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
Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors ....Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors remains unknown. Our project will specifically investigate novel molecular mechanisms associated with serotonin receptor activity that may prove vital in understanding mechanisms of psychiatric illnesses, and how many psychiatric medicines actually work.Read moreRead less
The role of the Ttyh1 protein in cell activation. We have cloned TTYH1, a human homologue of the Drosophila melanogaster tweety gene. The mouse gene has also been identified. The predicted structure of the protein is a membrane protein with 5 transmembrane domains. We have also expressed a GFP-tagged fusion protein in mouse fibroblasts. Confocal microscopy indicates that this protein is likely to be a novel adhesion molecule, with a cellular distribution characteristic of molecules such as integ ....The role of the Ttyh1 protein in cell activation. We have cloned TTYH1, a human homologue of the Drosophila melanogaster tweety gene. The mouse gene has also been identified. The predicted structure of the protein is a membrane protein with 5 transmembrane domains. We have also expressed a GFP-tagged fusion protein in mouse fibroblasts. Confocal microscopy indicates that this protein is likely to be a novel adhesion molecule, with a cellular distribution characteristic of molecules such as integrins. We aim to determine the function of Ttyh1, its interacting intra- and extra-cellular proteins and to assess its candidature as a molecule of importance in cell migration and adhesion.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
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
Probing JNK MAPK function with peptide inhibitors. It has generally been accepted that the JNK MAPK family of protein kinases is rapidly and potently activated following the exposure of mammalian cells to stresses and cytokines. However, their biological role has remained controversial. We believe that this problem reflects the lack of a generally applicable and specific JNK MAPK inhibitor. In this project we continue our characterisation of a small peptide inhibitor developed in our laboratori ....Probing JNK MAPK function with peptide inhibitors. It has generally been accepted that the JNK MAPK family of protein kinases is rapidly and potently activated following the exposure of mammalian cells to stresses and cytokines. However, their biological role has remained controversial. We believe that this problem reflects the lack of a generally applicable and specific JNK MAPK inhibitor. In this project we continue our characterisation of a small peptide inhibitor developed in our laboratories. We aim to determine its mechanism of inhibition, the specificity of interaction, and to evolve more effective inhibitors. With these new inhibitors, we can effectively address the biological roles of these kinases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560862
Funder
Australian Research Council
Funding Amount
$546,700.00
Summary
South Australian Facility for Advanced Molecular Imaging. The aim of this project is to establish the South Australian Facility for Advanced Molecular Imaging. The Facility builds on existing expertise and cooperation between the collaborating institutions to expand our capability in advanced analytical confocal microscopy of a wide range of materials from living cells to artificial surfaces. New state-of-the-art microscopes will allow the direct quantitative analysis of molecular interactions w ....South Australian Facility for Advanced Molecular Imaging. The aim of this project is to establish the South Australian Facility for Advanced Molecular Imaging. The Facility builds on existing expertise and cooperation between the collaborating institutions to expand our capability in advanced analytical confocal microscopy of a wide range of materials from living cells to artificial surfaces. New state-of-the-art microscopes will allow the direct quantitative analysis of molecular interactions with high temporal and spatial resolutions. This will advance: understanding the regulation of cellular signalling, gene expression and growth in normal and pathological conditions; development of biosensor technology; and the application of new biomaterials in medicine and industry.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less