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Control mechanisms and robustness of multicellular symmetry breaking

Project description

Understanding symmetry breaking in animal development

Understanding how an animal’s body plan develops is a challenge. It is hampered by the gap between genetic and biophysical research and the lack of methods to recreate multicellular tissue organisation. The ERC-funded BREAKDANCE project aims to investigate early animal development, specifically how cell differentiation breaks symmetry and establishes the body axis. It will uncover the mechanisms behind this process by examining tissue geometry, physical boundaries, and cell interactions. Key questions include how shape, size, and geometry influence cellular behaviour and cell fate across species. Using mouse, zebrafish, and human embryonic stem cells, the project will develop new methods to study tissue dynamics. The results will contribute to the design of artificial tissues and organs.

Objective

Understanding the establishment of an animal body plan is an important challenge of modern biology. Progress has been mainly limited by (1) a separation of research fields studying genetic and biophysical mechanisms, and (2) a lack of approaches to mimic multicellular tissue organization from first principles. In a cross- disciplinary effort, we will focus on the earliest stages of animal development, when first steps of cell differentiation define the primary body axis through spatial symmetry breaking, laying the foundation for the future body plan. Our goal is to identify the fundamental mechanisms controlling this symmetry breaking process. To this end, we will study in detail the interplay between global tissue geometry (shape, size, and dimension), physical boundary conditions, and mechano-chemical cell interactions. Therefore, we address the following questions: (i) How do global shape and size control local cellular states and interactions? (ii) How do local cellular states and interactions induce robust symmetry breaking at the tissue level? (iii) To which extent can geometry control cell fate specification in a species-independent manner? To overcome previous limitations, we will establish a comprehensive methodological toolbox of synthetic bottom-up approaches and functional ex-vivo assays. We use as model systems mouse, zebrafish, and later also human embryonic stem cells. This will be combined with advanced biophysical techniques and theoretical modeling in order to systematically dissect the mutual couplings between genetic patterning mechanisms and morphogenetic processes, thereby revealing the multicellular dance underlying tissue symmetry breaking. Our results will shed new light on the long-standing question of how complex biological forms are robustly built from a single fertilized egg, impacting on our understanding of organism development and maintenance, and opening new directions for the controlled design of artificial tissues and organs.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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Call for proposal

(opens in new window) ERC-2022-SYG

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Host institution

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution
€ 2 841 355,00
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany
Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Links
Total cost
€ 2 841 355,00

Beneficiaries (4)