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

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.

Field of science

  • /medical and health sciences/basic medicine/pathology
  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/basic medicine/physiology

Call for proposal

ERC-2018-COG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 943 071

Beneficiaries (1)

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 1 943 071
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments