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Membrane Fusion In Axonal Regeneration: Molecules And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Limited nerve regeneration is the main obstacle for recovery from spinal cord and brain injuries. Understanding the cellular and molecular mechanisms underlying axonal regeneration is an essential step toward the development of novel effective therapies to enhance this process. In this proposal, we use the powerful molecular and genetic tools available for the small nematode worm C. elegans to identify and study axonal regeneration and discover the key molecules involved.
Axonal Regeneration And Degeneration: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Understanding how to repair of nerve damage following a traumatic injury, a vascular accident, or a degenerative condition, is essential to develop novel effective treatments. We have identified, in a simple genetic model system, the molecular mechanisms that allow a transected nerve to be repaired by reattachment of its two separated fragments. This 'axonal fusion' process is a highly promising innovative approach that can be exploited to restore the original neuronal circuit.
I am a neuroscientist using robust statistical methods to identify effective neuroprotectants for stroke. I am examining the use of neuroprotection and novel imaging approaches to extend the utility of thrombolysis, and testing the hypothesis that neuropr
Validating Novel Serum Markers Of Neurodegeneration In Multiple Sclerosis Patients.
Funder
National Health and Medical Research Council
Funding Amount
$516,304.00
Summary
In multiple sclerosis (MS), permanent disability occurs when brain cells known as neurons are damaged following an immune attack. Current treatments reduce the number and severity of immune attacks, but they do not prevent neuron damage or permanent disability in many patients. There is currently no direct way to measure neuron damage in humans, so it is difficult to develop new drugs to prevent it. To address this need, we will trial a new blood test for measuring neuron damage in MS patients.
Signalling Mechanisms Regulating Neurogenesis And Neurite Outgrowth
Funder
National Health and Medical Research Council
Funding Amount
$486,000.00
Summary
Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emer ....Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emerged in recent years, that has led to the view that repair of the central nervous system following injury of disease may indeed be a possibility. Effective neural repair is likely to require a multi-factorial approach, including blockage of neuronal death, replacement of lost neurons by neural stem cells, and regulation of appropriate subsequent neurite outgrowth and formation of correct connections. We have shown that a regulator of cytokine signaling, SOCS2, promotes neuronal differentiation and neurite outgrowth. This project aims to continue our investigations of the role of SOCS2 and interacting factors in regulating neuronal differentiation as well as substantially expanding our investigations into the role of SOCS2 in regulating neurite outgrowth, using both in vitro and in vivo models. An understanding of the mechanisms involved in these processes may allow us to derive therapies for the repair of the nervous system after injury or disease.Read moreRead less
Therapeutic Development Of A Novel EphA4 Antagonist For Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$687,105.00
Summary
Spinal cord injuries impose a significant burden on patients and their carers. At present, there are no treatments for spinal cord injury that provide functional improvement. This research program will develop a novel therapeutic molecule, EphA4-Fc, which promotes axonal regeneration and delivers significant functional improvement. We will determine the most effective protocol for EphA4-Fc administration and the physiological and functional outcomes of these treatment regimes.
Cellular And Molecular Mechanisms Of Development And Regeneration In The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$345,773.00
Summary
During development of the fetal brain, cells are wired together. The correct wiring patterns are essential for normal function of the brain. Growth and formation of new connections decreases after birth. For this reason, the repair of the damaged adult nervous system is limited. However, there is one region in the nervous system that exhibits continual growth and repair throughout life. This is the nerve that is responsible for smell and connects the nose to the brain. The aim of this study is t ....During development of the fetal brain, cells are wired together. The correct wiring patterns are essential for normal function of the brain. Growth and formation of new connections decreases after birth. For this reason, the repair of the damaged adult nervous system is limited. However, there is one region in the nervous system that exhibits continual growth and repair throughout life. This is the nerve that is responsible for smell and connects the nose to the brain. The aim of this study is to identify the processes that permit continual growth within this region of the nervous system.Read moreRead less
The Role Of Membrane Phospholipids In Regenerative Axonal Fusion
Funder
National Health and Medical Research Council
Funding Amount
$571,950.00
Summary
Injuries to the nervous system can cause lifelong disabilities due to ineffective repair of the damaged nerve fibres. Our previous research has identified a highly efficient mechanism that occurs in nematode worms that allows severed nerves to fuse back together. We will now focus on understanding precisely how this mechanism works, and investigate its utility in repairing nerves that don’t normally utilise this repair mechanism.
Connectivity Of Regenerating Axons Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Our objective is to thoroughly investigate the connections made by regenerating nerve fibres in mice which are treated with specific compounds to inhibit scarring as well as with active exercise following spinal cord injury. This will provide evidence of the potential of these compounds as a therapeutic intervention. Understanding how the nervous system rewires following exercise intervention will provide insights as to how new connections can be shaped to ensure optimal recovery of function.
Determination Of Sympathetic Preganglionic Neuronal Phenotype
Funder
National Health and Medical Research Council
Funding Amount
$241,527.00
Summary
The nervous system is the single most complex part of our body. Its function depends on millions of connections between neurons, all of which must form correctly during development. Furthermore, each neuron must select a neurotransmitter with which to talk to its target neuron. A neurotransmitter is a chemical released from a neuron, which passes a signal to a target cell. Some neurotransmitters cause excitation of the target cell, others inhibition. Each neurotransmitter signals to the target c ....The nervous system is the single most complex part of our body. Its function depends on millions of connections between neurons, all of which must form correctly during development. Furthermore, each neuron must select a neurotransmitter with which to talk to its target neuron. A neurotransmitter is a chemical released from a neuron, which passes a signal to a target cell. Some neurotransmitters cause excitation of the target cell, others inhibition. Each neurotransmitter signals to the target cell via receptor molecule, matched to the neurotransmitter. Thus, a neuron is faced not only with making choices about what connections to make within the developing brain, but also it must select from a range of potential neurotransmitters and receptor molecules. We are interested in how neurons select the appropriate neurotransmitter. There are a number of ways that a neuron might be guided to the correct choice. It is possible that it could receive from the target cell a signal that guides the choice of neurotransmitter. We wish to examine this hypothesis to see if it is applicable to the autonomic nervous system, that part of the nervous system that controls functions like changes in blood pressure and heart rate. Our laboratory is expert in identifying the chemistry of autonomic neurons. We will use this knowledge to see what happens when we deliberately perturb the normal connections of autonomic neurons. Do they persist in expressing the neurotransmitters they would have done prior to the perturbation? Alternatively, do they adapt to the change of target via a signal received from the new target cell and express the appropriate phenotype? The results of these experiments will give insights into how the brain develops. The results will be important for both our basic understanding of biology and as a basis for the development of techniques for reversing neuronal damage.Read moreRead less