Isolation and analysis of novel caspases. Apoptosis is an evolutionarily conserved cellular process which must be tightly controlled for normal development and to avoid disease. Rapid progress has been made recently in the elucidation of apoptotic pathways, but many important components are likely still unknown. The caspases constitute the effector arm of apoptotic signalling pathways and some members play important roles in cytokine maturation. We aim to identify novel caspases using an innovat ....Isolation and analysis of novel caspases. Apoptosis is an evolutionarily conserved cellular process which must be tightly controlled for normal development and to avoid disease. Rapid progress has been made recently in the elucidation of apoptotic pathways, but many important components are likely still unknown. The caspases constitute the effector arm of apoptotic signalling pathways and some members play important roles in cytokine maturation. We aim to identify novel caspases using an innovative technique, and to characterise their function and regulation. Molecules identified in this project may be candidate targets for therapies which modulate apoptosis for treatment or prevention of disease, or diagnostic reagent development.Read moreRead less
Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. L ....Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. Leishmaniasis, recently found in Australia, is a risk for overseas travellers, livestock and wildlife. This research will provide an understanding of what makes these parasites successful, paving the way for development of novel drugs to combat these chronic diseases.Read moreRead less
Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins ....Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins of interest by conventional proteomic methods. The establishment of SELDI-MS as a viable tool for cell proteomics would open new opportunities to understand a broad range of cellular functions at the level of protein expression.Read moreRead less
INTRINSIC PROPERTIES OF THE PORE FORMING DOMAIN OF THE RYANODINE RECEPTOR CALCIUM CHANNEL. The project is to understand how a calcium ion channel is able to regulate muscle performance. The ion channel, known as the ryanodine receptor, is essential for human and animal survival. The results of the project will be integral to understanding muscle performance in humans and will have long term implications for Australian sports physiology and sports science. The project will also be integral to ....INTRINSIC PROPERTIES OF THE PORE FORMING DOMAIN OF THE RYANODINE RECEPTOR CALCIUM CHANNEL. The project is to understand how a calcium ion channel is able to regulate muscle performance. The ion channel, known as the ryanodine receptor, is essential for human and animal survival. The results of the project will be integral to understanding muscle performance in humans and will have long term implications for Australian sports physiology and sports science. The project will also be integral to understanding muscle performance and development in animals and will have repercussions for the Australian livestock and racing industries. The results may lead to the development of new insecticides since insect mobility depends on ryanodine receptor activity. This will benefit to Australian agriculture.Read moreRead less
Cholesterol-dependent control of plasma membrane lipid rafts. Lipid rafts are recently discovered micro-domains in the plasma membrane that are highly enriched in cholesterol, giving these domains a unique lipid structure. Because of their distinct structure specific proteins partition into these domains so that lipid rafts act as message transduction centres in a variety of cell functions. It is hypothesised that cholesterol is the link between the distinct biophysical parameters of lipid rafts ....Cholesterol-dependent control of plasma membrane lipid rafts. Lipid rafts are recently discovered micro-domains in the plasma membrane that are highly enriched in cholesterol, giving these domains a unique lipid structure. Because of their distinct structure specific proteins partition into these domains so that lipid rafts act as message transduction centres in a variety of cell functions. It is hypothesised that cholesterol is the link between the distinct biophysical parameters of lipid rafts and their function. The aim of this proposal is to understand how cellular cholesterol levels contribute to raft structure and function, thus elevating cholesterol to a regulatory element for lipid raft and their function.Read moreRead less
Development of novel fluorescent proteins from marine organisms for in vivo fluorescence imaging technologies and cancer research. The Australian Great Barrier Reef (GBR) is a national treasure and the development of fluorescent proteins (FPs) from reef organisms for in vivo imaging and biotechnology will enhance the appreciation of this resource. Nowadays, imaging of biochemical processes in living cells is essential for knowing the roles of various genes and proteins in health and diseases. Th ....Development of novel fluorescent proteins from marine organisms for in vivo fluorescence imaging technologies and cancer research. The Australian Great Barrier Reef (GBR) is a national treasure and the development of fluorescent proteins (FPs) from reef organisms for in vivo imaging and biotechnology will enhance the appreciation of this resource. Nowadays, imaging of biochemical processes in living cells is essential for knowing the roles of various genes and proteins in health and diseases. The global market for fluorescence-based products is estimated in billions of dollars p.a. The discovery of natural FPs from GBR with superior molecular, biophysical and optical characteristics to those of commercially available FPs offers a unique opportunity to develop advanced tools to study cellular processes and develop diagnostic assays for diseases such as cancer.Read moreRead less
Proteolysis of binding protein complexes regulates bioavailability of insulin-like growth factor (IGF). We aim to determine how growth factors kept inactive in complexes in the blood can become free and active. The fundamental knowledge gained will help us understand the regulation of growth factors' availability to tissues and develop novel or more effective delivery systems for therapeutic growth factors that could impact on several conditions including diabetes, growth disorders and critical ....Proteolysis of binding protein complexes regulates bioavailability of insulin-like growth factor (IGF). We aim to determine how growth factors kept inactive in complexes in the blood can become free and active. The fundamental knowledge gained will help us understand the regulation of growth factors' availability to tissues and develop novel or more effective delivery systems for therapeutic growth factors that could impact on several conditions including diabetes, growth disorders and critical illness. This project therefore benefits Australia at two levels: by maintaining our international leadership in the study of these important growth-regulatory molecules, and by providing a better understanding of physiological mechanisms that might benefit the health of Australians and provide opportunities to develop novel therapeutics.Read moreRead less
How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by wh ....How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by which clusterin effects its protective actions. We expect to demonstrate that clusterin protects cells form stresses by exerting its chaperone action at or near the cell surface and to identify specific regions and structural features of the clusterine molecule important in its chaperone action.Read moreRead less
Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens ....Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens of which account for billions of dollars and millions of Australians. This project aims to understand one of the major mechanisms that controls cell migration, which is expected to produce significant economic and social outcomes in the areas of basic science knowledge, human health, and biotechnology. Read moreRead less
Beyond access: women, higher education and the quiet revolutions of the 1950s. This project challenges the standard narrative of women in the 1950s through a study of the intersections of higher education, gender and place. By studying women graduates in Australia and the United States within the context of demographic, employment and cultural change, it develops life histories of graduate women over several decades of their post-universtiy lives, drawing on comparative sources. It offers a new ....Beyond access: women, higher education and the quiet revolutions of the 1950s. This project challenges the standard narrative of women in the 1950s through a study of the intersections of higher education, gender and place. By studying women graduates in Australia and the United States within the context of demographic, employment and cultural change, it develops life histories of graduate women over several decades of their post-universtiy lives, drawing on comparative sources. It offers a new framework for women's educational history, one that goes beyond access and focuses on the new identities that were formed as graduate women negotiated the contradictions of higher education and the dominant femininity of the period.Read moreRead less