Objective
Cell-to-cell variability is an inherent property of populations of cells. As a starting point for symmetry breaking events, it is also an essential building block for self-organised pattern forming systems. Nonetheless, the sources and roles of cell-to-cell variability in symmetry-breaking events during collective cell behavior await a quantitative and mechanistic understanding. To obtain these insights, we will use a model system of intestinal organoids, which recapitulates most of the processes of morphogenesis and patterning observed in intestinal tissue. In this system, the symmetry-breaking event is observed when, despite all single cells in a growing organoid are exposed to uniform environments, only a fraction of cells acquires specific cell fates, generating asymmetric structures such as crypts and villi. This project aims to uncover the extent, sources, and consequences of cell heterogeneity. To this end, we will use advanced multiplexed imaging of intestinal stem cells in 3D organoid development to monitor quantitatively the behaviour of each single cell in the system. Initially, we will identify potential sources of cell-to-cell variability, such as the microenvironment or the cell cycle. Next, we will create models to identify predictors of symmetry breaking and patterning. In parallel, we will determine the extent of cellular heterogeneity by single-cell RNA sequencing during organoid formation. Finally, we will test if cellular heterogeneity is necessary and sufficient to induce symmetry-breaking of intestinal organoids by experimentally inducing and perturbing cell-to-cell variability. Thus, this research proposal will address a major question in developmental biology and collective cell behavior, namely how single cells exposed to a uniform growth-promoting environment generate asymmetric structures. Moreover, it will unravel how local interactions between single cells give rise to emergent, self-organized patterns.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences developmental biology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics RNA transcriptomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-STG - Starting Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2017-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
4056 BASEL
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.