Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to un ....Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to understand how actinin-4, a component of the actin cytoskeleton in non-muscle tissues, interacts with and is stimulated by proteins of the intracellular signalling cascade.Read moreRead less
The mechanisms and roles of receptor clustering in cell activation and wound healing by growth factors. Growth factors regulate cell proliferation, migration and differentation by interaction with receptors. Such receptors are usually localized at the cell surface, and require intracellular transduction systems to transmit the signal to the cell interior. We have recently shown the hormone-induced clustering of heterologous hormone receptors in cells, and that this occurs with the co-clustering ....The mechanisms and roles of receptor clustering in cell activation and wound healing by growth factors. Growth factors regulate cell proliferation, migration and differentation by interaction with receptors. Such receptors are usually localized at the cell surface, and require intracellular transduction systems to transmit the signal to the cell interior. We have recently shown the hormone-induced clustering of heterologous hormone receptors in cells, and that this occurs with the co-clustering of downstream signalling molecules at sites of engagement with the extracellular matrix. In addition, we have found that cells presented with an extracellular matrix respond better to subsequent growth factor stimulation. The project aims to determine the cellular mechanisms underlying receptor clustering and the basis of the receptor-extracellular matrix interaction. This will enhance our understanding of growth factor function in a number of conditions, including wound healing. We will extend our in vitro results to the animal model to define parameters for enhanced wound repair.Read moreRead less