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Deciphering The Mechanisms Underlying LRP-mediated Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$370,659.00
Summary
Nerve damage can develop post injury or disease and are often very debilitating, slow to heal and cause increased pain. Our work aims to examine a new class of molecules that we show can activate selected fat-receptors on nerve cells to guide the growth of regenerating nerves. We will determine how these receptors function with the aim of developing a novel class of therapeutics directed at healing nerve damage.
Each year more than one million people in the US alone suffer serious nerve injury significantly impairing quality of life and costing more than US$7 billion. This research will develop nerve conduits based on polymers and the natural constituents of nerve to provide an alternative to the current practice of nerve grafting. It is envisaged that this conduit will provide an effective platform for nerve repair and will expedite the development of regenerative platforms for other neural tissues.
Functional Maturation Of Adult Neural Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$701,390.00
Summary
This proposal seeks to understand how the production of functional nerve cells in the brain is regulated. Specifically we will focus on the way in which adult neuronal precursor cells (neuroblasts) in the brain acquire their functional characteristics as they mature into active entities capable of forming neural networks. We will examine the expression and activation of specific membrane proteins (ion channels) on the differentiation and migration of neuronal precursor cells.
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.
Defective Repair Of Neuronal Activity-induced DNA Double Strand Breaks: A Novel Pathogenic Mechanism For Neurodegeneration In Ataxia-telangiectasia
Funder
National Health and Medical Research Council
Funding Amount
$570,821.00
Summary
The reason for degeneration of the hindbrain in patients with Ataxia-telangiectasia is unknown. Firing of neurons leads to breaks in the DNA that are normally repaired by ATM, the gene defective in Ataxia-telangiectasia, and failure to reset the system likely leads to abnormal gene expression and cell death. Here we use neuronal cell types derived from patient stem cells to elucidate how this novel disease mechanism may cause hindbrain degeneration and to test drugs that can overcome this.
Cell-based Neurotrophin Delivery With Cochlear Implantation For Long-term Rescue Of Auditory Neurones Following Deafness
Funder
National Health and Medical Research Council
Funding Amount
$437,212.00
Summary
This project aims to develop safe and effective techniques for long-term delivery of drugs to the ear by genetically modifying cells so they release the theraputic agents over extended periods of time, and then to use encapsulation techniques to safely deliver these cells to the inner ear in combination with a cochlear implant.
Cellular Mechanisms Underlying Neurodegenerative Disease And The Neuronal Response To Trauma
Funder
National Health and Medical Research Council
Funding Amount
$406,264.00
Summary
Brain and spinal cord injury are major causes of death and disability, with degenerative diseases similarly affecting large proportions of the population. The singular objective of my research proposal is to increase our understanding of the molecular and cellular processes by which nerve cells respond to trauma and diseases such as Alzheimer’s and Parkinson’s, and to identify new therapeutic approaches aimed at encouraging the repair of damaged cells.
Development of normal brain function requires information transfer and integration from outside and within the brain. Normal brain wiring is guided by genetic and environmental cues, whose relative contributions remain controversial. This project investigates the physiological and behavioural consequences of abnormal brain wiring, and the potential for controlled environments and targeted interventions to overcome the deficits. Relevance includes neurotrauma as well as mental illnesses.
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