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
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.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
The tau interactome. This project aims to decipher tau-dependent mechanisms at the molecular level to understand its pivotal role in neuronal integrity and function. Tau is a predominantly axonal protein with microtubule stabilising properties and has been implicated in several neurodegenerative disorders, including Alzheimer’s disease. Knowledge of its other physiological roles in the brain is limited, although it seems to be involved in signalling processes. The expected outcome of this study ....The tau interactome. This project aims to decipher tau-dependent mechanisms at the molecular level to understand its pivotal role in neuronal integrity and function. Tau is a predominantly axonal protein with microtubule stabilising properties and has been implicated in several neurodegenerative disorders, including Alzheimer’s disease. Knowledge of its other physiological roles in the brain is limited, although it seems to be involved in signalling processes. The expected outcome of this study is a deeper understanding of brain function during development and aging, which may ultimately contribute to new preventive treatments and medical care strategies.Read moreRead less