The Role Of Innate Immune Memory In The Transition From Acute To Chronic Pain
Funder
National Health and Medical Research Council
Funding Amount
$331,440.00
Summary
Chronic pain costs Australians more than $34 billion annually and is the 3rd highest Australian disease burden. It has long been thought to be a disease of the wiring of the brain. This project aims to challenge this long held belief by examining the impact of the immune system in creating chronic pain. Such work promises to provide new and better ways to prevent chronic pain, which will improve & maintain good health for all Australians.
Therapeutic Targeting Of Neuroinflammation To Slow The Progression Of Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
My research has identified key components of our immune system, that can worsen disease in conditions such as Parkinson’s disease and motor neuron disease. I hope that exploring these components in animal models, and patients suffering from these diseases, my group can identify new therapeutic drug candidates that can be progressed in clinical trials. Ultimately, this may lead to new treatments to reduce disease burden in patients suffering from these neurodegenerative conditions.
The Role Of Neuronal Hyperactivity And Neurotrophic Factor Signalling In Synaptogenesis, Dendrogenesis And Neuron Death In Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$700,331.00
Summary
Using mice with mutant genes causing amyotrophic lateral sclerosis, we will test whether motor neuron hyper-excitability during early development causes excessive synapse and dendrite formation, ultimately leading to neuronal death. We will also test whether activity-dependent secretion of neurotrophic factors and activation of their receptors plays a role in this disease. This will show whether neuronal hyper-activity and neurotrophic factor signaling plays a causal role in this disease.
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.
LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor n ....LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor neuron development interact with each other and with DNA. With this information we are developing reagents that can be used to further probe central nervous system function and may ultimately be used to regenerate damaged nerves.Read moreRead less
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
Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of ....Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of novel therapies that promote neuronal regeneration relevant for disorders such as spinal cord injury and Alzheimer's disease, which constitute a large socio-economic burden in Australia. Currently, 400 people contract spinal cord injury every year, corresponding to an annual cost of $1 billion, and more than 500 000 aging people suffer from Alzheimer's disease.Read moreRead less
Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe ....Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe the fundamental process of cell differentiation in the central nervous system.Read moreRead less
Assessing The Role Of The N-terminus Of The Prion Protein, Emphasising Constitutive Cleavage, In Normal Function And Pathogenesis, As Well As Defining The Relationship Between Intensity Of Surveillance And Sporadic CJD Incidence.
Funder
National Health and Medical Research Council
Funding Amount
$387,469.00
Summary
As a neurologist undertaking research into prion diseases over an extended period, I have been able to lead and participate in many projects that have made significant contributions, such as validation of new diagnostic tests for Creutzfeldt-Jakob disease (CJD), assessment of potential therapeutics, provide insights into the normal function of the prion protein and the underlying pathways causing cellular damage and determine the real significance of apparent clusters of sporadic CJD.
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less