How Are Axons Guided To Their Targets In The Developing Nervous System?
Funder
National Health and Medical Research Council
Funding Amount
$329,644.00
Summary
Many neurodevelopmental disorders are probably the result of wiring defects. In this project we will use new technologies to study how growing nerve fibres are steered to their targets during development, and use this data to create new mathematical models which can predict which way nerve fibres should grow in different situations. This will advance our understanding of the mechanisms underlying both normal and abnormal brain development.
Molecular And Activity Dependent Mechanisms Regulating The Targeting Of Corpus Callosum Axons In The Contralateral Hemisphere.
Funder
National Health and Medical Research Council
Funding Amount
$413,266.00
Summary
The brain is made up of circuits of neurons that process specific information. For example, the somatosensory cortex receives and sends connections to other somatosensory areas, including the contralateral cortex, but how these systems are wired up is not known. We will investigate whether information about the size and position of the cortical areas and activity-matching of the somatosensory information received by each hemisphere are used to guide callosal axons to their targets.
Genes Important For Early Brain Development Are Also Important For Adult Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
I committed to understanding of how the brain develops, grows and regenerates. My laboratory is active in finding a cure for brain injury following brain trauma or brain ischemia. I have discovered that the genes that drive neuron migration and wiring in the fetus also function in the adult brain to improve neuron survival and regeneration. Probing the function of these genes will deliver twin benefits in preventing brain disorder in the newborn and treating brain disease in the adult.
Role Of Chemokines And Interferons In Neural Progenitor Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$521,178.00
Summary
Regeneration of the central nervous system following disease or injury is extremely limited and frequently results in substantial impairment. A potential therapy to replace damaged or killed nervous system cells is the use of neural stem cells. Neural stem cells are present in the central nervous system and frequently attempt, but fail to repair nervous system damage. This project aims to examine factors that regulate neural stem cell function including factors that may regulate their ability to ....Regeneration of the central nervous system following disease or injury is extremely limited and frequently results in substantial impairment. A potential therapy to replace damaged or killed nervous system cells is the use of neural stem cells. Neural stem cells are present in the central nervous system and frequently attempt, but fail to repair nervous system damage. This project aims to examine factors that regulate neural stem cell function including factors that may regulate their ability to migrate or become appropriate neural cell types. Of particular interest are factors known as chemokines that regulate cell migration as well as have a variety of other effects. In addition, interferons, which are inflammatory molecules present in the damaged nervous system and that we have shown affect neural stem cell function, may interact with chemokines and will also be examined. In addition to examining the effects of these factors on neural stem cells, the signalling pathways they use in these cells will also be determined.Read moreRead less
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.
Exercise Reverses Cognitive Decline In Aged Animals By Growth Hormone Stimulation Of Neurogenesis In The Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$696,409.00
Summary
The production of new neurons in the hippocampus plays a critical role in learning and memory. With increasing age, this production slows and is associated with cognitive decline. However the stem cells that make new neurons are still present, and we have discovered that exercise activates these cells, leading to renewed neuron production and reversal of cognitive decline. We will explore how this process is regulated in order to develop strategies to reduce cognitive decline in humans.
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.
The Role Of Netrin-DCC In The Development Of The Corpus Callosum
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with ove ....During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with over 50 different human congenital syndromes. Thus understanding how the genes and molecules involved in the formation of the corpus callosum function in normal development can provide the basis for our understanding of what goes wrong in ACC. In this proposal we will investigate the role of the axon guidance molecule Netrin1, and its receptor DCC, in development of the corpus callosum in both a mouse model and in humans with malformations of the corpus callosum. Although Netrin1-DCC signalling has traditionally been associated with mechanisms of axon guidance, we hypothesize that these molecules may play a different role, specifically in cellular adhesion and ultimately in the fusion of the two cerebral hemispheres, in a manner that allows the corpus callosum to form. A second role for Netrin1-DCC signalling may be in the guidance of these axons once the midline has fused correctly and we investigate this in Aim 2 of the proposal. Finally, we are collaborating with a paediatric neurologist at UCSF, who has identified several mutations in the DCC gene in patients with ACC. In Aim 3 we test whether these mutations disrupt the function of DCC in callosal axon pathfinding. Understanding how these genes function during development of the brain and how their function may be altered in ACC is crucial to providing a proper diagnosis and prognosis for these patients. Ultimately, understanding more about how these genes function could also lead to prevention of these disorders.Read moreRead less
Roles Of Peripherally Derived BDNF In Regeneration Of Spinal Cord And The Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
Injury to the brain and spinal cord often leads to permanent disability due to lack of regeneration. The mechanism why central nerve does not regenerate is not known. Neurotrophic factors are powerful molecules which can overcome effects of inhibitory factors on regeneration. This project aims to investigate how neurotrophic factors override the effects of inhibitory factors and how to improve the regeneration by increasing the production of neurotrophic factors within nerves. Successful complet ....Injury to the brain and spinal cord often leads to permanent disability due to lack of regeneration. The mechanism why central nerve does not regenerate is not known. Neurotrophic factors are powerful molecules which can overcome effects of inhibitory factors on regeneration. This project aims to investigate how neurotrophic factors override the effects of inhibitory factors and how to improve the regeneration by increasing the production of neurotrophic factors within nerves. Successful completion of this project will help understanding the mechanism of how neurotrophic factors work on regeneration and developing the effective way to improve regeneration of the injured spinal cord.Read moreRead less