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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
Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are c ....Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are controlled, which is vital for developing better treatments for neurological disorders such as stroke. The project will also provide research training in experimental/computational molecular biology, which is a rapidly growing field underpinning the biotechnological and pharmaceutical industries. 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
Using metallothioneins as a model for understanding cellular and biochemical interactions between neurons and astrocytes within the brain. This research will reveal some of the changes that occur in the relationship between neurons and astrocytes as a consequence injury, aging or disease to the human brain. In national terms, it will contribute to the concerted effort by Australian scientists to understand how and why neurons die following brain injury or in neurodegenerative diseases. These a ....Using metallothioneins as a model for understanding cellular and biochemical interactions between neurons and astrocytes within the brain. This research will reveal some of the changes that occur in the relationship between neurons and astrocytes as a consequence injury, aging or disease to the human brain. In national terms, it will contribute to the concerted effort by Australian scientists to understand how and why neurons die following brain injury or in neurodegenerative diseases. These are significant community issues in both economical and social terms. Furthermore, this research contributes directly to the Designated National Research Priorities by identifying some of the earliest cellular processes associated with aging or disease of the brain, and will provide clues to promoting healthy aging.Read moreRead less
Redefining the metallothionein's role in the injured brain: extracellular metallothioneins play an important role in astrocyte-neuron responses to injury. This project is being performed by an Australian team of researchers who are leaders in this field of research, and has significant national benefits in supporting this team reveal fundamental information on the cellular interactions that occur between astrocytes and neurons within the injured brain. In national terms, it will contribute to th ....Redefining the metallothionein's role in the injured brain: extracellular metallothioneins play an important role in astrocyte-neuron responses to injury. This project is being performed by an Australian team of researchers who are leaders in this field of research, and has significant national benefits in supporting this team reveal fundamental information on the cellular interactions that occur between astrocytes and neurons within the injured brain. In national terms, it will contribute to the concerted effort by Australian scientists to understand how and why neurons die following brain injury or neurodegenerative disease. Furthermore, this research contributes directly to the Designated National Research Priorities by identifying some of the earliest biochemical and cellular processes associated with aging or disease of the brain.Read moreRead less
Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers ....Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers G protein-coupling to the intracellular portion of the GABA-BR2 subunit. Focus will be on different modes of GPCR signalling, including constitutive activity and roles for membrane and cytosolic regulatory proteins. Targeted studies of GABAB receptor subunits will provide new information on the mechanistic regulation of GPCR signalling.Read moreRead less
Understanding the changes in brain chemistry associated with schizophrenia. Current drugs for schizophrenia only work in 30% of patients. To develop better therapies, we must understand the changes in the brains of people with the disorder. This research will explore a chemical system in the brain that is changed in schizophrenia and begin to investigate whether counteracting these changes are therapeutically beneficial.
LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor n ....LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor neuron development interact with each other and with DNA. With this information we are developing reagents that can be used to further probe central nervous system function and may ultimately be used to regenerate damaged nerves.Read moreRead less
The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciph ....The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciphering basic biological mechanisms, patenting new data, developing treatment strategies for un-curable and fatal disorders, and expanding links to Australian biotech and international pharmaceutical companies.Read moreRead less
Neuronal functions of the microtubule-associated protein tau in development and ageing. The project uses a combination of transgenic mouse strains characterised by neurodegeneration and senescence-accelerated (SAM) mice, to determine the first steps of the aggregation of the protein tau in degenerating neurons, how absence of tau protects from brain atrophy, and in which physiological processes tau is involved. This project provides the biological foundation for a tau-based therapy of senescence ....Neuronal functions of the microtubule-associated protein tau in development and ageing. The project uses a combination of transgenic mouse strains characterised by neurodegeneration and senescence-accelerated (SAM) mice, to determine the first steps of the aggregation of the protein tau in degenerating neurons, how absence of tau protects from brain atrophy, and in which physiological processes tau is involved. This project provides the biological foundation for a tau-based therapy of senescence-associated conditions. It provides the biological foundation for developing effective therapies for human neurodegenerative conditions, by preventing tau aggregation and phosphorylation. We will patent new data and expand our existing links to Australian biotech and international pharmaceutical companies.Read moreRead less