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
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
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
Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential ground ....Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential groundwork for the development of drugs that target this transport mechanism.Read moreRead less
Visualising neuron-glia interactions in the injured central nervous system. The adult brain and spinal cord recovery poorly from injury. Attempts to overcome this problem include methods to promote the intrinsic regenerative capacity of injured neurons, and modulating the inhibitory extracellular environment to become permissive to regeneration. The goal of this project is to investigate an endogenous regenerative mechanism in the injured brain. This project will use the latest, cutting-edge mic ....Visualising neuron-glia interactions in the injured central nervous system. The adult brain and spinal cord recovery poorly from injury. Attempts to overcome this problem include methods to promote the intrinsic regenerative capacity of injured neurons, and modulating the inhibitory extracellular environment to become permissive to regeneration. The goal of this project is to investigate an endogenous regenerative mechanism in the injured brain. This project will use the latest, cutting-edge microscopy techniques to visualise whether the endogenous astrocyte protein metallothionein can promote regeneration in the injured nervous system of living zebrafish. The successful outcomes of this project will provide significant insight into understanding how the brain responds to injury.Read moreRead less
Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe ....Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe the fundamental process of cell differentiation in the central nervous system.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
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.