Keeping stem cells on track: maintaining organ and tissue homeostasis. The novel findings from this study are of fundamental importance of understanding how stem cells maintain their characteristic features as they renew themselves over a lifetime. This work will inform the National Research Priority of ''Promoting and maintaining good health''' because stem cell renewal is required during tissue turnover and these results will show how cells communicate with each other to achieve this.
This wo ....Keeping stem cells on track: maintaining organ and tissue homeostasis. The novel findings from this study are of fundamental importance of understanding how stem cells maintain their characteristic features as they renew themselves over a lifetime. This work will inform the National Research Priority of ''Promoting and maintaining good health''' because stem cell renewal is required during tissue turnover and these results will show how cells communicate with each other to achieve this.
This work is based on a unique combination of expertise in stem cell and reproductive biology and showcases Australian science.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
Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity ....Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity, insulin resistance and various forms of cancers is well established) are leading to a rapid increase in new cancer cases, thus driving a rapid increase in demand for better treatments. This is particularly relevant in Indigenous health where obesity is on the rise following the transition from a traditional to an urban lifestyle.Read moreRead less
Differentiation of Cord Blood Stem cells into Thymus (T) cells with regulatory phenotype and function. This project will develop technologies for a stem cell therapy platform based on cord blood stem cells, to enable treatment of autoimmune diseases or transplants. Building on the University of Adelaide's frontier demonstration of differentiation of regulatory Thymus (T) cells from cord blood stem cells, the project will develop techniques to expand the numbers of T cells generated. This has the ....Differentiation of Cord Blood Stem cells into Thymus (T) cells with regulatory phenotype and function. This project will develop technologies for a stem cell therapy platform based on cord blood stem cells, to enable treatment of autoimmune diseases or transplants. Building on the University of Adelaide's frontier demonstration of differentiation of regulatory Thymus (T) cells from cord blood stem cells, the project will develop techniques to expand the numbers of T cells generated. This has the potential to maintain Australia's lead in differentiation of cord blood stem cells and to provide a significant breakthrough in potential treatments of autoimmune diseases (e.g. type 1 diabetes) or transplantation. These diseases affect both a healthy start to life and healthy ageing, and an Australian invention to treat or cure them would have global impact.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less
Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel ta ....Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel targets and strategies for treating obesity. The proposed study will also benefit Australian agriculture by providing strategies to improve oil production from plant seeds. Read moreRead less
Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the ....Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the Golgi remain largely unknown. We have recently cloned a novel ATP-binding protein specifically expressed at the Golgi apparatus in human brain, and hypothesise that this protein regulates Golgi protein trafficking by interacting with two other molecules, dynamin and calcium, during cell secretion.Read moreRead less
Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to u ....Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to utilise this technology to identify novel insulin-sensitising agents. These agents will be used for drug discovery purposes by our industry partner ChemGenex and as novel tools to dissect the mechanism of insulin action.Read moreRead less
Insulin-like growth factor binding proteins: structure and ligand interactions. Insulin-like growth factors are important for normal growth and development. Their actions are regulated by a family of IGF binding proteins. In order to understand the mechanism of this regulation, the aim of this project is to determine the 3-dimensional structure of 2 IGFBPs in complex with IGFs. This will lead to a comprehensive understanding of this interaction that promises to provide important basic knowledge ....Insulin-like growth factor binding proteins: structure and ligand interactions. Insulin-like growth factors are important for normal growth and development. Their actions are regulated by a family of IGF binding proteins. In order to understand the mechanism of this regulation, the aim of this project is to determine the 3-dimensional structure of 2 IGFBPs in complex with IGFs. This will lead to a comprehensive understanding of this interaction that promises to provide important basic knowledge as well as having major implications for biotechnology, agriculture and health.Read moreRead less
Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregul ....Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregulation of the IGF system has been implicated including cancer, diabetes and atherosclerosis.
Since IGFs are major determinants of growth, the outcomes of this project could also lead to improvements in animal production with major benefit to primary industry. New IGF analogues developed could assist biotechnology exports.
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