An X-ray crystallographic investigation into co-receptors on T-lymphocytes. T lymphocytes are an indispensable cellular component of the immune system. The normal process of T cell selection in the thymus, and the ability of mature T cells to respond to foreign antigens are governed by receptor recognition and co-receptor mediated events. The co-receptors encompass a wide spectrum of structurally diverse proteins that are involved in adhesion, co-ligation and signal transduction. This proposa ....An X-ray crystallographic investigation into co-receptors on T-lymphocytes. T lymphocytes are an indispensable cellular component of the immune system. The normal process of T cell selection in the thymus, and the ability of mature T cells to respond to foreign antigens are governed by receptor recognition and co-receptor mediated events. The co-receptors encompass a wide spectrum of structurally diverse proteins that are involved in adhesion, co-ligation and signal transduction. This proposal aims to investigate, using X-ray crystallography as the primary research tool, co- receptors located on T-lymphocytes. This work will gain fundamental insights into co-receptor function.Read moreRead less
Insertion and assembly of proteins and lipids into biological membranes. We propose a multi-disciplinary approach to this fundamental biological problem and have established collaborations with experts in the USA, UK and Austria. Benefits from this research program fall into two discrete types. Firstly, detailed knowledge of the mechanism what is now a poorly understood biological process of cellular membrane assembly, with the prospects for using the knowledge for intervention into diseases suc ....Insertion and assembly of proteins and lipids into biological membranes. We propose a multi-disciplinary approach to this fundamental biological problem and have established collaborations with experts in the USA, UK and Austria. Benefits from this research program fall into two discrete types. Firstly, detailed knowledge of the mechanism what is now a poorly understood biological process of cellular membrane assembly, with the prospects for using the knowledge for intervention into diseases such as cancer. Secondly, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the development of skills not common in Australia.Read moreRead less
Delineating the role of the GxxxG motif in transmembrane protein metabolism. This study will define how a well defined motif involved in transmembrane interactions affects the metabolism of proteins. Since this motif is present in proteins involved in Alzheimer's disease it has potential benefits for community health and combating ageing.
Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoin ....Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoing and healthy association at the cellular level. Unlike some terrestrial symbioses, little is known about the structure and function of the coral symbiosome. This study sets out to investigate this membrane at the cellular and molecular level.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
Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the ....Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the host's immune system will also be gained. The techniques established during the study of MSP-2 will be useful for the study of larger proteins and protein complexes from many systems in the future.Read moreRead less
Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. Th ....Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. The outcome has the potential to vastly improve prospects for up to 200,000 Australians. Intellectual property (IP) retained in Australia will generate future biotechnology industry. The novel chemical biological approaches will facilitate training of future generations of Australian scientists.Read moreRead less
Molecular basis of the antimicrobial activity of the floral defensin, NaD1, for the plant pathogen Fusarium oxysporum. Filamentous fungi are responsible for many major plant diseases that result in devastating crop losses and food spoilage world wide. Currently there are no resistant cultivars or adequate chemical controls for many of these diseases. The plant defensin, NaD1, stops the growth of many pathogens, including the recalcitrant fungi Fusarium oxysporum and Botrytis cinerea, and has bee ....Molecular basis of the antimicrobial activity of the floral defensin, NaD1, for the plant pathogen Fusarium oxysporum. Filamentous fungi are responsible for many major plant diseases that result in devastating crop losses and food spoilage world wide. Currently there are no resistant cultivars or adequate chemical controls for many of these diseases. The plant defensin, NaD1, stops the growth of many pathogens, including the recalcitrant fungi Fusarium oxysporum and Botrytis cinerea, and has been shown to protect transgenic cotton against fungal infection in glasshouse and field trials. NaD1 has potential application for durable, broad spectrum fungal disease control in crops. This will lead to both environmental and economic benefits to Australia. Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less