Project description
A star is born: how microtubule asters exert forces to move and position themselves
Microtubules (MTs), tiny hollow tubes in the cytoplasm, play an essential role in nuclear positioning and spindle orientation, thereby subserving cell polarity, division and development. MT asters are arrays of MTs radiating from the centrosomes, which are the primary microtubule organising centres in animal cells. The European Research Council-funded FORCASTER project will study the mechanisms by which MT asters exert forces to move and position themselves in vivo. These forces are generated at extremely small distances and fast time scales by MT-associated motors from sites in the cytoplasm or at the cell surface. Using in vivo biophysical experiments, the team will study aster micromechanics during sea urchin development.
Objective
Cells must move and position internal components to perform their function. We here focus on the physical designs which allow microtubule (MT) asters to exert forces in order to move and position themselves in vivo. These are arrays of MTs radiating from the centrosome, which fill up large portions of cells. They orchestrate nuclear positioning and spindle orientation for polarity, division and development. Forces that move asters are generated at nanometer and second scales by MT-associated motors from sites in the cytoplasm or at the cell surface. How MTs and force-generators self-organize to control aster motion and position at millimeter and hour scales is not known. We will use a suit of biophysical experiments and models to address how aster micro-mechanics contribute to aster migration, centration, de-centration and orientation in a single in vivo system, using the early stages of Sea urchin development as a quantitative model.
We aim to: 1) Elucidate mechanisms that drive aster large-scale motion, using sperm aster migration after fertilization during which asters grow and move rapidly and persistently to the large-egg center. We will investigate how speeds and trajectories depend on boundary conditions and on the dynamic spatial organization of force-generators.
2) Implement magnetic-based subcellular force measurements of MT asters. We will use this to understand how single force-events are integrated at the scale of asters, how global forces may evolve will aster size, shape, in centration and de-centration processes, using various stages of development, and cell manipulation; and to compute aster friction.
3) Couple computational models and 3D imaging to understand and predict stereotyped division patterns driven by subsequent aster positioning and aster-pairs orientation in the early divisions of Sea urchin embryos and in other tissues.
This framework bridging multiple scales will bring unprecedented insights on the physics of living active matter.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences cell biology
- natural sciences biological sciences developmental biology
- natural sciences biological sciences biophysics
- natural sciences mathematics pure mathematics geometry
- medical and health sciences clinical medicine embryology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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(opens in new window) ERC-2014-CoG
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75794 PARIS
France
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