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Symmetry breaking and self-organization in intestinal organoids

Symmetry breaking and self-organization in intestinal organoids

Symmetry breaking and self-organization in intestinal organoids

Friedrich Miescher Institute for Biomedical ¶¶Òõ¶ÌÊÓƵ (FMI)

Multicellular organisms are composed of cells and tissues with identical genomes but different properties and functions. They all develop from one cell to form multicellular structures of astounding complexity. During development, in a series of spatio-temporal coordinated steps, cells differentiate into different cell types and establish tissue-scale architectures and functions. Throughout life, continuous tissue renewal and regeneration is required for tissue homeostasis, which also requires fine-tuned spatio-temporal coordination of cells. I will discuss how cellular interactions generate the specific contexts and spatio-temporal coordination underlying development and regeneration and how we specifically develop new technologies to investigate what are the molecular and physical mechanisms that allow a cell, in a tissue, to sense its complex environment, to take individual coordinated decisions. Moreover, I will discuss the molecular mechanisms of intestinal organoid self-organization and the role of cell-to-cell variability in populations of differentiating cells during symmetry breaking.

Prisca Liberali has been trained as a physical organic chemist, and during her postdoc she has developed new single-cell methods and statistical approaches to model complex patterns of cell-to-cell variability. Since 2015, Prisca runs her research group at the FMI, in which she continues to innovate on image-based single-cell approaches. She has set up novel light-sheet and high-throughput imaging approaches to quantify organoids. This has recently led to a seminal paper by her group showing that initial symmetry breaking in intestinal organoids is determined by variation in mechano-sensing in individual cells. In addition, she has successfully applied this platform to achieve the first high-content screen of compounds that interfere with intestinal regeneration and identified novel compounds that improve intestinal regeneration in vivo.

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