Mechanics of intestinal organoids

Integrative cell and tissue dynamics · Xavier Trepat

 

Research project


Our group aims at understanding how physical forces and molecular control modules cooperate to drive biological function. We develop new technologies to map and perturb the main physical properties that determine how cells and tissues grow, move, invade and remodel. By combining this physical information with systematic molecular perturbations and computational models we explore the principles that govern the interplay between chemical and physical cues in living tissues. We study how these principles are regulated in physiology and development, and how they are derailed in cancer and aging.

 

Job position


The intestinal epithelium is a highly dynamic tissue that self-renews every 4 days. To achieve this, stem cells at the intestinal crypt constantly proliferate giving raise to new cells, which will then migrate to the tip of the villus and actively die. This process requires a tight control of cell division, cell movement and cell death to maintain tissue homeostasis. The loss of this tight homeostatic control is associated with cancer and inflammatory diseases. The regulation of epithelial growth, homeostasis and disease is determined not only by biological signals but also by mechanical ones such as cellular forces and stiffness. In this project, we will study the interplay between tissue biology and mechanics using intestinal organoids as a model system. The candidate will develop tools to quantify mechanics of organoids with high spatiotemporal resolution. These tools will involve advanced microscopy, nanotechnology, and image processing. Using these tools, the candidate will study the role of cell mechanics in organoid growth and morphogenesis, as well as how it is altered 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).