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Chiral Morphogenesis - Physical Mechanisms of Actomyosin-Based Left/Right Symmetry Breaking in Biological Systems

Objective

The aim of this grant is to understand how cellular, tissue-scale and organismal left-right asymmetry arises
from the chirality of molecular constituents. In many instances the actomyosin cortex, a thin and
mechanically active layer of dynamically cross-linked filaments and molecular motors at the surface of cells,
drives the emergence of chiral morphogenetic events. In the nematode Caenorhabditis elegans, mesoscale
chiral active torques generated by this active layer establish the embryo’s left-right body axis. Here we want
to understand how mesoscale actomyosin active torques are generated at the molecular level, and how active
torque generation in the actomyosin surface drives chiral morphogenesis of cells, tissues and organisms.
Cells and tissues represent a new class of active chiral materials where both the force and the torque balance
need to be considered, and we will perform a systematic and cross-scale characterization of active chiral
biological matter. We will pursue an interdisciplinary approach at the interface of physics and biology. At the
molecular-scale, we will use optical tweezers to measure active torques generated by single molecules of the
molecular myosin and the actin polymerizing protein formin. At the cell-scale, we will reconstitute chiral
actomyosin flows in vitro and characterize chiral dynamics of single molecules in vivo. At the tissue-scale,
we will investigate chiral cell movements in a multicellular environment and unravel the physical basis of
chiral tissue flow in vertebrates. Theory is essential at all stages, and we will build a molecular-scale model
of actomyosin torque generation that will be coarse-grained to a generalized hydrodynamic description of
active chiral matter. This interdisciplinary and cross-scale approach will provide fundamentally new insights
into active chiral materials and the mechanisms by which left-right asymmetries arise in development.

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2016-ADG

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Host institution

TECHNISCHE UNIVERSITAET DRESDEN
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.

€ 2 500 000,00
Address
HELMHOLTZSTRASSE 10
01069 Dresden
Germany

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Region
Sachsen Dresden Dresden, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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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.

€ 2 500 000,00

Beneficiaries (1)

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