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Expression And Role Of Integrins During Lens Development And Cataractogenesis
Funder
National Health and Medical Research Council
Funding Amount
$336,760.00
Summary
Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous rese ....Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous research, which has identified molecules (growth factors) that are involved in either the regulation of normal lens development and growth (FGF and TGF-beta) or the induction of cataractous changes in the lens epithelium (TGF-beta). The studies are directed at identifying members of an important family of cell adhesion molecules, the integrins, in the lens and examining the role that these molecules play in controlling lens structure and function. These cell surface glycoproteins function in adhesion of cells to each other and to extracellular matrix, and transmit signals in response to changes in the extracellular environment. Such responses include cell proliferation, migration and differentiation. In this regard they often act in concert with growth factor receptors (eg. FGF and TGF-beta). After defining where and when integrins are expressed in the developing lens we will investigate their function in mediating various lens cell responses by using genetic manipulations to alter the expression of integrins or their intracellular signaling mediators in lenses of transgenic mice. In addition, a lens explant culture system will be used to investigate the roles integrins play during lens development and during formation of anterior subcapsular cataract by TGF-beta. These studies will provide important insights into the molecular mechanisms that control cellular events in normal and abnormal lens development.Read moreRead less
Tissue Regeneration In Oral Health: Regenerating Damaged Oral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$575,833.00
Summary
The regeneration of damaged dental tissues is an emerging area in oral health-based research and is increasingly becoming the forefront of medical-dental interdisciplinary investigations. This idea of repairing damage follows Dr Fiona Wood's unique concept of growing large amounts of specific cells in the lab and spraying them onto damaged tissue, which effectively assists in the repair of the damaged organ. This approach can be similarly used in the dental field by applying prosthetic implants ....The regeneration of damaged dental tissues is an emerging area in oral health-based research and is increasingly becoming the forefront of medical-dental interdisciplinary investigations. This idea of repairing damage follows Dr Fiona Wood's unique concept of growing large amounts of specific cells in the lab and spraying them onto damaged tissue, which effectively assists in the repair of the damaged organ. This approach can be similarly used in the dental field by applying prosthetic implants with cells and growth factors, thus enhancing the regeneration of the damaged dental tissue. Artificial replacement of missing teeth has significant limitations when compared with the natural, original tissues in terms of function and appeal. Bridges and dentures have been used for centuries in dentistry but require periodic maintenance or even replacement after a period of time due to usage or loss of adaptation. Thus, if implants and bridgework can be eliminated, so too will be the problems and costs associated with them. This benefit is specifically aimed at the regional community and the public sector, as these patients are generally not in a financial position to restore missing teeth with bridgework, let alone implants. Our aims are: 1. Examine the function of two recently identified growth factors, Osteoclast-Derived Osteoblastic Factor and Emilin and Multimerin-2, through their effect on paradental in vitro cell regeneration. 2. To assess the role played by collagen bioscaffolds, together with explanted cells and growth factors examined during the in vitro studies, in the healing process by comparing teeth transplanted into an existing socket with those transplanted into a prepared site. 3. Evaluate the effect of growth factors, explanted cells and bioscaffolds on regeneration of tissues lost as a result of ligature-induced periodontal infection.Read moreRead less