My research focuses on understanding pathobiological mechanisms in acute and chronic neurodegenerative conditions such as stroke and Parkinson’s disease which have large burdens on the community through health care costs and on families because of the lack of effective treatments. An improved understanding of how brain cells die and of how the most abundant brain cell, the astrocyte, can be engineered to be a resource for regenerative medicine offer promise for improved clinical management.
The amygdala is a part of the brain that processes and lays down emotional memories. Dysfunction in the amygdala is responsible for anxiety related disorders such post-traumatic stress disorder. I will study the neural circuits in the amygdala using innovative recordings and stimulation techniques. These studies will provide insight into the circuits that underpin anxiety related neurological disorders and provide targets for development of novel anxiolytic agents.
Characterisation Of The Molecular Mechanisms Of Abeta-induced Proteolysis Of The Neural Cell Adhesion Molecule 2 (NCAM2)
Funder
National Health and Medical Research Council
Funding Amount
$374,666.00
Summary
Neurons in the brain are connected by synaptic contacts. Amyloid beta peptide accumulating in the brain in Alzheimer’s disease destroys synaptic contacts by degrading synaptic cell adhesion molecules which maintain the structure of the contacts. The aim of the project is to characterise the molecular mechanisms of amyloid beta-dependent degradation of synaptic cell adhesion molecules. The project will identify strategies that can be used to inhibit synapse loss in Alzheimer’s disease.
Microglia As Primary Drivers Of Stress-induced Changes In Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$475,781.00
Summary
Persistent exposure to stressful events can produce serious and lasting disturbances in cognitive function. Our research group has recently identified that microglia may play a very significant role in these disturbances. The studies to be undertaken in this proposal will provide fundamental knowledge on how microglia contribute to neuronal plasticity, and how microglia via their effects on neurons regulate complex cognitive behaviour.
The Role Of LIM Domain Kinase 1 In The Pathogenesis Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$565,531.00
Summary
Alzheimer’s disease is characterized by progressive loss of cognition. Few Australians have remained untouched by the effects of Alzheimer’s disease in their families or social circles. Unfortunately, there is no cure and current therapies are limited to modest symptomatic relief. This project will explore the role of a protein that regulates the structural integrity of brain cells in disease, and test if targeting this protein could prevent disease progression.
Preclinical Development Of Complement C5aR Antagonists For The Treatment Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$593,326.00
Summary
There is no cure for Motor Neuron Disease (MND) resulting in 2 Australian’s dying each day. Modification of the inflammation is one potential means of slowing MND. Our research team has identified a new series of potent anti-inflammatory compounds that may have potential to treat this disease. Our project will test these compounds in animal models of MND, and validate their usefulness in human MND samples. Ultimately, this work may contribute to the discovery of a new treatment for MND.
Trials of numerous agents to slow the progression of Parkinsons disease have provided ambiguous or negative results despite having good preliminary evidence for their efficacy. The most likely reason is that many nerve cells are already destroyed by the time of diagnosis. Thus effective therapies may be most (and possible only) effective when administered in the presymptomatic stages of disease. This proposal is directed at developing method to detect early presymptomatic Parkinsons disease.
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.