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
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
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
Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and w ....Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and whether neurogenesis may be induced by inflammation in the adult. Using transcriptomics we will also determine how the neurogenic environment changes with age/inflammation. This project is an important step in proving that the brain's potential to generate new neurons extends beyond infancy.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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668246
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced Cell Labelling and Imaging Facility. Understanding the genetic regulation of cellular processes such as migration, differentiation and growth is an important frontier technology with significant biomedical potential. The Australian community is facing an increasing need to provide solutions for a variety of human diseases and disorders, including birth defects, nervous system injury and stroke, and ageing-related conditions. The proposed facility will allow researchers to test in vivo g ....Advanced Cell Labelling and Imaging Facility. Understanding the genetic regulation of cellular processes such as migration, differentiation and growth is an important frontier technology with significant biomedical potential. The Australian community is facing an increasing need to provide solutions for a variety of human diseases and disorders, including birth defects, nervous system injury and stroke, and ageing-related conditions. The proposed facility will allow researchers to test in vivo gene/pharmaceutical therapies as well as to better understand the genetic regulation of normal cellular processes. Read moreRead less
Unraveling the role of N-acetyl-aspartate in normal brain function and disease. The purpose of this project is to define the role of the predominating brain chemical N-acetyl-aspartate for normal nerve cell function and as toxic agent causing neurological illness and severe mental health problems. Findings of this research will enhance the design of novel therapies involving pharmacological and genetic treatment.