Hallou Group | Cell and Tissue Dynamics

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 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 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 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, image-based force inference, atomic force microscopy (AFM), mathematical modelling and ML/AI.

2. To map the 'mechano-transcriptome' of mouse and human tissues in development, homeostasis and disease, with a particular focus on inflammatory diseases (psoriasis, IBD, uveitis) and cancer. 

3. To functionally characterise the biological and mechanical determinants of cell fate decisions using lineage tracing, intravital imaging and human organoid co-cultures with immune and stomal cells, combined with CRISPR-based genome editing and mechanical/biochemical perturbation experiments.