Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The stud ....Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The study of this transport process will be important for understanding disorders like epilepsy and other disorders affecting neuronal excitability.Read moreRead less
Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of ....Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of novel therapies that promote neuronal regeneration relevant for disorders such as spinal cord injury and Alzheimer's disease, which constitute a large socio-economic burden in Australia. Currently, 400 people contract spinal cord injury every year, corresponding to an annual cost of $1 billion, and more than 500 000 aging people suffer from Alzheimer's disease.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
Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thor ....Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thorough characterisation of a novel pathway that is potentially crucial in the development, homeostasis and regeneration of the nervous system. Disruption of normal function of this system may underlie the hyperexcitability observed in mannu neurodegenerative conditions.Read moreRead less
Glycerotoxin, a unique tool to investigate the dynamic interactions between N-type Ca2+ channels and the exo-endocytic machinery. Communication between neurons relies on exocytosis, a process in which synaptic vesicles containing a neurotransmitter release their content in the extracellular synaptic cleft. We have recently discovered a unique neurotoxin called glycerotoxin (GLTx), which selectively activates Ca2+ channels (Cav2.2), linked with the exocytic machinery in the Central Nervous System ....Glycerotoxin, a unique tool to investigate the dynamic interactions between N-type Ca2+ channels and the exo-endocytic machinery. Communication between neurons relies on exocytosis, a process in which synaptic vesicles containing a neurotransmitter release their content in the extracellular synaptic cleft. We have recently discovered a unique neurotoxin called glycerotoxin (GLTx), which selectively activates Ca2+ channels (Cav2.2), linked with the exocytic machinery in the Central Nervous System. GLTx provide a new tool to further dissect the role of Cav2.2 in controlling neurotransmitter release. GLTx also greatly facilitates synaptic vesicle recycling, suggesting an unexpected link between Cav2.2 activation and the compensatory endocytic machinery. Our goal is to investigate functional coupling between Cav2.2 and the exo- and endocytic machineries using GLTx.Read moreRead less
Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries rises there is an increasing incidence of mental health problems. Therapeutic approaches to both Alzhemier's and Parkinson's disease, as well as to brain injury following stroke, rely on a thorough understanding of how the brain develops. This is consistent with the everyday principle that if you want to fix something that is broken, then you need to understand h ....Assessing gene function in the developing brain using zebrafish as a model system. As the average life expectancy in western countries rises there is an increasing incidence of mental health problems. Therapeutic approaches to both Alzhemier's and Parkinson's disease, as well as to brain injury following stroke, rely on a thorough understanding of how the brain develops. This is consistent with the everyday principle that if you want to fix something that is broken, then you need to understand how it is put together in the first place. This project seeks to understand how the normal brain is wired together in the embryo and, in doing so it will expose novel targets for therapy in the aged.Read moreRead less
Injectable scaffolds for treatments of neurological disorders. Cell replacement therapies offer potentially effective treatments for a host of neurological disorders but a major obstacle confronting their development is to ensure appropriate connections are formed within the brain. This proposal aims to utilize injectable biodegradable polymers, to demonstrate the feasibility of assisting neural cells and stem cells to bridge glial scars or significant distances in the brain and repair damaged n ....Injectable scaffolds for treatments of neurological disorders. Cell replacement therapies offer potentially effective treatments for a host of neurological disorders but a major obstacle confronting their development is to ensure appropriate connections are formed within the brain. This proposal aims to utilize injectable biodegradable polymers, to demonstrate the feasibility of assisting neural cells and stem cells to bridge glial scars or significant distances in the brain and repair damaged neural pathways. This proposal will focus on naturally occurring polysaccharides, which will act as "scaffolds" for the growing neurones. The role the scaffolds play in regulating neurite extension will be investigated in vitro and in vivo.Read moreRead less
Manipulating nano-fibres to control nerve regeneration. Diseases of the brain and mind are the most common diseases in the western world; being even more prevalent than cardiac or malignant disease. With Australia's aging demographic, diseases of the brain and mind will continue to impact on our productivity in the workplace, our quality of life, and the ability of the medicare and private health care systems to keep up with the ever-increasing demand for older Australians.
The research prop ....Manipulating nano-fibres to control nerve regeneration. Diseases of the brain and mind are the most common diseases in the western world; being even more prevalent than cardiac or malignant disease. With Australia's aging demographic, diseases of the brain and mind will continue to impact on our productivity in the workplace, our quality of life, and the ability of the medicare and private health care systems to keep up with the ever-increasing demand for older Australians.
The research proposed here will enable us to find solutions to this serious problem by building on Australia's strong track record in nanotechnology and biotechnology research, and help towards new and effective treatments.
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The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less