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Chaperone modulation of cell-matrix adhesion

Supervisor: Nick Brown

This project has arisen from our recent discovery that a protein chaperone pathway plays an important role in cell-matrix adhesion. Cell-matrix adhesion is required for cell migration and to maintain adhesion between cell layers, such as epithelial cell layers in the skin and muscle attachments to tendons. The activity of this chaperone could prevent the formation of protein aggregates that result from hydrophobic protein-protein interactions, as described in aggregation myopathies such as myofibrillar myopathies in Human. The proposed project aims to use the model organism Drosophila to identify the proteins responsible for recruiting the chaperone to adhesion sites and to understand how this impacts on the organisation of the adhesion complex. This involves using an in vivo imaging assay for protein recruitment, to search for proteins of the adhesion complex that can recruit and/or are recruited to chaperone regulatory subunits. The project will also use molecular cloning and genetics to generate mutants in candidate genes and transgenic flies expressing fluorescently tagged chaperone regulatory subunits. These will be imaged in the whole organism, in normal or mutant contexts, to assess their contribution to adhesion formation. Altogether, the results obtained will be used to design models to further test experimentally.

Relevant references

Maartens AP, Brown NH. (2015) The many faces of cell adhesion during Drosophila muscle development. Dev Biol. 401, 62-74.

Klapholz B, Herbert SL, Wellmann J, Johnson R, Parsons M, Brown NH. (2015) Alternative mechanisms for talin to mediate integrin function. Curr Biol. 2015 25, 847-857

Maartens AP, Wellmann J, Wictome E, Klapholz B, Green H, Brown NH. (2016) Drosophila vinculin is more harmful when hyperactive than absent, and can circumvent integrin to form adhesion complexes. J Cell Sci. in press

 

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