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The role of cell type-specific timing in the robustness of development

Objective

Reproducibility in development is maintained via precisely-timed execution of gene regulatory programs required to build all cell types of the embryo. However, many perturbations challenge this robustness and accelerate developmental tempo, leading to increased phenotypic variability. Mechanisms underlying this century-old observation have been obscured by variation inherent to embryogenesis, but advances in statistical single-cell profiling have revealed an unappreciated source of variability: non-uniform progression of development across cell types. Here, I propose to use a combination of ultra-scalable single-cell genomics, cross-species alignment of developmental trajectories, and engineering of developmental rate to understand how cell type-specific timing differences influence reproducibility of development. First, comparing vertebrate species with natural tempo differences, fast-developing zebrafish (Danio rerio) and slow-developing medaka (Oryzias latipes), we aim to generate time-resolved single-cell transcriptomic profiles and map variation in cell type-specific timing. We will relate timing variation to a quantitative robustness measure derived from cell composition profiles for hundreds of embryos, asking how the tempo of development influences its ability to reproducibly build a well-proportioned animal. Second, we aim to identify cell type-specific drivers of timing and coordination. Specifically, we will modulate tempo embryo-wide and test for proportional timing changes across cells by tracking responses to perturbation at the cell type level. We will then use genetic tools to promote lineage-specific acceleration of development, assessing the embryo’s capacity to compensate for an induced asynchrony. In challenging coordinated developmental progression in evolutionary, perturbation, and synthetic contexts, we will resolve how timing impacts reproducibility in development.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-STG

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Host institution

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution

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.

€ 1 648 555,00
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Links
Total cost

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.

€ 1 648 555,00

Beneficiaries (1)

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