Project Reference: TRG27-GEN-BS1

Project title: Quantitative imaging of matrix-guided collective cell invasion in gastruloids

Project outline

How are cell movements and cell fate decisions coordinated to drive collective cell behaviour? This project will investigate how extracellular matrix (ECM) environments guide collective cell invasion and lineage commitment in mouse gastruloids, a 3D stem cell model of early embryonic development. It will build on recent working showing how embedding gastruloids in fibrin promotes collective invasion and biases differentiation towards cardiac and vascular lineages. It will first combine multi-view light-sheet microscopy, spinning disk imaging, and high-throughput imaging pipelines to resolve invasion dynamics, ECM organisation, and reporter expression in space and time. Existing fluorescent ECM reporters and lineage reporters will be used to determine how fibronectin and laminin remodelling relates to cell movement and the emergence of cardiovascular progenitors. Image analysis will include 3D cell tracking, morphometric analysis, and quantitative comparison of ECM organisation across conditions. It will then investigate how invasion is linked to signalling and fate. Hyper-plexed HCR and immunostaining will be used to map pathway activity and lineage marker expression in embedded gastruloids, then used to test whether defined extracellular environments can be used to modulate invasion mode and cell fate. Alongside fibrin, a focused set of defined matrix conditions will be explored to determine how matrix composition and physical properties influence invasion behaviour, tissue morphology, and lineage balance. This will provide a direct test of the idea that the acellular environment is not merely permissive but can guide self-organisation in organoids. The student will be embedded in an inter-disciplinary team spanning developmental biology, advanced microscopy, image analysis, and bioengineering. As such, the project provides an opportunity to bridge embryology with quantitative and biophysical approaches to tissue self-organisation.

Principal Supervisor

Professor Ben Steventon

Email address: bjs57@cam.ac.uk

Department / Partner Institute: Genetics

Website: https://steventonlab.wordpress.com/

BBSRC strategic theme

Understanding the rules of life