Hallou Group | Cell and Tissue Dynamics

Epithelial tissues are in a constant state of renewal. To ensure their maintenance, stem cells divide and differentiate to replace cells lost through exhaustion and damage. However, the mechanisms that control epithelial stem cell renewal and the pathways that lead to their dysregulation in disease remain debated. Our work investigates how mechanical and biochemical signals, particularly those associated with extracellular matrix, stromal and immune cells, combine to regulate epithelial stem cell fate decisions in development, homeostasis and disease. To that aim we develop innovative experimental and computational approaches that combine mechanobiology, spatial genomics, advanced microscopy, machine learning / artificial intelligence and mathematical modeling to study the mechanical and biochemical environment of in vivo tissues and organoid cultures at single cell resolution. Our work is highly interdisciplinary, and we actively collaborate with biologists, clinicians, but also mathematical biologists, bio-statisticians and computer scientists.

Aim

Develop new computational and experimental tools to understand the role of mechanical and biochemical signals in cell fate decisions and tissue dynamics in development, homeostasis, regeneration and disease.

Objectives

1. To develop an integrated spatial 'mechano-omics' platform to measure the molecular and mechanical state of cells in tissues at single resolution using advanced microscopy, spatial genomics, atomic force microscopy (AFM), mathematical modelling and AI;

2. To map the 'mechano-transcriptome' of mouse and human tissues (skin, colon, tumours, etc) in homeostasis, regeneration and inflammation;

3. To unravel the biological and mechanical determinants of epithelial stem cell fate decisions using lineage tracing and intravital imaging with transgenic mouse models and human organoid co-cultures with immune and stomal cells, in combination with CRISPR-based genome editing and mechanical / biochemical perturbation experiments.