Targeting CD4-positive Cells For Anti-HIV Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$356,646.00
Summary
Treatment of HIV early following infection is thought to be important for maximising the quality of life of patients. Conventional therapy has had some success in early intervention but resistance invariably develops. This application proposes to develop a gene therapy approach to elimiate HIV infected cells by introducing a suicide gene into those cells that harbor the virus. The advantage of this approach is the limited toxicity that is associated with gene therapies as well as the ability to ....Treatment of HIV early following infection is thought to be important for maximising the quality of life of patients. Conventional therapy has had some success in early intervention but resistance invariably develops. This application proposes to develop a gene therapy approach to elimiate HIV infected cells by introducing a suicide gene into those cells that harbor the virus. The advantage of this approach is the limited toxicity that is associated with gene therapies as well as the ability to target specific cell-types. It is proposed to genetically modify a strain of adenovirus to introduce a gene that will kill cells that it infects that also contain HIV. This is a novel approach and potentially may be an important treatment in the future. Anti-HIV gene therapy may also be useful in addition to the more conventional treatments.Read moreRead less
Neural Control Of Behavioural State And Cognition - Role Of Nucleus Incertus And Relaxin-3
Funder
National Health and Medical Research Council
Funding Amount
$600,771.00
Summary
Dementia and mental illness are significant social and economic burdens worldwide and knowledge of underlying causes and more effective therapies are required. Our research is using preclinical models to characterize a little studied neural network in the control of arousal states, rhythmic brain activity, and learning and memory. Our findings could advance the development of improved treatments for cognitive deficits in degenerative, age-related and psychiatric disorders.
Investigation Of The Role Of Hypothalamic Y1 Receptors In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$329,625.00
Summary
The worldwide prevalence of obesity alarming, and is a major risk factor for diseases such as type 2 diabetes. Although the benefits of weight loss in overweight subjects are undisputed, there currently exists no effective long-term treatment for obesity. Therefore pharmacological interventions for obesity could dramatically reduce the burden of this disease. There is much interest in the development of treatments for obesity that prevent the action of proteins in the brain that are thought to l ....The worldwide prevalence of obesity alarming, and is a major risk factor for diseases such as type 2 diabetes. Although the benefits of weight loss in overweight subjects are undisputed, there currently exists no effective long-term treatment for obesity. Therefore pharmacological interventions for obesity could dramatically reduce the burden of this disease. There is much interest in the development of treatments for obesity that prevent the action of proteins in the brain that are thought to lead to increased food intake and gain of body fat, such as neuropeptide Y and its receptor Y1, both of which are found in the hypothalamus in regions known to regulate body fat. However, the true role of Y1 receptors in regulating body weight in the hypothalamus is currently unclear, since there are no known pharmacological tools that can specifically block or activate this receptor in order to demonstrate its function. To circumvent this problem we have developed genetically modified mice that enable us to specifically delete the Y1 receptor from the hypothalamus of adult mice, and therefore determine its role in regulating body weight. This project will demonstrate whether hypothalamic Y1 receptor deletion can reduce food intake and body fat in mice in the long-term, and whether it can cause other changes in metabolism that might also contribute to reducing body fat. We will also show whether the obesity that results from either a high-fat diet, from an excess of the stress hormone corticosterone, or from genetic mutation in mice, can be prevented or reversed by deletion of hypothalamic Y1 receptors. The results will be instrumental in deciding whether developing medicines that specifically block Y1 receptors in the hypothalamus will be of significant benefit for the long-term treatment of human obesity, which is caused by multiple genetic and environmental factors.Read moreRead less
Ascending Control Of Behavioural State And Cognition - Role Of Nucleus Incertus And Relaxin-3 Transmission
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Mental illness and dementia are significant social and economic burdens worldwide and knowledge of their underlying causes and more effective therapies are required. Our research aims to use pre-clinical models to characterize a little studied neuronal network implicated in control of brain theta rhythm activity, which could lead to improved treatment of neuropsychiatric diseases such as anxiety and depression, and degenerative cognitive decline.
Signalling Pathways Activated By Atrial Dilatation And Their Relationship To Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$449,878.00
Summary
Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4 ....Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and its immediate precursor phosphatidylinositol(4,5)bisphosphate (PIP2) in atrial fibrillation with a view to providing targets for therapy that are well tolerated. There is recent evidence that Ins(1,4,5)P3 and PIP2 can contribute to atrial fibrillation. Over the next 3 years we will study cellular signalling responses to acute and chronic dilatation of the atria and examine the relationship of these findings to clinical atrial fibrillation. We will identify the G protein and phospholipase C subtypes involved in responses to stretch and use tools developed in these studies in experiments with atrial fibrillation models.Read moreRead less