| Project Detail |
3D co-culture and advanced techniques shed light on cell competition dynamics Cells compete for survival to regulate tissue architecture and function from early embryonic development to ageing. This ‘cell competition’ results in less fit cells being actively removed by their more fit counterparts. Given the tremendous temporal and spatial heterogeneity of competitive interactions, cell competition dynamics are difficult to study. The ERC-funded CELL-FIT project aims to investigate competition’s mechanisms, induction of long-term cell adaptations and contribution to tumour growth. An innovative 3D co-culture system and new toolbox will enable researchers to recognise and manipulate interacting and competing cells. Long-term quantitative imaging and single cell multi-omics will shed light on the dynamics of competitive behaviour at molecular, cellular and population scales. 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? |
