Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347955
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
A Cell Sorter Facility for Neuroscience and Related Biotechnology. Neuroscience is entering an era of accelerated discovery in which Queensland neuroscientists can excel if they gain leadership in key technologies. One critical technology is the ability to obtain specific cell populations from various parts of the nervous system in sufficient quantity and purity to enable their accurate examination by gene array, proteomics and physiological techniques. The aim is to establish the world's first ....A Cell Sorter Facility for Neuroscience and Related Biotechnology. Neuroscience is entering an era of accelerated discovery in which Queensland neuroscientists can excel if they gain leadership in key technologies. One critical technology is the ability to obtain specific cell populations from various parts of the nervous system in sufficient quantity and purity to enable their accurate examination by gene array, proteomics and physiological techniques. The aim is to establish the world's first cell-sorting facility dedicated to the production of nerve cells suitable for molecular characterization and screening, providing the basis for identifying key molecules regulating brain function, ageing and repair of great importance to the biotechnology/pharmaceutical industry.Read moreRead less
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Regulation of Stress Hormone Receptors in the Brain. Our research will provide information on how the brain controls our response to stress and will allow the development of targeted strategies to reduce the possibility during chronic stress of the development of conditions such as anxiety and depression. This will improve mental health outcomes in Australia and add to Australia's economic and social stability.
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.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
Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
A mathematical model of calcium signalling in single cells and in multicellular systems. Calcium released from stores inside cells plays a vital signalling role in living organisms. It initiates cell division after fertilization, mediates communication and learning in the nervous system, causes contraction in the muscular walls of arteries and plays an important but as yet poorly understood role in the information processing that occurs in systems of coupled glial cells. We will construct a uni ....A mathematical model of calcium signalling in single cells and in multicellular systems. Calcium released from stores inside cells plays a vital signalling role in living organisms. It initiates cell division after fertilization, mediates communication and learning in the nervous system, causes contraction in the muscular walls of arteries and plays an important but as yet poorly understood role in the information processing that occurs in systems of coupled glial cells. We will construct a unified mathematical model of calcium signalling in multicellular systems, starting from the known processes in single cells, and use it to gain insight into the functioning and possible dysfunctioning of calcium-mediated intercellular communication.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
Hierarchical Phosphorylation of Tyrosine Hydroxylase is Dependent on the Activation Sequence of Signaling Pathways. Protein phosphorylation is a fundamental process in biology. It controls protein expression and function in all cells. Hierarchical phosphorylation is defined as the phosphorylation of a protein at one site leading to an altered phosphorylation at another site on the same protein and an altered biological outcome. We have discovered that the enzyme tyrosine hydroxylase undergoes a ....Hierarchical Phosphorylation of Tyrosine Hydroxylase is Dependent on the Activation Sequence of Signaling Pathways. Protein phosphorylation is a fundamental process in biology. It controls protein expression and function in all cells. Hierarchical phosphorylation is defined as the phosphorylation of a protein at one site leading to an altered phosphorylation at another site on the same protein and an altered biological outcome. We have discovered that the enzyme tyrosine hydroxylase undergoes a form of hierarchical phosphorylation not previously reported. Here we examine hierarchical phosphorylation in rat and human tyrosine hydroxylase and its functional consequence in intact cells. The approaches and methods developed will also be applicable to investigation of hierarchical phosphorylation in other proteins.Read moreRead less
Identifying the specific structural features of metallothionein that regulate its ability to modulate astrogliosis. This project contributes directly to the Designated National Research Priority 2 and could potentially have a significant impact upon the broader Australian Community by identifying a novel and powerful therapeutic agent based upon metallothionein proteins with the ultimate aim of helping patients who have a brain injury or a neurodegenerative disease. It is important to note that ....Identifying the specific structural features of metallothionein that regulate its ability to modulate astrogliosis. This project contributes directly to the Designated National Research Priority 2 and could potentially have a significant impact upon the broader Australian Community by identifying a novel and powerful therapeutic agent based upon metallothionein proteins with the ultimate aim of helping patients who have a brain injury or a neurodegenerative disease. It is important to note that the partnership between UTAS and Bestenbalt LLC is a critical step in the development of these exciting research discoveries into commercially viable outcomes for the Australian Biotechnology Industry and the broader Australian community.Read moreRead less