Controlling The Development And Function Of Hindbrain Commissures In Vertebrate Animals: The Role Of Robo3 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$393,834.00
Summary
Commissural axons connect and coordinate activity between neurons of the left and right sides of the central nervous system. In the forebrain, formation of commissural axons is determined by guidance factors at the midline between the two hemispheres, and abnormalities in guidance can cause developmental malformations. The aims of this project are to elucidate function of the Robo/Slit family of molecules in regulating axon guidance of commissural neurons, particularly in the corpus callosum.
Neurexin And Neuroligin: A Code For Synaptic Development
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
As soon as we are born, we interpret our world through our senses, learn new information and lay down memory. These processes require molecules that connect neurons together. Mutations in genes encoding these molecules result in incorrect wiring of the brain and lead to mental disorders such as autism and schizophrenia. Using simple insect models, our project aims to unravel the fundamental mechanisms of how these molecules function in the brain and how their interaction controls behaviour.
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.
Normal And Abnormal Development Of Brain Wiring And Its Impact On Brain Function
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
My laboratory is striving to understand how the patterns of neuronal connections form in the developing brain and how these underpin the functions of the brain throughout life. We use high-field magnetic resonance imaging to measure brain wiring and we investigate the genetic and environmental mechanisms causing developmental brain disorders that result in intellectual disability, autism, epilepsy and some mental illnesses.
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
TorsinA Mediated Dystonia, Functional Analysis And Molecular Models
Funder
National Health and Medical Research Council
Funding Amount
$479,817.00
Summary
The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years se ....The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years several genes have been identified that can cause dystonia. The overall aim of this proposal is to characterise a gene that causes dystonia when disrupted. Understanding the function of this gene may significantly advance our understanding of this disorder. Using these results, we aim to model dystonia in cellular and animal systems; these may provide powerful insight into the molecular pathway(s) perturbed in dystonia and a means to develop novel therapeutic approaches to alleviate or prevent the disorder.Read moreRead less
A Novel Mechanism For Therapeutically Modulating Neurotransmitter-activated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$667,529.00
Summary
This project aims to elucidate the mechanisms by which macrocyclic lactones bind to brain ion channel receptors. This will reveal fundamental new insights into the operation of these receptors and will have important implications for the design of novel treatments for a variety of central nervous system disorders.
The Role Of The Gtf2i Gene Family In Behaviour And Williams Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$629,396.00
Summary
Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic ....Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic overfriendly, gregarious personality with little inhibition towards strangers. Such a characteristic cognitive and behavioral profile in a genetic disorder has provided convincing evidence that genes play a role in specifying cognitive abilities and behavior. This interesting syndrome gives us an insight into the perplexing debate of Nature vs Nurture. It also provides a unique and invaluable opportunity to dissect the role of certain genes in complex neurodevelopmental pathways that result in cognition and behavior. Recently, patients with smaller (atypical) deletions of genes in the WS region have been described. These patients do not display the full 'classical' range of WS characteristics. The identification of which genes are deleted in these patients suggests that two genes in particular, GTF2IRD1 and GTF2I, are involved in visuospatial abilities, sociability and specific anxieties and phobias. Our laboratory was the first to identify proteins encoded by GTF2IRD1, known as MusTRDs, that act for the most part to suppress gene expression. Furthermore, our laboratory has been studying a mouse model in which the Gtf2ird1 gene has been deleted, similar to the situation in WS, and have found that the mice are more 'social' and exploratory. In this project, we want to determine if other behavioural features of WS are contributed to by this gene and-or its related gene, Gtf2i, and to characterize the role that these genes play in neuronal cell function.Read moreRead less
Role Of Dynamin In Modes Of Synaptic Vesicle Endocytosis
Funder
National Health and Medical Research Council
Funding Amount
$905,985.00
Summary
Neurons communicate by neurotransmitter release from synaptic vesicles stored in nerve endings. There is a finite vesicle number, so they are recycled (endocytosis) by dynamin. Our aim is to reveal the molecular mechanisms underlying endocytosis to better understand diseases of the synapse like epilepsy. We propose that two forms of the dynamin gene mediate two forms of endocytosis, one of which is activated only under conditions of high neuronal firing, such as occurs during a seizure.