A Novel Treatment For Ischemic Stroke: Preclinical Assessment In The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$762,246.00
Summary
A major source of repair inhibition after brain injury is debris from dying cells, which contains proteins that hinder repair. This project will examine the expression of these proteins in a clinically-relevant model of ischemic stroke and determine if blocking the effect of these proteins neutralises their repair-inhibiting properties. If successful, there is likelihood that this drug, and method of delivery, could be translated into the human for treatment following an ischemic stroke.
Next Generation Cybernetics: Long Term Carbon Fibre Dual Stimulation / Recording Electrode Arrays For Closed Loop Neural Implants
Funder
National Health and Medical Research Council
Funding Amount
$679,670.00
Summary
Electrodes implanted in the brain have enormous potential for treating a range of conditions from epilepsy to control of prosthetics for patients with limb loss. Currently, the electrodes used in such system fail rapidly because they are rejected by the body. We aim to use diamond with ultra-fine carbon fibre electrodes to make arrays that are invisible to the human immune system. Such arrays will function for the lifetime of the patient without needing replacement.
Knowledge, Identification And Exploitation Of Dopaminergic Axon Guidance Cues Will Improve Cell Replacement Therapy For ParkinsonÍs Disease.
Funder
National Health and Medical Research Council
Funding Amount
$481,797.00
Summary
Many obstacles exist for cell transplantation in ParkinsonÍs Disease; namely poor graft survival, restoration of appropriate circuitry and adequate nerve fiber growth from new cells. Using knowledge of how neural circuits are established during fetal development, we will attempt to recapitulate these events following transplantation. Further, we will identify new and novel cues in regulating the connectivity and growth of these nerve fibers.
Selective Isolation And In Vivo Properties Of Dopamine Neurons Generated From Embryonic Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$505,389.00
Summary
This research aims to develop a procedure that allows for the safe and effective use of stem cells as a therapy for Parkinson’s disease. It is based on the concept that new dopamine neurons, generated from stem cells, can be implanted into the brain of the patients in order to replace those lost to the disease, thereby improving motor function.
Brain Repair Following Stroke: The Role Of Npas4, A Neural-specific Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$611,053.00
Summary
Stroke is the #1 cause of adult disability in Australia and #2 cause of death. About 60,000 Australians suffer a stroke each year while about 250,000 live with the disabilities of stroke, costing over $2B/year. The Queen Elizabeth Hospital and University of Adelaide will study why the Npas4 gene switches on after stroke and the role it plays in brain repair. Future health benefits may be tests to help improve stroke outcome in patients and therapy to decrease loss of brain cells after stroke.
The Molecular Basis For Target Selection In The Central Nervous System By Sensory Axons
Funder
National Health and Medical Research Council
Funding Amount
$251,325.00
Summary
The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct conne ....The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct connections following injury to the brain or spinal cord. We propose to use a simple model system, the embryo of the fruitfly Drosophila, to find molecules that are involved in this process of neuron target recognition - ' axon targeting' molecules - and to study how they work. Drosophila can be genetically manipulated in ways not possible in higher animals. Furthermore the simplicity of its nervous system means that we can determine the connections of individual nerve cells with a high degree of precision. In the first part of our project, we will examine Drosophila embryos that carry mutations in genes suspected to code for targeting molecules. We will stain individual sensory nerve cells in these embryos with dyes to reveal the anatomy of their axons in the brain. If sensory axons terminate abnormally in the brain of a given mutant, the affected gene is likely to code for an axon targeting molecule. In the second part of the study, we will investigate the functions of candidate axon targeting molecules using two approaches. Firstly, we will seek to determine whether the molecule acts in the sensory axons or in their target cells. Secondly, we will use time-lapse microscopy to study how the homing behaviour of the sensory axons is affected in mutant embryos. The results of these studies will lead us closer to an answer to the question: How do axons recognise their specific target cells in the brain?Read moreRead less
The Role Of Cell Adhesion Molecules In Regulation Of Axon Advance
Funder
National Health and Medical Research Council
Funding Amount
$426,006.00
Summary
All cells contain on their surface a class of molecules, cell adhesion molecules, that enable them to adhere to other cells in tissues. Cell adhesion molecules have long been known to be involved in the guidance of axons to their targets during development. However the molecular mechanisms by which these molecules act are largely unknown. We propose to use the powerful genetic tools available in the fruitfly to dissect the mechanisms by which two cell adhesion molecules promote axon growth.
Using Stem Cells And Bioengineered Scaffolds To Promote Regeneration Following Necrotic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$710,857.00
Summary
A number of injuries, including stroke, result in tissue loss. Consequently promoting repair will require restoration of tissue structure, replacement cells and a supportive environment to promote integration of these new cells. This study will engineer and develop novel scaffolds that can replace tissue whilst additionally providing physical and chemical support for newly implanted stem cells. This work will be conducted in an animal model of stroke.
Standardising Protocols For The Differentiation And Integration Of Human Pluripotent Stem Cell-derived Neural Transplants In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$987,664.00
Summary
Clinical trials have shown that transplanting dopamine neurons (specific nerve cells) into the brain of Parkinson’s disease patients can improve symptoms. Trials use fetal tissue for implantation, which is unsustainable and highly variable. This proposal will examine stem cells as an alternative. We will establish a reliable protocol to instruct human stem cells to become dopamine neurons, develop methods to select these cells and, examine the integration of these transplanted cells in the brain
Reprogramming Macrophage Function In The Elderly To Rescue Impaired Inflammatory Responses To Muscle Injury
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Muscle injury in the elderly often takes longer to heal than in younger people, however the cells responsible for this delayed healing are not well understood. Key inflammatory cells required for muscle repair in young hosts are macrophages. However, during aging we have shown that macrophage function is altered, but the mechanism is unknown. This project aims to determine the mechanisms behind age-related changes to macrophages and whether they can be targeted to improve elderly muscle repair.