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Building Distinct Actin Filament Networks in a Common Cytoplasm

Objective

"The ability of cells to use the actin cytoskeleton for a diversity of cellular processes is due to the fact that actin filaments, although assembled from identical subunits, are organized in a wide variety of structures of appropriate geometrical, dynamical and rheological properties. Key players in this regulation are specific sets of actin binding proteins (ABPs) interacting with each actin networks, to modulate spatially and temporally their properties.
With this project, I want to understand 1/ how cells can generate the formation of actin structures of appropriate ABP composition from a common pool of cytoplasmic components and 2/ the relationship between the ABP composition of an actin network, its geometrical and dynamical properties, and its response to mechanical deformations.

I will hypothesize that the generation of an actin network of appropriate ABP composition can be explained with an original model, taking into account the facts that 1/ actin filaments in cells are not all structurally identical, but adopt specific conformations that are favored and stabilized by certain families of ABPs; and 2/ the interaction of ABPs with actin depends of the geometrical organization of the filaments.

Because this project imposes to study protein-protein interactions in the presence of multiple partners, I propose to develop an unprecedented strategy combining 1/ ""bottom-up"" reconstitutions, where limited sets of ABPs are added one-by-one in the system to understand their combined activities with actin; and 2/ ""top-down"" reconstitutions with protein extracts prepared from a genetically-tractable organism (the yeast S. cerevisiae), where proteins can be removed one-by-one, in order to study actin network properties in near-physiological conditions.

This project will shed a new light on how cells organize their interior, and will represent a unique opportunity to understand how modifications in the expression of ABPs are associated with actin network defects.
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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 1 500 000,00
Address
Rue Michel Ange 3
75794 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00

Beneficiaries (3)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
Net EU contribution
€ 1 500 000,00
Address
Rue Michel Ange 3
75794 Paris

See on map

Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00
COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

Participation ended

France
Net EU contribution
€ 0,00
Address
Rue Leblanc 25
75015 Paris 15

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

Participation ended

France
Net EU contribution
€ 0,00
Address
Rue Michel Ange 3
75794 Paris

See on map

Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00