Eruption dynamics and tsunami potential from submarine volcanoes. This project is based on recently acquired seafloor samples and geophysical data from extraordinary deposits at a modern submarine volcano. This project aims to determine the conditions that lead to explosive eruption underwater, the dynamics of associated sediment flows, and if these events can trigger tsunami. Expected outcomes include an unprecedented reconstruction of the architecture of submarine caldera volcanoes, new innova ....Eruption dynamics and tsunami potential from submarine volcanoes. This project is based on recently acquired seafloor samples and geophysical data from extraordinary deposits at a modern submarine volcano. This project aims to determine the conditions that lead to explosive eruption underwater, the dynamics of associated sediment flows, and if these events can trigger tsunami. Expected outcomes include an unprecedented reconstruction of the architecture of submarine caldera volcanoes, new innovative models applicable globally for a richer understanding of volcanic tsunami and eruptions that shape the seafloor. This project will provide significant benefits through mitigation of global marine natural hazards, and by improving knowledge on the volcanic hosts of ore deposits.Read moreRead less
A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of ele ....Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of electrophysiology and molecular biology we expect to learn the fundamental mechanisms that modulate the opening and closing of store-operated calcium channels and to gain an important information that can be used for determining the molecular structure of these channelsRead moreRead less
Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential ....Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential-1 (TRP-1) protein in hepatocytes. The electrophysiological properties, mechanisms of activation and intracellular trafficking of the channels will be investigated. It is anticipated the results will provide basic information on the physiological functions of second messenger-activated calcium channels. This will benefit the understanding of liver function, hepatotoxicity in animals, animal production and the development of pharmaceuticals in animal husbandary.Read moreRead less
The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progress ....The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progression. The work will contribute to the training of one or more graduate students in a technologically advancing and internationally competitive field.Read moreRead less
Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.
Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and ....Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and in vivo, we will be able to define the molecular changes in neurites that control neurite branching. This should provide significant benefits, such as gaining crucial insights into the mechanisms of forming complex neuronal networks.Read moreRead less
Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to un ....Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to understand how actinin-4, a component of the actin cytoskeleton in non-muscle tissues, interacts with and is stimulated by proteins of the intracellular signalling cascade.Read moreRead less
Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where ....Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where DNA beta enhances virus replication and disease severity. DNA beta has the potential to enter Australia with several different geminiviruses and to spread into others by co-infection, which requires research on detection and pathogenesis of DNA beta.Read moreRead less
Non-classical steroid signalling through SF-1 responsive genes: a key mechanism in environmental endocrine disruption, cancer, and aging. Endocrine disruption by pervasive manmade chemicals, which mimic natural hormones, and are found in plastics, cosmetics, and fire retardants, is known to cause developmental defects in model organisms and wildlife, with substantial risk also to human health. This risk increases with increasing population density and dependence on water recycling. Current tests ....Non-classical steroid signalling through SF-1 responsive genes: a key mechanism in environmental endocrine disruption, cancer, and aging. Endocrine disruption by pervasive manmade chemicals, which mimic natural hormones, and are found in plastics, cosmetics, and fire retardants, is known to cause developmental defects in model organisms and wildlife, with substantial risk also to human health. This risk increases with increasing population density and dependence on water recycling. Current tests to assess such substances use oversimplified modes of hormone action and grossly underestimate the risk of endocrine disruption. This proposal will yield new knowledge about how such substances act in the body, or on wildlife, and form the basis for new more sensitive methods of environmental monitoring.Read moreRead less