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Protein Partners Of Rapsyn That Regulate Acetylcholine Receptor Clustering
Funder
National Health and Medical Research Council
Funding Amount
$411,000.00
Summary
Spinal nerves control our limb muscles by releasing chemical signals directly onto the surface of muscle fibres that they contact. These chemical signalling contacts are called synapses. They are like the synapses between nerve cells in our brains but easier to study, meaning that we can make more rapid progress in understanding how synapses work. The sensor receptors for chemical signals at the nerve-to-muscle synapse are held in place on the muscle fibre surface by a protein called rapsyn. In ....Spinal nerves control our limb muscles by releasing chemical signals directly onto the surface of muscle fibres that they contact. These chemical signalling contacts are called synapses. They are like the synapses between nerve cells in our brains but easier to study, meaning that we can make more rapid progress in understanding how synapses work. The sensor receptors for chemical signals at the nerve-to-muscle synapse are held in place on the muscle fibre surface by a protein called rapsyn. In turn, rapsyn must be organized by other chemical signals from the nerve, but we don't know exactly how this happens. When the receptors become disorganized at the synapse, in diseases such as Myasthenia Gravis, we lose control of our muscles. This project will employ newly developing techniques of proteomics and genomics to identify new proteins that bind to rapsyn and to test how they work to organize receptors at the synapse. By identifying the proteins that control rapsyn we may be able to develop new treatments for Myasthenia Gravis that restore the function of the synapse with less side effects than current therapies.Read moreRead less
Postsynaptic Signalling Systems That Sustain The Nerve-muscle Synapse
Funder
National Health and Medical Research Council
Funding Amount
$598,041.00
Summary
Neuromuscular junctions (NMJ) are the synapses through which motor nerves control our voluntary muscle cells. This project will investigate the molecular signalling system between nerve and muscle that helps maintain healthy NMJs. Normal ageing involves a progressive decline in muscle strength, often leading to loss of independence in the elderly. We will use a mouse model to test whether a breakdown of the NMJ signalling system contributes to the loss of strength in old age.
NEU-HORIZONS: The Neuroprotection And Therapeutic Use Of Riluzole For The Prevention Of Oxaliplatin Neurotoxicity Study.
Funder
National Health and Medical Research Council
Funding Amount
$382,402.00
Summary
Colorectal cancer is the second most commonly diagnosed cancer in Australia, with more than 13500 cases recorded annually. Oxaliplatin is an effective chemotherapy for the treatment of colorectal cancer. The major side-effect of oxaliplatin is the development of nerve damage that leads to loss of feeling in the hands and feet and significant disability. The aim of this study is to conduct a trial of a new treatment for oxaliplatin-induced nerve damage.
Role Of Synaptogenesis In Developmental Motoneuron Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$361,650.00
Summary
Naturally occurring cell death is an important and necessary event that shapes the developing embryo. It occurs in all organs of the developing body. In the nervous system about 50% of all neurons die at a time when they are making contact with one another or with their target organs. The underlying mechanisms that drive programmed neuronal cell death are not known. One possibility is that the formation of neuronal contacts (synapses) with other neurons and target cells determines the fate of a ....Naturally occurring cell death is an important and necessary event that shapes the developing embryo. It occurs in all organs of the developing body. In the nervous system about 50% of all neurons die at a time when they are making contact with one another or with their target organs. The underlying mechanisms that drive programmed neuronal cell death are not known. One possibility is that the formation of neuronal contacts (synapses) with other neurons and target cells determines the fate of a neuron. The connections of motor neurons with muscle during this period of developmental neuronal cell death is the best model to examine this phenomenon. In this grant we are in an exciting position to be able to address what causes neuronal cell death, as we have a number of mice that lack key molecules needed for the formation of specializations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motor neurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motor neurons' fate is determined during the period of programmed cell death. The outcomes of this research will enable us to understand how the nervous system is shaped during development and will increase our knowledge about the basis of adult neurodegenerative diseases. For example, the pathology of Alzheimer's is characterised by a breakdown in neuronal connections that ultimately result in neuronal death and a loss of thought processes (cognition).Read moreRead less
The Role Of Endogenous Glucocorticoids In Autoimmune Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$693,185.00
Summary
Inflammatory joint diseases affect millions of people worldwide and in most patients these often chronic conditions can not be cured. In an experimental model of arthritis we have found that bone cells can modify the severity of inflammation when certain hormonal signals are blocked. This study will identify the mechanisms underlying these hormonal effects with the aim to find new targets for efficient treatments for arthritis.