Understanding the biological mechanisms of nerve degeneration is an essential step toward the development of novel therapies for human neurodegenerative conditions such as Parkinson's, Alzheimer's and Huntington's diseases, and for spinal cord injuries. The studies presented in this proposal, using the powerful molecular and genetic tools available for the small nematode worm C. elegans, will provide new insights into the cellular and molecular mechanisms responsible for nerve degeneration.
Segmentation Of The Peripheral Nervous System - The Role Of Axon Guidance Factors.
Funder
National Health and Medical Research Council
Funding Amount
$190,331.00
Summary
Injury to the nervous system results in great loss to the individual and society at large. To repair a damaged nerve pathway so that functional recovery may ensue is the pre-eminent goal of neuroscience research. An understanding of how factors that guide nerve processes coordinate the wiring of the nervous system during development of an embryo will provide an insight into what strategy is required to repair a damaged nerve pathway in the mature nervous system. In this research project we propo ....Injury to the nervous system results in great loss to the individual and society at large. To repair a damaged nerve pathway so that functional recovery may ensue is the pre-eminent goal of neuroscience research. An understanding of how factors that guide nerve processes coordinate the wiring of the nervous system during development of an embryo will provide an insight into what strategy is required to repair a damaged nerve pathway in the mature nervous system. In this research project we propose to investigate what factors guide the formation of the peripheral nervous system which controls the body. We will use a novel model system whereby a whole chick embryo is grown in a culture dish and the developing nerve pathways can be manipulated to discover what are the exact factors that guide nerve processes to wire up pathways to the limbs and other body parts. This research will provide an opportunity to study the basic principles of nerve pathfinding which may then be applied to more complicated circuits within the brain and to the repair of injured nerve pathways.Read moreRead less
Regeneration And Repair In The Rodent Visual System: An In Vivo Gene Therapy And Neural Transplantation Study
Funder
National Health and Medical Research Council
Funding Amount
$426,000.00
Summary
In the adult human central nervous system (CNS), traumatic injury, stroke, or loss of nerve cells due to degenerative disease all result in long-term and severe functional impairments. The personal, social and economic costs associated with these neurological problems are massive. In the proposed work, gene therapy and transplant techniques will be used to develop new cooperative strategies for neural repair. The aims are to protect and-or replace damaged nerve cells (neurons) and promote the lo ....In the adult human central nervous system (CNS), traumatic injury, stroke, or loss of nerve cells due to degenerative disease all result in long-term and severe functional impairments. The personal, social and economic costs associated with these neurological problems are massive. In the proposed work, gene therapy and transplant techniques will be used to develop new cooperative strategies for neural repair. The aims are to protect and-or replace damaged nerve cells (neurons) and promote the long-distance regrowth of their processes (axons). The ultimate goal is to improve the treatment of human CNS injury and disease, leading to better functional recovery. We will use the visual system as our experimental CNS model. Viruses are novel tools that can be used for the introduction of foreign genes into cells. We will use modifed, non-harmful viral vectors to genetically alter retinal neurons. We will incorporate extra copies of known neuroprotective and-or growth-promting genes into retinal cells and analyze whether these genetically engineered neurons possess a greater ability to survive and regenerate their axons after injury. We will combine this approach with the transplantation of peripheral nerve bridges which are known to boost the regrowth of CNS axons. We will also test the effects of viral transfer of genes into retinal neurons in transgenic mice that have already been given an 'extra dose' of a neuroprotective gene. We will determine if different genes cooperate together to produce a synergistic therapeutic effect after CNS injury. The above studies focus on regeneration in what are essentially acute injury models. We are also interested in the restoration of circuitry in chronic situations, where the damage occured some time previously and neurons have already been lost. We will therefore graft neural precursor cells into the rat eye in an attempt to replace endogenous retinal neurons that are dying or have been lost due to injury.Read moreRead less
Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
During development, the brain establishes intricate and precise connections. In several brain pathways, little is known about the processes regulating this connectivity. Furthermore, it is likely that the same processes will be required to repair the injured- diseased brain. This project builds on our preliminary data, that Wnt proteins are important regulators of developing dopamine pathways, and has implications for dopamine disorders including Parkinson’s disease and addiction.
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
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.
Knowledge, Identification And Exploitation Of Dopaminergic Axon Guidance Cues Will Improve Cell Replacement Therapy For ParkinsonÍs Disease.
Funder
National Health and Medical Research Council
Funding Amount
$481,797.00
Summary
Many obstacles exist for cell transplantation in ParkinsonÍs Disease; namely poor graft survival, restoration of appropriate circuitry and adequate nerve fiber growth from new cells. Using knowledge of how neural circuits are established during fetal development, we will attempt to recapitulate these events following transplantation. Further, we will identify new and novel cues in regulating the connectivity and growth of these nerve fibers.