Pathogenic And Adaptive Molecular Interactions With Mutant Huntingtin Exon 1
Funder
National Health and Medical Research Council
Funding Amount
$727,117.00
Summary
This project aims to determine how the gene mutation that causes Huntington’s disease (HD) damages cells in the brain. The diseased gene creates a protein that is abnormally sticky, which causes it to form clumps. Our goal is to determine the components of the cell that are disrupted and damaged as clumping happens. Understanding this link will enable therapeutics to be logically designed in efforts to prevent harm to the brain, potentially before symptoms are evident.
The Role Of Copper In Ubiquitin-dependent Protein Degradation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
Ubiquitin’s are small proteins that tag other proteins in a process known as “Ubiquitination”. Often this is to target them for degradation once they are no longer needed i.e. to take out the rubbish. This process is disrupted in Alzheimer’s disease (AD), which may contribute to the disease. This project aims to find out if copper, an essential metal for life, is required for this process. Drugs that are designed to deliver copper to brain cells have been effective in small AD clinical trials.
Regulation Of Synaptic Vesicle Biogenesis For Synaptic Transmission
Funder
National Health and Medical Research Council
Funding Amount
$339,115.00
Summary
The overall aim is to better understand the molecular processes of nerve cell communication during learning, memory and abnormal brain activity that cause neurological diseases. The supply and generation (biogenesis) of synaptic vesicles (SVs) in nerve cells is critical to sustain neurotransmission. It requires complex protein interactions and signalling. Thus modulation of SV biogenesis at the molecular level will allows future development of new targeted treatments for neurological diseases.
Neurons are highly compartmentalized cell-types. In neurodegenerative diseases such as Alzheimer's disease, the protein Tau that serves a distinct function in one cellular compartment (the axon) accumulates in a massively phosphorylated form elsewhere (somatodendritic compartments and their spines) which is believed to impair neuronal functions. We will investigate how Tau is distributed in health and disease, and determine how this distribution is regulated.
Cellular Pathogenesis Of Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$124,530.00
Summary
Alzheimer's disease is the most common neurodegenerative disease of the ageing population and is associated with toxicity of the Abeta peptide. Prion diseases (eg CJD in humans) are infectious neurodegenerative disorders caused by misfolding of the prion protein. This proposal aims to bring together similar features of these diseases using novel cell and animal based studies to develop better diagnostics and greater understanding of the molecular basis of these disorders with a view to developin ....Alzheimer's disease is the most common neurodegenerative disease of the ageing population and is associated with toxicity of the Abeta peptide. Prion diseases (eg CJD in humans) are infectious neurodegenerative disorders caused by misfolding of the prion protein. This proposal aims to bring together similar features of these diseases using novel cell and animal based studies to develop better diagnostics and greater understanding of the molecular basis of these disorders with a view to developing interventional therapies.Read moreRead less
Protein Phosphatase 2A Methylation: Regulation And Functional Significance For Tauopathies
Funder
National Health and Medical Research Council
Funding Amount
$470,713.00
Summary
Clinical studies have revealed that low blood levels of the vitamin folate are a risk factor for cognitive impairment, depression and dementia, which are prevalent in the elderly. Deregulation of the protein tau is a key event in Alzheimer’s disease pathogenesis. This project will utilize cell culture and aged mouse models to determine how alterations in folate status and deregulation of protein phosphatase 2A affect the regulation of tau and other key brain processes that become altered in Alzh ....Clinical studies have revealed that low blood levels of the vitamin folate are a risk factor for cognitive impairment, depression and dementia, which are prevalent in the elderly. Deregulation of the protein tau is a key event in Alzheimer’s disease pathogenesis. This project will utilize cell culture and aged mouse models to determine how alterations in folate status and deregulation of protein phosphatase 2A affect the regulation of tau and other key brain processes that become altered in Alzheimer’s disease.Read moreRead less
How Alzheimers-associated Cytoskeletal Inclusions Form Road Blocks And Impair Trafficking In Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,181.00
Summary
This research is aimed at delineating basic mechanisms of nerve cell dysfunction relevant to Alzheimer's disease and other dementias with the goal of achieving a positive impact into understanding the causes of these diseases. The outcomes of the project will identify pathways involved in generating pathological changes in nerve cells and will therefore facilitate the development of targeted therapies, ultimately improving the outlook for Alzheimer's patients and the community.
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
Mechanisms Of Glutamate Receptor Maturation In Chicken Brain
Funder
National Health and Medical Research Council
Funding Amount
$418,980.00
Summary
In the brain, many key proteins involved in signalling change during development as part of the fine tuning of the network of connections between nerve cells. Disorders of this fine tuning are thought to result in a number of neurological or psychiatric conditions such as epilepsy and schizophrenia. This project will investigate the maturation of signalling molecules in the brain (receptors for the neurotransmitter glutamate, key enzymes called protein kinases and protein phosphatases that contr ....In the brain, many key proteins involved in signalling change during development as part of the fine tuning of the network of connections between nerve cells. Disorders of this fine tuning are thought to result in a number of neurological or psychiatric conditions such as epilepsy and schizophrenia. This project will investigate the maturation of signalling molecules in the brain (receptors for the neurotransmitter glutamate, key enzymes called protein kinases and protein phosphatases that control the activity of receptors and scaffolding proteins that bind the whole lot into a signalling complex). The project uses chickens as a novel animal model because chicken brain has a slow maturation that occurs well after the initial wiring of the brain is complete. This enables the maturation changes to be clearly identified and experimentally modified. The project combines investigations at the molecular, physiological and behavioural levels. The effects of hormones and drugs on maturation will be investigated. Because brain maturation in humans is also slow an understanding of the way in which this maturation is controlled may provide insights into what causes some neurological-psychiatric disorders in children and adolescents and how to treat or prevent them.Read moreRead less