THE NEUROBIOLOGICAL BASIS OF INDIVIDUAL DIFFERENCES IN SUSCEPTIBILITY TO THE CONSEQUENCES OF STRESS
Funder
National Health and Medical Research Council
Funding Amount
$583,875.00
Summary
Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those t ....Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those that tend towards active coping strategies, such as attempting to take control of the situation. Previous studies have provided findings that suggest that passive coping is more common amongst sufferers of depression, post-traumatic stress disorder, and chronic pain syndrome than is active coping. But is this cause, or effect? And what are the intervening brain mechanisms? We attempt to address such questions in the present project using an animal model in which social conflict has been shown to trigger depression-like symptoms. In particular we wish to: (i) determine whether the patterns of brain activity triggered by social conflict are different for active vs. passive copers; (ii) determine whether the depression-like consequences of social conflict are more severe in passive than in active copers; (iii) determine whether differences in coping style and vulnerability to social conflict stress are due to the actions of a particular neurotransmitter, dopamine, in the prefrontal cortex of the brain; (iv) determine whether the actions of antidepressants might be attributable changes in prefrontal cortex dopamine function which in turn promote active coping in preference to passive coping. These studies will provide exciting new information about the neurobiological basis of individual differences in vulnerability to the harmful effects of stress, and thus will offer the hope of developing new ways of preventing devastating illnesses such as depression.Read moreRead less
Investigation Of Neuregulin Precessing By Beta-site APP Cleaving Enzyme And Gamma Secretase In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$46,715.00
Summary
Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more s ....Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more selective therapies with less side-effects.Read moreRead less
The Role Of A Presenilin 2 Truncation (PS2V) In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,741.00
Summary
The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for t ....The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for the disease.Read moreRead less
Delineating The Mechanism Of Amyloid Beta Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$565,242.00
Summary
Alzheimer’s disease and beta amyloid toxicity: Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive memory loss, confusion, and cognitive deficits. In 2011, an estimated 269,000 Australians are currently living with dementia and without a significant medical breakthrough soon, it is anticipated that this will rise to about 981,000 by 2050
Exploring Scanning Ultrasound (SUS), A Novel Method To Treat And Prevent Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$765,708.00
Summary
We developed a novel scanning ultrasound (SUS) protocol that clears toxic protein aggregates and restores memory function in mouse models of Alzheimer's disease (AD), without the need for therapeutic agents. Here we aim to determine whether SUS has preventative potential, whether there are synergistic effects, and whether a therapeutic antibody combined with SUS leads to an enhanced therapeutic outcome. Together this will guide the development of an ultrasound therapy in AD patients.
Site-specific Tau Phosphorylation To Treat And Understand Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$943,902.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia. Unfortunately, current therapies are ineffective. Our laboratory has made an important contribution to understanding the events that lead to brain cell malfunction in AD. I recently found a novel concept that changes the view of AD completely. In the next 3 years, I aim to develop therapeutic tools based on this novel concept and find out more about how it can protect brains from AD.
TorsinA Mediated Dystonia, Functional Analysis And Molecular Models
Funder
National Health and Medical Research Council
Funding Amount
$479,817.00
Summary
The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years se ....The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years several genes have been identified that can cause dystonia. The overall aim of this proposal is to characterise a gene that causes dystonia when disrupted. Understanding the function of this gene may significantly advance our understanding of this disorder. Using these results, we aim to model dystonia in cellular and animal systems; these may provide powerful insight into the molecular pathway(s) perturbed in dystonia and a means to develop novel therapeutic approaches to alleviate or prevent the disorder.Read moreRead less
I am a neuroscientist working on determining the different pathogenic mechanisms occurring in neurodegenerative movement disorders and dementias, and translating these findings for clinical neurologists and neuropathologists.