Mechanobiology of intestinal organoids

Group: Integrative cell and tissue dynamics
Group leader: Xavier Trepat (xtrepat@ibecbarcelona.eu)

The intestinal epithelium is a highly dynamic tissue that self-renews every 3-5 days. Epithelial self-renewal is achieved through the action of stem cells that reside at the bottom of highly curved tissue compartments termed intestinal crypts. Intestinal stem cells constantly divide, giving rise to new cells that leave their niche, proliferate in the crypt neck, differentiate into distinct cell types, and migrate to the tip of dome-like protrusions called villi, where they are extruded into the intestinal lumen. Each of these processes is governed not only by biological signals but also by mechanical ones such as cellular forces and tissue stiffness. The goal of this PhD project will be to study how tissue biology and mechanics work together to generate and maintain the shape and function of intestinal organoids. The student will combine tools in life cell microscopy, mechanobiology, cell and molecular biology, organoid models, and 3D bioprinting. In addition, the project will rely on novel technologies developed in our laboratory including optogenetic probes and force mapping methods (Latorre et al, Nature, 2018). The project will be carried out in collaboration with world experts in organoid biology (Danijela Vignjevic, Institut Curie), cancer biology (Eduard Batlle, IRB Barcelona), and computational mechanics (Marino Arroyo, UPC).

The candidate will develop tools to quantify mechanics of organoids with high spatiotemporal resolution. These tools will involve advanced microscopy, force mapping methods, nanotechnologies, biomaterials, and organoid biology. Using these tools, the candidate will study the role of cell mechanics in organoid growth and morphogenesis, as well as its alteration in colorectal cancer.

References:

1. Latorre E, …, Trepat X. Active superelasticity in epithelial domes of controlled geometry. Nature (2018).

2. Labernadie A, …, Trepat X. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nature Cell Biology (2017).

3. Sunyer R, …, Trepat X. Collective cell durotaxis emerges from long-range intercellular force transmission. Science (2016).