Regulation Of Astrocytic Gliosis And Axonal Regeneration In EAE By EphA4
Funder
National Health and Medical Research Council
Funding Amount
$532,352.00
Summary
Multiple Sclerosis (MS) is a debilitating disease with currently no effective cure. Apart from losing the protective insulating sheath called myelin, nerve cells are damaged and a scar forms. If this could be prevented then MS may be better treated. Using a model of MS called EAE, the role of a molecule, EphA4, will be examined for its ability to induce nerve loss and scar formation and to determine whether blocking it will promote repair, leading to a therapy for MS.
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
Defining The Role Of EphA5 In Olfactory Axon Growth, Guidance And Fasciculation
Funder
National Health and Medical Research Council
Funding Amount
$256,320.00
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. In addition, we will also examine the behaviour of live cells as they are growing. In the past all attempts to understand how nerve cell connections are formed in the olfactory system have used dead tissue that has been permanently preserved. In this project we have the unique opportunity to visualise living nerve cells to enable us to determine how the cells react to the guidance signals. The advantage of this approach is that it allows us to identify important interactions as they occur, rather than attempting to decipher them after they have occurred. An analogy would be watching a football game live and observing how goals were scored and appreciating the performance of individual players versus trying to guess from the final score how the game was played and who the key performers were. The results of these experiments will provide important information on the regeneration of olfactory nerve cells, as well as on the initial growth and targeting of these nerve cells.Read moreRead less
The Role Of Eph-ephrin Interactions In Mediating Mesenchymal Stem Cell Commitment, Migration And Bone Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
In Australia, there is an increasing incidence of fractures that require surgical intervention and rehabilitation therapy. Fracture healing is a complex process that involves the coordination of different bone and immune cells. Our proposal will identify which cell-cell contact molecules mediate bone cell recruitment and development during normal skeletal growth and bone fracture repair. This study will help advance therapies for fracture repair and diseases of bone loss.
Mesenchymal Stem Cell Maintenance And Recruitment During Skeletal Repair Are Dependent On EphB-ephrinB Signalling
Funder
National Health and Medical Research Council
Funding Amount
$611,827.00
Summary
There is currently a steady increase in surgical intervention and rehabilitation therapy for bone related fractures due to trauma or osteoporosis as a consequence of an aging population. Bone regeneration involves the coordinated participation of skeletal precursor cells, blood vessels and immune cells recruited from the surrounding tissues. This proposal examines the mechanisms mediating the maintenance and recruitment of skeletal precursor cells to sites of bone damage.
Tapasin And Major Histocompatibility Complex Class I Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. ....An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. This research proposal aims to examine the role of tapasin in this regard. A thorough understanding of the basic principles of peptide presentation to T cells is crucial to the design of effective vaccines. Furthermore it will also broaden our understanding of immunological responses to cancer, autoimmune diseases and infections.Read moreRead less
Molecular And Cellular Changes Following A Cortical Injury: What Role Do They Play In Regeneration?
Funder
National Health and Medical Research Council
Funding Amount
$499,625.00
Summary
Damage to the visual areas of the brain is common after, for example stroke, neurotrauma or hypoxia. The injury often manifests in the form of a scar caused by a specific type of brain cell (astrocyte). This scar acts as a barrier to the cells which transmit information (neurones), preventing re-establishment of connectivity, thus functional recovery. We will see if we can reduce this scar and enhance re-connectivity after injury by blocking some of the molecules that brain cells express.