The Use Of Soluble Antagonists Of EphA4 In Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$622,361.00
Summary
Permanent and limited recovery of function following spinal cord injury is a direct result of the lack of nerve regrowth through the injury. Our preliminary data suggest that antagonising the effects of EphA4, a protein involved in brain development, leads to substantial functional recovery simultaneous with nerve regrowth. In addition to designing new, more effective blockers of EphA4, we will study the signalling pathways that EphA4 activates to inhibit nerve regrowth.
The Role Of PIPP In Cell Polarization And Proliferation.
Funder
National Health and Medical Research Council
Funding Amount
$533,828.00
Summary
Normally cells only divide when they receive a stimulus such as from a hormone or growth factor. Upon stimulation, a series of signals are generated inside the cell which lead to cell division and development. One of the signaling pathways which responds to growth factor stimulation is the PI3-kinase pathway. This pathway has been implicated in many different human cancers which occur when cells divide uncontrollably and invade into the surrounding tissues. Following growth factor stimulation, P ....Normally cells only divide when they receive a stimulus such as from a hormone or growth factor. Upon stimulation, a series of signals are generated inside the cell which lead to cell division and development. One of the signaling pathways which responds to growth factor stimulation is the PI3-kinase pathway. This pathway has been implicated in many different human cancers which occur when cells divide uncontrollably and invade into the surrounding tissues. Following growth factor stimulation, PI3-kinase generates a molecule known as PtdIns(3,4,5)P3 which leads to the activation of many proteins in the signaling pathway. All cells which have PI3-kinase also have enzymes which act to switch off the signals generated by PI3-kinase and thus may play a role in preventing cancer and regulating cell development. We have identified a new enzyme known as PIPP and have shown that it acts to switch off the signals generated by PI3-kinase. We plan to investigate the role of PIPP by increasing or decreasing the amount of PIPP in cells and analysing the effects on cell growth and development. We have also identified a number of proteins which bind to PIPP and we will investigate the role these proteins play in regulating cell signaling. In addition, we plan to characterize the function of PIPP in a whole animal by generating mice which lack PIPP (knockout mice) and assessing the effects on development and cancer.Read moreRead less
Targetting Nogo A As A Means To Promote CNS Axonal Regrowth
Funder
National Health and Medical Research Council
Funding Amount
$325,911.00
Summary
Unlike the peripheral nervous system, regenerative nerve fiber growth and structural plasticity are limited in the adult mammalian central nervous system (CNS), following injury. Although lesioned axons can sprout spontaneously, this regeneration attempt is transitory and no significant re-growth occurs over long distances. Consequently, injury to the CNS often leads to permanent disability. In many cases, it has been shown that it is not the absence of growth-promoting molecules in the CNS but ....Unlike the peripheral nervous system, regenerative nerve fiber growth and structural plasticity are limited in the adult mammalian central nervous system (CNS), following injury. Although lesioned axons can sprout spontaneously, this regeneration attempt is transitory and no significant re-growth occurs over long distances. Consequently, injury to the CNS often leads to permanent disability. In many cases, it has been shown that it is not the absence of growth-promoting molecules in the CNS but rather the presence of axon outgrowth inhibitors, including components of both CNS myelin and astroglial scars that limit regeneration. Given that axonal injury is an important pathological determinant of permanent disability in multiple sclerosis (MS), we have recently investigated the role of the CNS neurite outgrowth inhibitor, Nogo A in the development of a chronic form of murine MS-like disease. We showed that targeting Nogo A by active and passive immunization blunts clinical signs, demyelination and axonal damage associated with this model of MS. These results identify Nogo A as an important determinant of the development of autoimmune-mediated demyelination and suggest that its blockage may help to maintain and-or to restore the neuronal integrity of the CNS after autoimmune insult in disease such as MS. The principal goal of this application is to study the mechanism by which blockade of Nogo A improves clinical outcome in disease like MS and to determine whether neurite sprouting accounts for such an improvement. Targeting Nogo A and-or its receptor, has the potential to not only regulate-modulate the process of autoimmune mediated demyelination but could lead to the first therapy ever offered to patients that helps damaged nerves regenerate after axonal injury following neurodegeneration due to insult or disease.Read moreRead less
A Wireless Electric Nerve-guide For Peripheral Nerve Repair
Funder
National Health and Medical Research Council
Funding Amount
$805,064.00
Summary
We aim to deliver a radical new precision intervention for peripheral nerve repair to improve the lives of people with peripheral nerve damage. Drawing from our recently awarded work on 'electric neural tissue engineering', we will pre-clinically test our invention of a unique clinically-amenable electric nerve-guide (e-nerve-guide), designed to act as a protective nerve conduit and wirelessly electrically-stimulate damaged nerves for their regeneration and restoration of function.
Computational Analysis Of The Influence Of Growth Cone Shape Dynamics On Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$346,406.00
Summary
For the brain to function correctly its neurons must be connected correctly. This project will use a novel mathematical approach to understand how growing nerve fibres find where to go in the developing brain. In particular we will use both experiments and computational analysis to understand how the shape of the tip of a growing nerve fibre helps the fibre navigate. This may help us understand the biological cause of many different types of mental disorders.
Lipid Rafts, Amyloid Neurotoxicity And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Alzheimer's disease is the major cause of dementia in the elderly. Individuals with Alzheimer's disease exhibit a slow decline in cognition which usually results in prolonged institutionalisation. This creates an enormous burden on society. The project aims to identify mechanisms which cause Alzheimer's disease. Specifically, it will examine how a component of the brain, known as the amyloid protein, contributes to nerve cell degeneration. It is hoped that by identifying these mechanisms, new ta ....Alzheimer's disease is the major cause of dementia in the elderly. Individuals with Alzheimer's disease exhibit a slow decline in cognition which usually results in prolonged institutionalisation. This creates an enormous burden on society. The project aims to identify mechanisms which cause Alzheimer's disease. Specifically, it will examine how a component of the brain, known as the amyloid protein, contributes to nerve cell degeneration. It is hoped that by identifying these mechanisms, new targets for drug development will be found.Read moreRead less
Application Of Intelligent Conducting Polymers For Treating Schizophrenia And Allied Disorders Focusing On Neuronal Outgrowth, Myelination And Synaptogenesis
Funder
National Health and Medical Research Council
Funding Amount
$698,314.00
Summary
This project involves cross-disciplinary collaboration between researchers at the forefront of materials engineering, nanotechnology, neural pathology, human stem cell biology and mental health disciplines. We will use a nanodevice to apply electrical stimuli and growth factors to improve brain function in schizophrenia and allied disorders.
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.