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Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells

Objective

Cell migration is centrally involved in embryonic development, regeneration and immune surveillance. However, when misguided it also contributes to the pathogenesis of Europe’s socioeconomic most relevant diseases including cancer, cardiovascular diseases and chronic inflammation. Accordingly, better understanding the fundamental mechanisms of cell migration is of direct clinical relevance. In order to migrate within a multicellular context, cells have to negotiate physical constraints, such as other cells and the extracellular matrix and effectively integrate mechanical challenges into directional decision-making. This proposal suggests a combined cell biological and biophysical approach to provide a quantitative understanding of the underlying molecular and mechanical principles. We will focus on the prototypic force-generating structure of migrating cells the lamellipodium - a flat sheet-like protrusion of dendritic actin networks at the leading front of migrating cells. We will decipher the ultrastructural adaptations of lamellipodial actin networks with single filament resolution and characterize how nucleation, elongation, depolymerization and crosslinking of actin filaments coordinate circumnavigation of mechanical obstacles. Technically, these questions will be addressed in a multidisciplinary approach by employing correlative fluorescence and electron tomography in combination with artificial environments engineered using microfluidics and substrate micropatterning, as well as genetic approaches and biological modelling. Importantly, findings will ultimately be challenged in living tissues. The expected results will generate an integrated view of force-adaptations of actin networks in living cells and will not only impact the fields of cell biology and biophysics but also cancer biology, immunology and developmental biology.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2016

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Coordinator

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
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.

€ 178 156,80
Address
Am Campus 1
3400 KLOSTERNEUBURG
Austria

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Region
Ostösterreich Niederösterreich Wiener Umland/Nordteil
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.

€ 178 156,80
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