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
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Stroke outcomes directly relate to brain tissue rescue. We have contributed to changes in clinical practice through many clinical trials of new protocols and therapeutic strategies. Our program will focus on brain salvage in the pre-hospital setting and the acute hospital environment. We will use novel approaches to enhance brain recovery and design new implementation strategies to maximise the benefits of these therapeutic advances.
Restoration Of Cognitive Deficits Induced By Diabetes Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$261,251.00
Summary
Diabetes is a known risk factor for the development of dementia. However the details of this association have not been known. Recent evidence consistently shows that the integrity of blood vessels in the brain may be central to the onset of dementia, and consistently, damaged brain blood vessels are often reported in diabetic patients and animal models. This project is the first to target in restoring the integrity of those brain blood vessels in order to reverse diabetes-associated dementia.
Restoration Of Diabetes Associated Cognitive Deficits Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$430,998.00
Summary
Diabetes is known to increase the risk of dementia. Although the mechanisms are currently unknown, a recently emerging body of evidence suggest that damaged blood vessels of the brain may be central to onset and progress of cognitive dysfunction. Consistently, the dysfunction of brain blood vessels is often observed in the brain of diabetes subjects. Therefore, this project will investigate whether the amelioration of disrupted brain blood vessels restores the cognitive function in diabetes.
Missing Voices: Communication Difficulties After Stroke And Traumatic Brain Injury In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$655,310.00
Summary
Acquired communication disorder (ACD) is a common result of stroke and traumatic brain injury (TBI) and has a devastating impact on victims’ everyday lives. Stroke and TBI occur more than twice as frequently in Indigenous as in non-Indigenous populations, but current uptake of communication rehabilitation services is low and long term outcomes for the individuals are unknown. This Australian first study will examine the extent and impact of ACD in urban and rural Indigenous Australians.
Dementia Associated To Diabetes: Prevention Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$719,770.00
Summary
Diabetic insulin resistance is reported to induce cognitive decline and dementia. An accumulating body of evidence suggest that compromised integrity of neurovascular unit and following changes in cerebral lipid homeostasis may be centrally involved in the neurodegeneration and cognitive deficits. Therefore, the project aims to prevent the insulin resistance-associated cognitive impairment by modulating the integrity of cerebrovasculature and lipid homeostasis.
REACH: Randomised Trial Of EArly Rehabilitation In Congenital Hemiplegia
Funder
National Health and Medical Research Council
Funding Amount
$972,777.00
Summary
Infants with asymmetric brain lesions are at high risk of congenital hemiplegia. This study compares modified CIMT to an equal dose of bimanual training in 150 infants recruited at 3-6 months. Both therapies will be parent-delivered supported by experienced clinicians. Outcomes include use of the impaired hand in bimanual tasks, cognitive and motor development at 12 and 24 months c.a. with measures of neural structure and functional connectivity at 24 months. Early interventions that attenuate
Developing New Therapeutic Strategies For Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Each year, over 1,500 Australians will develop brain cancer. Unlike many cancers, it cannot be prevented by lifestyle changes. Adults with brain cancer usually die within 2 years. The overall aims of this funding are to extend patients' lives and build brain cancer research in Australia so that we have the best chance of curing this disease. The expected outcome is clinical trial of drug candidates for the most common and most deadly brain cancer, high-grade glioma.
Development Of Microscope-in-a-needle Devices For Improved Clinical Diagnostics
Funder
National Health and Medical Research Council
Funding Amount
$327,746.00
Summary
We have developed a new high-resolution optical imaging technology. The unique aspect of our research has been to redesign the imaging probe, miniaturising it to a few hundred microns in diameter, and encase it in a hypodermic needle – a ‘microscope-in-a-needle’. We are developing specific imaging probes to aid in the assessment of lung disease; the diagnosis of liver disease; and integrated into a brain biopsy needle to enable safer brain biopsies.