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
EphA2 And EphA3 Maintain Tumour Initiating Cells And Are Therapeutic Targets In Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$612,860.00
Summary
High-grade glioma (HGG) is the most common adult brain cancer; current treatments have increased survival times by months only. Our studies have shown brain cancer specific expression of a family of cell surface proteins called Eph receptors. Furthermore we have shown targeting these receptors with Eph antibodies leads to a significant reduction in brain cancer tumour growth. We now propose to test targeting these receptors in combination to achieve greater responses with minimal side effects.
Therapeutic Potential Of Inhibiting Eph/ephrin Signalling To Repair The Vascular Endothelium In Septic Shock
Funder
National Health and Medical Research Council
Funding Amount
$664,734.00
Summary
Septic shock is a life-threatening condition usually caused by bacterial infection in the bloodstream. More than 5000 people, including 500 children, die from sepsis each year in Australia. Worldwide, it is the most significant cause of death in children. Sepsis is associated with leakage of fluid and proteins through the cells lining the blood vessels. This project will develop and test a novel treatment for sepsis which focuses on reducing this leakage by blocking the Eph/ephrin proteins.
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.
EphA3, A Novel Target For Leukaemia Stem Cell Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,992.00
Summary
Patients with acute myeloid leukaemia often respond to therapy, but many relapse due to “leukemic stem cells” (LSC), the few cells in the original leukaemia which survive therapy. We focus on a protein (EphA3) which sits on LSCs and helps them interact with their environment. Disrupting this interaction may make these cells vulnerable to therapy. We aim to determine the function of EphA3 on LSCs and optimise the therapeutic use of an antibody against EphA3 which is currently in clinical trial.