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Molecular control of actin network architecture and mechanics during cell shape changes

Project description

Role of actin architecture in cell morphogenesis

Animal cells contain dynamic networks of actin proteins which determine cell shape and movement. Understanding how changes in actin architecture are regulated will shed light on the mechanisms of cell deformation associated with various diseases. The EU-funded NanoMechShape project will investigate the actin cortex, the network of actin filaments that lies underneath the cell membrane. Using super-resolution and electron microscopy, researchers will investigate the impact of actin cortex structure on tension and cell shape. The project will provide important knowledge on the molecular processes underlying cell shape determination.

Objective

Precise control of shape is key to cell physiology, and cell shape deregulation is at the heart of many pathologies. As cell morphology is controlled by forces, studies integrating physics with biology are required to truly understand morphogenesis. NanoMechShape will take such an interdisciplinary approach to investigate the regulation of animal cell shape.
In animal cells, actin networks are the primary determinants of shape. Most cell shape changes fall into two categories: 1) those driven by contractions of the actin cortex, a thin network underlying the membrane in rounded cells; and 2) those resulting from transitions between the cortex and other actin networks, such as lamellipodia and filopodia. To understand cell deformations, it is thus essential to understand the regulation of cortex contractile tension and the mechanisms controlling transitions in actin architecture.
NanoMechShape will comprise three aims. First, we will explore how cortex tension is regulated. We will focus on the role of cortex architecture, which remains elusive due to the difficulty in probing the organisation of the thin cortical network. We will unveil cortex architecture using super-resolution and electron microscopy, and systematically investigate how nanoscale architectural features affect tension. Second, we will explore how the identified regulatory mechanisms contribute to the establishment of a cortical tension gradient. We will focus on the gradient driving cytokinetic furrow ingression, an exemplar tension-driven shape change. Third, we will investigate transitions in actin architecture underlying cell spreading. We will compare spreading at the end of mitosis and during differentiation of mouse embryonic stem cells, paving the way to investigations of the crosstalk between cell shape and fate.
By bridging a fundamental gap between molecular processes and cell-scale behaviors, our multidisciplinary study will unveil some of the fundamental principles of cell morphogenesis.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2018-COG

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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
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.

€ 1 943 071,00
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
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.

€ 1 943 071,00

Beneficiaries (1)

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