Spatial and temporal regulation of cell competition

Introduction

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.

Challenges in Understanding Cell Competition

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.

Project Objectives

The overall objective of this project is to unravel the 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

Methodology

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.

Research Techniques

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.

Fundamental Questions

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?