Molecular And Cellular Mechanisms Of Axon Growth And Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$467,545.00
Summary
There are millions of nerve cells in the vertebrate brain, each forming very precise and specific connections within neural circuits. During development of the embryo most of these cells are wired together. A Telstra technician will use the different colours of telephone cables to correctly connect them. Likewise, the growing processes of nerve cells in the brain use specific markers or labels as cues to establish the correct wiring. The aim of the present project is to characterize the specific ....There are millions of nerve cells in the vertebrate brain, each forming very precise and specific connections within neural circuits. During development of the embryo most of these cells are wired together. A Telstra technician will use the different colours of telephone cables to correctly connect them. Likewise, the growing processes of nerve cells in the brain use specific markers or labels as cues to establish the correct wiring. The aim of the present project is to characterize the specific role of some of these labels on nerve cells during development. This project will provide new fundamental knowledge about how brain cells are wired together during development of the embryo. This knowledge is essential for establishing strategies to enhance repair of brain cells following ischemic, excitotoxic or mechanical injury.Read moreRead less
Characterisation Of Neural Stem Cells In The Ageing Mammalian Brain
Funder
National Health and Medical Research Council
Funding Amount
$182,411.00
Summary
Due to their relatively recent discovery, little is known about how stem cells in the brain are affected by age. This work will initially focus on understanding how age affects the number of stem cells found in the brain, and how their normal function and regenerative capacity are compromised with increasing age. The second phase of this study will examine how we can slow or even reverse these age-related changes on stem cells by environmental manipulation.
How Does The LRP Receptor Megalin Promote Regenerative Neuronal Growth?
Funder
National Health and Medical Research Council
Funding Amount
$408,739.00
Summary
Promoting the regenerative growth of neurons to allow recovery from traumatic brain injury or Alzheimer's disease is a major goal of neuroscientists. This project continues the Chief Investigators' work in which they have discovered the regenerative potential of a protein and focuses on how this protein interacts with a key neuronal receptor, megalin, which appears to drive the regenerative process. This work will identify new targets for therapies for a range of nervous system disorders.
Roles Of Brain-derived Neurotrophic Factor In Plasticity Of Injured Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$461,443.00
Summary
The fundamental problem of how nerve cells respond to a nerve injury has long been studied by neuroscientists and clinicians. After a nerve injury outside the brain or spinal cord, ie, in the periphery, some sensory nerve cells die, some regenerate to reconnect to their targets, and some sprout to make abnormal connections. Recent evidence from our lab and others indicates that the nerve sprouting is linked to chronic pain experienced by nerve-injury patients. However, how these changes occur st ....The fundamental problem of how nerve cells respond to a nerve injury has long been studied by neuroscientists and clinicians. After a nerve injury outside the brain or spinal cord, ie, in the periphery, some sensory nerve cells die, some regenerate to reconnect to their targets, and some sprout to make abnormal connections. Recent evidence from our lab and others indicates that the nerve sprouting is linked to chronic pain experienced by nerve-injury patients. However, how these changes occur still remains largely unknown. Our recent studies showed that growth factors, particularly brain-derived neurotrophic factor (BDNF) which is made by the sensory nerve cells, may play important roles in mediating these changes. This proposed project, directly evolved from our recent exciting findings, aims to further examine roles and action mechanisms of BDNF and its relatives in regulating the responses of sensory nerve cells to a nerve injury. We propose that after an injury, BDNF promotes survival of some nerve cells, enhances sensory nerve regeneration in both periphery and spinal cord, and also mediates abnormal nerve sprouting and is involved in neuropathic pain. With strong expertise and powerful tools in hand, we have designed a series of experiments to investigate the roles and action mechanisms of BDNF and its related molecules in these processes. Results from this project will help us understand mechanisms underlying the responses of nerve cells to a nerve injury, and should provide much needed information which would help in designing new methods for enhancing nerve cell survival and nerve regeneration as well as for inhibiting nerve injury-induced chronic pain in nerve-injury patients.Read moreRead less
MECHANISMS OF TRANSMITTER SECRETION AT SYMPATHETIC NERVE VARICOSITIES
Funder
National Health and Medical Research Council
Funding Amount
$438,707.00
Summary
The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, ....The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, synaptobrevin, SNAP25 and synaptotagmin) together with a calcium channel are complexed with a docked synaptic vesicle containing a quantum of transmitter in a module of secretion appropriately called a secretosome. The leading questions here are to determine if only a single secretosome participates in transmitter release on the arrival of a nerve impulse, whether the number of these secretosomes in a varicosity determines its probability for secretion of a quantum, and fundamentally, how do the proteins within the secretosome cooperate to trigger exocytosis when there is sufficient calcium influx through the secretosome-associated calcium channel following the impulse. The other problem concerns the mechanism of removal of calcium from the varicosity once it has entered through the channels, This calcium can have considerable affects on the extent to which secretosomes participate in secretion with subsequent impulses. Furthermore, this influx of calcium can be modulated for subsequent impulses by transmitter released by the first impulse. The present research will solve these problems, providing a molecular description of secretion from single sympathetic varicosities.Read moreRead less
Suppressor Of Cytokine Signalling-2 (SOCS2) And Its Role In Neuronal Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are ....Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are examining factors which influence this process, which is called differentiation. Growth factors are important mediators of this process and suppressor of cytokine signalling (SOCS) proteins are important in determining how cells respond to growth factors. The overall aims of this project are to determine the role that SOCS genes and in particular, SOCS2 play in neural stem cell differentiation into neurons and glia, neuron process outgrowth and neuronal and glial injury responses in the nervous system. This will be examined in normal cells and cells which over-express or do not express SOCS2 genes. Understanding the biology of neural growth factor responsiveness may eventually allow us to devise therapeutic strategies for use following brain-spinal injury or disease, including generation of neurons from stem cells.Read moreRead less
Development And Refinement Of Neural Connections In The Adult Brain In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,061,596.00
Summary
Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a ....Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less
Molecular Mechanisms That Help Organise Effective Synaptic Transmission.
Funder
National Health and Medical Research Council
Funding Amount
$555,825.00
Summary
This study will test the idea that adhesion molecules alpha4- and beta2-laminin are needed for proper development and function of motor nerve - muscle connections. This study will provide insights into how such molecules control effective nerve-muscle communication, in both health and disease. We also believe that our results will provide the basic knowledge needed for identifying pharmacological targets that could improve such connections, and to promote reconnections between nerve and muscle.