Objective
Populations of fibroblasts and related cells of mesenchymal tissues in vivo, include several subtypes expressing different isoforms of actins, especially the cells expressing or non-expressing a-smooth muscle actin (a-SM-positive and a-SM-negative cells). The aim of this project is to review and analyze the mechanisms determining different molecular and structural organization of focal adhesions in cells with various isoforms of actin.
This analysis will be based on the hypothesis is that the main differences between these isotypes are manifested by various expression of functions related to contractility of cortical cytoskeleton and mechanochemical interactions of these cells with the extracellular matrix. Cell shape, organization of focal adhesions with the matrix, pseudopodial activity of motile cells and traction exerted by these cells on the elastic substrata, will be compared in the a-SM-positive and a-SM-negative cells from several types of fibroblastic cultures. Reactions of a-SM-positive and a-SM-negative cells to the chemically and geometrically different substrata to which these cells will be attached will be examined. Expression of a-SM actin will be induced by cytokines (e.g. TGFb). Polymerization of a-SM actin will be selectively inhibited by the introduction into the cells of specific N-terminal decapeptide and alterations of cell characteristics induced by this inhibition will be examined. Preliminary data suggest that expression of a-SM actin increases contractility of actin cytoskeleton of fibroblasts, alters their adhesiveness and motility and in this way alters their relationships with the substrata of various compositions and shapes. The results of this project will reveal possible new molecular mechanisms of cytoskeleton contractility regulation and of cell-matrix relations, by changing the expression of various actin isoforms. These mechanisms may play a major role in normal morphogenesis and in its pathologic alterations, especially, in those accompanying neoplastic transformations.
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding Scheme
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Coordinator
1211 Geneva 4
Switzerland
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.