Molecular And Cellular Mechanisms Of Vertebrate Brain Development
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The essential steps in forming a normal functioning brain occur during life as an embryo. If these processes go haywire, there can be serious repercussions for life after birth. This project seeks to understand how the brain forms during embryonic stages so that better treatments and procedures can be developed to deal with developmental problems.
Deciphering The Mechanisms For Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$496,321.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
A Molecular Approach To Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells when these extra molecules are produced. The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
Membrane Fusion In Axonal Regeneration: Molecules And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Limited nerve regeneration is the main obstacle for recovery from spinal cord and brain injuries. Understanding the cellular and molecular mechanisms underlying axonal regeneration is an essential step toward the development of novel effective therapies to enhance this process. In this proposal, we use the powerful molecular and genetic tools available for the small nematode worm C. elegans to identify and study axonal regeneration and discover the key molecules involved.
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
Modulation Of Neurotrophin Receptor Signaling: Understanding The Determinants And Phenotypic Consequences.
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those where there is a primary loss or degeneration of neurons and-or their axons; and those where the Schwann cells are lost. These degenerative pathologies have prompted interest in the p ....Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those where there is a primary loss or degeneration of neurons and-or their axons; and those where the Schwann cells are lost. These degenerative pathologies have prompted interest in the potential of growth factors as a general therapy for peripheral neuropathy. The neurotrophins are a family of neuronal growth factors that influence many key aspects of neuronal development, as well as the maintenance of the mature peripheral nervous system. Work in cells in vitro and in animal models provides solid support for the hypothesis that the neurotrophins prevent neuronal death. However clinical trials testing the neurotrophins has led to variable results and side effects due to their many effects. To make these therapies useful, it is crucial to expand our knowledge about how they actually work and which of the many responses they induce actually produces their beneficial effect. This project aims to achieve this goal. I have identified a mechanism where neurotrophin signaling is selectively modulated in vitro. The aims of this project are to understand how this modulation of neurotrophin signaling is mediated, to identify the cellular substrates that are selectively activated and to determine what the biological consequences of this modulation are. Only through analyses such as these can we gain new insights into neurotrophin signaling and develop an understanding of how the activities of neurotrophins can be more precisely harnessed to generate new and more productive therapeutic approaches.Read moreRead less
Synaptic Transmission In The Mammalian Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$460,500.00
Summary
In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. Th ....In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. The overall aim of this proposal is to understand the basic mechanisms underlying synaptic transmission at excitatory and inhibitory synaptic connections in the mammalian brain. We will investigate specific synaptic connections in the central pathways of the auditory system, because our previous studies have demonstrated a number of key technical advantages in studying these synapses. We will use electrophysiological recording from synaptic terminals and neurons in isolated living slices of the brainstem of mice. We will use imaging techniques and electron-microscopy to examine the structural details of synaptic connections, as structure is thought to play a major role in determining the strength of synaptic transmission. We will also study the structural and functional properties of auditory synaptic connections in congenitally deaf animals. Our recent study comparing normal and congenitally deaf mice has already revealed significant differences. Our results will provide important insights in the regulation of synaptic strength in the central nervous system, and into the regulation of synaptic transmission at central synapses which have developed under conditions of abnormal sensory activation.Read moreRead less