Tuberous Sclerosis And Epilepsy: Using Resected Tissue To Understand Pathogenesis And Inform Management
Funder
National Health and Medical Research Council
Funding Amount
$339,261.00
Summary
Epilepsy is the commonest neurological disorder in childhood and seizures cannot be fully controlled by medications in 30%, often leading to developmental consequences. A major cause of drug-resistant epilepsy is a malformation of the brain’s surface. Surgery is sometimes used to remove these lesions to treat the epilepsy. We will study this tissue to understand its architecture, genetic basis and how it causes seizures. Our results will guide treatment including the best surgical approach.
The Role Of Reelin-signalling On Cortical Neuron Migration
Funder
National Health and Medical Research Council
Funding Amount
$716,196.00
Summary
Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of d ....Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of development neurons are generated in one part of the brain and migrate great distances to a final destination. It is therefore necessary during development to have a well-orchestrated, controlled series of events that lead to the correct positioning and association of neurons. The precise functions of many gene products involved in this process are not known. One major advancement in the development of the cortex is the discovery of the protein Reelin which is found in the outermost region of the developing cortex. Mutations in Reelin, in humans, have been implicated in the causation of schizophrenia and mood disorders. These disease states are the result of altered migration of neurons in the cortex. The research proposed in this application is designed to understand the precise process of how two types of neurons migrate and assemble in the cortex. Technology today allows us to visualize, in culture, neurons as they migrate in real-time. This is referred to real time-lapse imaging and allows the researcher the ability to examine how external factors, affect migration of cortical neurons. We will determine how Reelin is involved in this process and our research will elucidate the fundamental process of cortical brain development.Read moreRead less
Advancing The Evidence-base For Childhood Brain Insult: Diagnosis, Assessment And Intervention
Funder
National Health and Medical Research Council
Funding Amount
$575,662.00
Summary
My research has 4 primary objectives, representing major gaps in current knowledge: 1. improve knowledge of recovery and determinants of post-concussive symptoms 2. establish the impact of child brain insult on socio-emotional function and identify contributing factors 3. develop an iPad based tool for socio-emotional function 4. evaluate and disseminate e-heath treatments for child brain insult
Combining Timelapse Imaging And Computational Modelling To Understand The Mechanisms Of Axon Guidance In The Developing Retinotectal System
Funder
National Health and Medical Research Council
Funding Amount
$438,793.00
Summary
Understanding how patterns of brain wiring develop is crucial for understanding many cognitive disorders. One of the commonest types of connection pattern in the brain is a topographic map, where nearby neurons in one structure connect to nearby neurons in another structure. Using the transgenic tools available in the zebrafish as a model system, we will combine novel experiments with computational modelling to understand the rules which govern the formation of topographic maps in the brain.
Targeting Of Callosal Axons To Duplicate Cortical Areas In The Contralateral Hemisphere
Funder
National Health and Medical Research Council
Funding Amount
$600,785.00
Summary
The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain ....The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain is wired in order to function correctly.Read moreRead less
Guidance Mechanisms Regulating The Development Of Axonal Projections From The Cingulate Cortex.
Funder
National Health and Medical Research Council
Funding Amount
$484,236.00
Summary
The corpus callosum is the largest fibre tract in the brain and connects neurons in the left and right cerebral hemispheres. A subpopulation of callosal axons arise from neurons in the cingulate cortex and are the first to cross the midline. Defects in activation or wiring of the cingulate cortex are strongly implicated in acute pain, schizophrenia and bipolar disorder. This proposal investigates how the commissural projections of the cingulate cortex become wired up during development.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Cellular And Molecular Regulation Of Interhemispheric Fusion
Funder
National Health and Medical Research Council
Funding Amount
$449,489.00
Summary
In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the ....In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the interhemispheric fissure to mediate fusion.Read moreRead less
Sez-6 Signalling Mechanisms And Function In The Developing Neocortex
Funder
National Health and Medical Research Council
Funding Amount
$501,815.00
Summary
Over the course of evolution, the mammalian brain cortex has become disproportionately large with respect to other brain regions. The dramatic increase in processing power resulting from the increased neuronal number and connectivity in the cortex has enabled us to acquire functions that make us human, such as the use of language. In spite of the enormous difference in size between the brains of humans and those of mice, studies on cortical development in mice are relevant to humans since the or ....Over the course of evolution, the mammalian brain cortex has become disproportionately large with respect to other brain regions. The dramatic increase in processing power resulting from the increased neuronal number and connectivity in the cortex has enabled us to acquire functions that make us human, such as the use of language. In spite of the enormous difference in size between the brains of humans and those of mice, studies on cortical development in mice are relevant to humans since the organization of the cortex (thickness, layer patterning and regional specialization) is very similar in these two organisms, and indeed, in all mammals. A complex series of developmental events is required to produce a normal brain cortex. Malformations in the cortex occurring in human neurological disorders, including epilepsy and mental retardation, result from mutations in genes regulating crucial developmental processes. Failure of developing nerve cells to make the correct connections can result in these, or other, debilitating neurological conditions. We have evidence that a brain protein called Seizure-related gene 6 (Sez-6) regulates normal connectivity and function of neurons in the mature cortex. We will determine the molecular pathways used for signalling of Sez-6 and also investigate in detail the formation of connections between cortical neurons early in development and how these connections become aberrant in the absence of Sez-6 function.Read moreRead less
Neurodevelopmental Mechanisms And Early Intervention In Psychiatric Illness
Funder
National Health and Medical Research Council
Funding Amount
$652,765.00
Summary
Schizophrenia and depression are devastating mental illnesses and a huge burden to society. Drug treatments can be beneficial, but many patients are either treatment-resistant or show severe side-effects. There is an urgent need for truly novel treatment strategies which should ideally prevent symptoms. The main aim of this project is to elucidate brain mechanisms involved in schizophrenia and depression development to inform clinical research about improved preventative treatment strategies.