuti dallo sviluppo embrionale all’invecchiamento. Questa «competizione cellulare» fa sì che le cellule meno idonee vengano attivamente rimosse dalle loro controparti più idonee. Data l’enorme eterogeneità temporale e spaziale delle interazioni competitive, le dinamiche della competizione cellulare sono difficili da studiare. Il progetto CELL-FIT, finanziato dal CER, si propone di studiare i meccanismi della competizione, l’induzione di adattamenti cellulari a lungo termine e il contributo alla crescita tumorale. Un innovativo sistema di co-coltura 3D e un nuovo toolbox consentiranno ai ricercatori di riconoscere e manipolare le cellule che interagiscono e competono. L’imaging quantitativo a lungo termine e la multiomica di singole cellule faranno luce sulle dinamiche del comportamento competitivo su scala molecolare, cellulare e di popolazione.

Obiettivo

Every tissue in our body is a mosaic formed by individual cells that have different levels of cellular fitness. Competitive interactions, where the relative differences in fitness determine cell survival, therefore have a major impact on the physiology of a wide variety of tissues. Cell competition is versatile and abundant, and it impacts a broad spectrum of processes, ranging from early embryonic development to aging. Yet, due to the heterogeneity of competitive interactions, both in space and time, the dynamics of this process are difficult to unravel. For instance, it is unclear which long-term adaptations of cellular behavior cell competition induces. Furthermore, the consequences of a locally activated response on overall tissue fitness are unknown.

The overall objective of this project is to unravel spatial and temporal regulation of cell competition. Specifically, I aim to understand the:
1) Cell competition-driven adaptations of cellular behavior
2) Mechanistic regulation of competitive cellular interactions
3) Contribution of cell competition to tumor growth in different tissues

The foundation of this project is formed by our innovative 3D co-culture system which my team developed to dissect competitive behavior at molecular, cellular, and population scales. We will combine this system with a newly generated toolbox to recognize and manipulate interacting and competing cells. By leveraging our leading expertise in long-term quantitative imaging and single cell multi-omics, we will mechanistically untangle cell competition in primary intestinal cancer in space and time. To understand how competition affects different types of tumor growth and find shared regulators of this process, we will expand our co-culture systems to different tissues. Together, this provides the unique opportunity to tackle a fundamental question in cell biology: How is cell competition regulated in space and time and how does this impact tissue composition and tumor growth?

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-ERC - HORIZON ERC Grants

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(si apre in una nuova finestra) ERC-2024-COG

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Istituzione ospitante

UNIVERSITEIT UTRECHT
Contributo netto dell'UE
€ 1 999 993,00
Costo totale
€ 1 999 993,00

Beneficiari (1)