Understanding The Role Of The Olfactory Ensheathing Cell In The Olfactory Sensory System
Funder
National Health and Medical Research Council
Funding Amount
$494,000.00
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 how one specialized type of cell, the olfactory ensheathing cell, helps the nerve cells to grow and regenerate. Information we obtain about how this system develops and regenerates may be useful in treating brai ....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 how one specialized type of cell, the olfactory ensheathing cell, helps the nerve cells to grow and regenerate. 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 how olfactory nerve cells interact with the ensheathing cells. We will use transgenic mice in which the different cells are marked by separate colours which will allow us to easily identify the cells and see where they grow. 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 interact with the ensheathing cells. 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. These experiments will provide important information about how the olfactory ensheathing and nerve cells grow and regenerate.Read moreRead less
Olfactory Ensheathing Cells: A Major Contributor To Axon Guidance?
Funder
National Health and Medical Research Council
Funding Amount
$575,749.00
Summary
The olfactory (smell) system is a unique part of the nervous system because nerve cells are generated throughout life. Understanding how the olfactory system grows and regenerates may lead to therapeutic approaches to repair other regions of the nervous system. This project will use high resolution digital time-lapse imaging of living nerve cells and the specialised cells called olfactory ensheathing cells to determine how the behaviour of these cells can be manipulated to improve regeneration.
Cellular And Molecular Mechanisms Of Neuronal Repair By Olfactory Ensheathing Cells
Funder
National Health and Medical Research Council
Funding Amount
$218,250.00
Summary
Traumatic injury to the human brain and spinal cord often results in permanent disability. A major reason is that nerve fibres which act as cables connecting different parts of the nervous system are injured and fail to regrow. Failure of adequate repair is due to the fact that the central nervous system is a hostile environment, lacking in growth promoting stimuli and instead possessing growth inhibitory properties. One of the experimental methods used to alter this environment is the transplan ....Traumatic injury to the human brain and spinal cord often results in permanent disability. A major reason is that nerve fibres which act as cables connecting different parts of the nervous system are injured and fail to regrow. Failure of adequate repair is due to the fact that the central nervous system is a hostile environment, lacking in growth promoting stimuli and instead possessing growth inhibitory properties. One of the experimental methods used to alter this environment is the transplantation of olfactory ensheathing cells into the injury site. Ensheathing cells normally support the nerve fibres involved in the sense of smell. Tissue culture studies show that these cells produce on their surface specific types of molecules as well as soluble growth factors that could interact with nerve fibres to promote growth. Although experiments in which ensheathing cells have been injected into rat spinal cords, have resulted in varying degrees of recovery, the question of how they are able to do this remains unknown. The study proposed here will use tissue culture and in vivo models to investigate how ensheathing cells interact with their surrounding cells. In particular we will examine how soluble factors and direct membrane contact contribute to the regeneration of nerve fibres. We will also examine the effects that ensheathing cells have on non-neuronal cells such as astrocytes and oligodendrocytes and vice-versa. A significant outcome of this project is new insight into the complex cellular interaction that occurs to bring about repair in the central nervous system. The findings will pave the way for the future development of olfactory ensheathing cells as an effective therapeutic agent of nerve repair. This could also include genetic manipulation of ensheathing cells such that their properties are optimised specifically to promote regrowth of nerve fibres.Read moreRead less
Adult Stem Cell Transplantation Therapy In Parkinsonian Rat
Funder
National Health and Medical Research Council
Funding Amount
$526,517.00
Summary
Parkinson's disease is a progressive neurodegenerative disorder characterised by slowness of movement, muscle rigidity and tremor. It affects about 1% of the population at age 50 and 10% over age 80. Symptoms are caused by low levels of dopamine, a chemical in the brain that helps control movement. The symptoms increase in severity with time, leading to increasing difficulty in walking, speaking, writing, swallowing and sleeping and increasing the incidence of broken bones from falls. Parkinson' ....Parkinson's disease is a progressive neurodegenerative disorder characterised by slowness of movement, muscle rigidity and tremor. It affects about 1% of the population at age 50 and 10% over age 80. Symptoms are caused by low levels of dopamine, a chemical in the brain that helps control movement. The symptoms increase in severity with time, leading to increasing difficulty in walking, speaking, writing, swallowing and sleeping and increasing the incidence of broken bones from falls. Parkinson's disease is incurable but the symptoms can be controlled with medications that replace the lost dopamine. Medications become less effective as the disease progresses and there is need for new therapies. Worldwide the hunt is on to discover new cell transplantation therapies to replace the dopamine in the brain and to prevent degeneration of the still surviving dopamine cells. Although embryonic stem cells might be useful for such therapies, they raise the risk of tumour formation from the transplanted cells. This aim of this proposal is to test, in parkinsonian rat, a therapy in which adult stem cells from the patient are transplanted into their own brain to provide a new source of dopamine. We have discovered a new and unique source of adult stem cells, the sense organ of smell in the nose. Small samples can be taken through the nose and we can grow these adult stem cells from people of all ages, including people with Parkinson's disease. As adult stem cells they avoid the ethical issues associated with embryonic stem cell transplantation and as cells from the same patient, they are not rejected by the immune system. This is being tested in principle by a world-first clinical trial in which we are taking another cell type from the nose, growing it in the lab, and transplanting into the injured spinal cord in a search for a cure for paraplegia. This project takes the first steps to developing a new treatment for Parkinson's disease using a patient's own adult stem cells.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
Herpesviruses infect us all and cause cancer, blindness, and congenital disability. Developing vaccines requires information from both patients and experimental animals. CD4 T cells seem to suppress directly virus replication, and cells in the nose provide an important way for herpesviruses to get in. We will test whether CD4 T cells can clear nasal infection; what targets they recognize; and how they act. Thus we can establish whether CD4 T cell-directed vaccines might protect against disease.