The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.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.
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
New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways res ....New insights into mammalian gene transcription - the role of parafibromin. Increasing our knowledge of fundamental gene and protein interactions is imperative as we move into an era of targetted molecular therapies to treat disease. Cancer is at the forefront of these diseases with hope of improved treatments firmly based in understanding the basic cell biology of tumours. This proposal describes research into a protein called parafibromin. We propose that parafibromin acts in major pathways responsible for how a cell manages stress by regulating levels of proteins involved in the cellular stress response. Discoveries made during the course of this research will provide knowledge of gene and protein interactions that will be important in the future to develop anti-cancer therapies. 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
Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to ....Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to discover the specificity of PAT-SM6 for proteins and protein complexes and how these interactions lead to tumour cell death. This work will enhance the effectiveness of human antibody therapies and help in the development of this fast growing area within the biotechnology industry in Australia.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
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
Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge ma ....Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge may also shed light on the basis of congenital abnormalities and other pathological processes and possibly help us to understand how to prevent or treat these conditions.Read moreRead less