Role Of Chemokines And Interferons In Neural Progenitor Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$521,178.00
Summary
Regeneration of the central nervous system following disease or injury is extremely limited and frequently results in substantial impairment. A potential therapy to replace damaged or killed nervous system cells is the use of neural stem cells. Neural stem cells are present in the central nervous system and frequently attempt, but fail to repair nervous system damage. This project aims to examine factors that regulate neural stem cell function including factors that may regulate their ability to ....Regeneration of the central nervous system following disease or injury is extremely limited and frequently results in substantial impairment. A potential therapy to replace damaged or killed nervous system cells is the use of neural stem cells. Neural stem cells are present in the central nervous system and frequently attempt, but fail to repair nervous system damage. This project aims to examine factors that regulate neural stem cell function including factors that may regulate their ability to migrate or become appropriate neural cell types. Of particular interest are factors known as chemokines that regulate cell migration as well as have a variety of other effects. In addition, interferons, which are inflammatory molecules present in the damaged nervous system and that we have shown affect neural stem cell function, may interact with chemokines and will also be examined. In addition to examining the effects of these factors on neural stem cells, the signalling pathways they use in these cells will also be determined.Read moreRead less
The Combined Use Of Transplantation And Gene Therapy Techniques To Promote Regeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$521,026.00
Summary
Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce gen ....Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce genes into cells, a method that allows targeted supply of molecules to the injured brain. Gene and cell therapy may eventually be of clinical benefit to injured patients. In a range of different experiments we will combine two different gene therapy approaches, various pharmacological agents and novel transplantation strategies in attempts to enhance the survival of affected nerve cells and promote the regrowth of damaged nerve fibres across injury sites in the injured adult rat visual system. Long-term vector-mediated expression of growth factors in neurons and in grafts may 'trap' regenerating axons, potentially reducing their outgrowth into distal, denervated target areas. It is therefore important to determine if temporal regulation of growth-promoting genes has additional beneficial effects on the ability of regenerating neurons to recognise and selectively regrow axons into appropriate CNS targets. An additional series of studies will thus be undertaken. We will test a new generation of regulatory vectors in which it is possible to switch the virally encoded genes on or off and thus control the level and timing of gene expression over a therapeutic range. We will then determine if the use of these regulatory viral vectors results in more consistent and robust growth of nerve fibres with better reconnections, in the longer term leading to better recovery of function.Read moreRead less
Computational Analysis Of The Influence Of Growth Cone Shape Dynamics On Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$346,406.00
Summary
For the brain to function correctly its neurons must be connected correctly. This project will use a novel mathematical approach to understand how growing nerve fibres find where to go in the developing brain. In particular we will use both experiments and computational analysis to understand how the shape of the tip of a growing nerve fibre helps the fibre navigate. This may help us understand the biological cause of many different types of mental disorders.
The Role Of Meninges In Midbrain Dopamine Development
Funder
National Health and Medical Research Council
Funding Amount
$378,311.00
Summary
Dopamine neurons are important for the control of movement, emotion and cognitive function, and are affected in a number of disorders such as Parkinson’s disease. Instrumental in improving our knowledge of disease etiology and the development of new therapies will be a greater understanding of how these cells are initially born during development. This project examines the role of the brain’s meninges in dopamine development and repair and will identify proteins and signaling pathways involved.
Novel Strategies To Promote Myelin Repair In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$597,865.00
Summary
Demyelinating diseases of the central nervous system such as multiple sclerosis have a lifelong impact and devastating impact on quality of life. We have identified that a growth factor, brain derived neurotrophic factor (BDNF), plays an important role in promoting myelination during development. We will investigate the potential of translating these findings into effective clinical treatment, by characterising the efficacy of BDNF in promoting CNS remyelination after a demyelinating insult.
Differential Changes In Cortical Tumour Necrosis Factor Signalling In Mood Disorders And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$642,078.00
Summary
Changes in inflammation-related pathways contribute to the symptoms of psychiatric disorders and tumour necrosis factor ? (TNF) is a protein central to regulating theses pathways. We have now shown that changes in pathways regulated by TNF are present in the brains of people with schizophrenia and mood disorders. This means that the symptoms experienced by those with the different disorders may be linked to differential changes in TNF-regulated pathways in the brain.
Which Neurons Maintain Sympathetic Vasomotor Tone?
Funder
National Health and Medical Research Council
Funding Amount
$567,918.00
Summary
High blood pressure is a major risk factor for cardiovascular disease, a major burden of disease worldwide. High levels of nerve activity that cause the blood vessels to constrict elevating blood pressure are characteristic of hypertension. We do not know which brain cells set and maintain this nerve activity. We will identify these cells, determine how they function and what regulates them. Ultimately we could control these cells treating the cause of hypertension or when clinical need arises.
The Role Of BDNF In Central Nervous System Myelination
Funder
National Health and Medical Research Council
Funding Amount
$478,235.00
Summary
Multiple Sclerosis (MS) is the most common neurological cause of disability in young adult Australians. The cause of MS is unknown and therapies are limited to reducing inflammation, which does not address the major problem of the disease: loss of myelin. This project directly investigates how myelin is formed and will identify key mechanisms in this process, which may eventually be developed into treatments for diseases such as MS.
Understanding The Molecular Basis Of Central Nervous System Myelination
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Oligodendrocytes are the cell type in the central nervous system that produce myelin, the insulating layer around nerve cells. Loss of oligodendrocytes and myelin are key features of multiple sclerosis. This project aims to clarify the mechanisms that control the myelination of nerve cells during normal development, allowing the development of strategies to promote myelin repair in human diseases such as Multiple Sclerosis.
Investigating Underlying Mechanisms Linking Type 2 Diabetes With Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$701,950.00
Summary
With type-2 diabetes representing a major risk factor for neurodegenerative diseases such as Alzheimer's disease, it is important to understand the underlying mechanisms. This project will provide significant insight into how T2D impacts the brain with a focus on how deficiencies in brain inuslin signaling drives neurodegeneration. We will also evaluate novel inuslin like molecules at improving brain insulin siganling and preventing or slowing down the neurodegenerative process.