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
Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying ....Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying treatments are developed. This research program will provide novel realistic pharmaceutical approaches to treat AD. Even if the onset of AD could be delayed by a few years the personal and financial benefits would be enormous. The potential for this research to generate commercially viable Australian intellectual property is also significant.Read moreRead less
The role of LIM Kinase 1 in neurons. The aim of this project is to study LIM domain kinase 1 in neuronal function, using cell and mouse models. Unrestricted brain function is essential to one’s wellbeing and the ability to perform normally. Critically contributing to the function of neurons is a cytoskeleton which maintains morphology and function. However, molecular mechanisms underlying cytoskeletal dynamics are poorly understood. LIM domain kinase 1, a key regulator of the actin cytoskeleton ....The role of LIM Kinase 1 in neurons. The aim of this project is to study LIM domain kinase 1 in neuronal function, using cell and mouse models. Unrestricted brain function is essential to one’s wellbeing and the ability to perform normally. Critically contributing to the function of neurons is a cytoskeleton which maintains morphology and function. However, molecular mechanisms underlying cytoskeletal dynamics are poorly understood. LIM domain kinase 1, a key regulator of the actin cytoskeleton decreased with age and its loss associated with deficits in memory and neuronal morphology. This project could reveal fundamental processes regulating and maintaining brain function.Read moreRead less
Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) wi ....Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) will be followed directly by assay development for tau-directed drug screening. The national benefit of this research is manifold by (a) patenting new data, (b) developing treatment strategies for an un-curable disease, and (c) establishing links to the growing Australian biotech industry (in addition to existing links to international pharmaceutical companies).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
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
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.