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.
Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors ....Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors remains unknown. Our project will specifically investigate novel molecular mechanisms associated with serotonin receptor activity that may prove vital in understanding mechanisms of psychiatric illnesses, and how many psychiatric medicines actually work.Read moreRead less
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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453295
Funder
Australian Research Council
Funding Amount
$369,697.00
Summary
NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the ver ....NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the versatility of the USyd. instrument. The installation of a TBI probe at UNSW will counter this, and provide a REAL network of NMR instruments across NSW and the ACT.Read moreRead less
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.