Cell-to-cell variability during symmetry breaking in organoid development

Informacje na temat projektu

SymBreakOrganoid

Identyfikator umowy o grant: 758617

DOI

10.3030/758617

Projekt został zamknięty

Data podpisania przez KE 5 Września 2017

Data rozpoczęcia 1 Października 2018

Data zakończenia 30 Września 2023

Finansowanie w ramach

• EXCELLENT SCIENCE - European Research Council (ERC)

Koszt całkowity

€ 1 500 000,00

Wkład UE

€ 1 500 000,00

Koordynowany przez

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Switzerland

Periodic Reporting for period 4 - SymBreakOrganoid (Cell-to-cell variability during symmetry breaking in organoid development)

Okres sprawozdawczy: 2023-04-01 do 2023-09-30

Podsumowanie kontekstu i ogólnych celów projektu

The overall objectives of the project are to determine the cause and consequences of cellular heterogeneity in intestinal organoids. We have established novel experimental frameworks for analyzing collective behaviors of cells in tissue and develop perturbation methods to have improved spatio temporal resolution. This is allowing us to understand design principles of tissue development, homeostasis and regeneration. We are also developed tools to perturb individual cells and create synthetic heterogeneities in tissues. This then allowed us to translate some of our finding in human organoids and discover novel mechanisms of human intestinal regeneration.

Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty

For the grant we performed imaging multiplexed time course experiments of organoid development for determining the source of cell to cell variability and to predict symmetry breaking events. We then performed scRNAseq and ATACseq time course experiment to understand the extend of cell to cell variability. Finally, we built a light sheet microscope that allows us to follow the formation of organoids from one cell to a fully formed organoid to follow the consequence of cellular heterogeneity. We have implementing the optogenetic perturbations in the light sheet to control cellular heterogeneity.

Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)

The work establishes novel paradigm on how to analyzer collective behaviors. We also discovered that organoid development follow a regenerative response and this is having incredible implication in how to study regeneration in vitro, in mouse but also in human. It allowed us to test novel compounds in intestinal regeneration in vivo. Finally, it allowed us to set the standard in the field on how to perform image based analysis in organoids

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