Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$564,721.00
Summary
A major obstacle in repairing the injured or diseased brain is inducing axons (nerve cell processes) to make the appropriate connections. This is especially true following cell replacement therapy (CRT) in Parkinson's disease (PD). We will examine the processes inducing axons in the dopamine pathways to grow. We hypothesize that Wnt signaling plays and important role and that therapeutic introduction of Wnt is required to repair the dopamine pathways following CRT in PD.
The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to tes ....The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to test and identify people at risk for type 1 diabetes. They showed that the underlying disease could start years before symptoms occurred and discovered genes that determine the rate at which the underlying disease progresses. They have also found evidence that the disease may be triggered by gut viruses called rotaviruses in genetically-susceptible individuals. They showed that type 1 diabetes could be prevented in a mouse model by getting the immune system to make a protective response to insulin, and then went on to apply this in at-risk humans in a controlled trial of intranasal insulin, the first of its kind. They have used genetic techniques not only to pinpoint the mechanisms responsible for killing the beta cells but also to modify the beta cells to make them resistant to attack by these mechanisms. The multidisciplinary approach of the team will be directed to further understanding the genetic and environmental factors underlying type 1 diabetes and the immune mechanisms, particularly involving special white blood cells called T cells, that kill beta cells. A molecular target of the immune attack, the parent of insulin called proinsulin, will be used, paradoxically, as a tool to regulate the immune system and avert the attack. This will be achieved by giving proinsulin via the mucosa of the naso-respiratory tract or via the bone marrow-derived stem cells, initiallyin the mouse model as a test of feasibility for human application. In parallel with these approaches to prevention, specially constructed viruses will be used to transfer several new genes into beta cells to improve their resistance to immune attack, so that they can be transplanted into people with established diabetes without the need for potentially toxic drugs that suppress the immune system overall. The integrated research of the team is helping to provide a sound, rational base for the eventual prevention and cure of type 1 diabetes.Read moreRead less
Novel Therpeutic Approaches For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,734.00
Summary
There are currently no effective treatments for Alzheimer's disease. In this application we will develop a novel class of compound to assess their potential as AD therapeutics. These compounds will be tested in vitro and in vivo models of Alzheimer's disease. The successful conclusion of the work described here would provide new leads suitable for further development as therapeutics for Alzheimer's disease.
Regulation Of Lipid Metabolism By AMP Activated Protein Kinase
Funder
National Health and Medical Research Council
Funding Amount
$478,776.00
Summary
Western communities are experiencing an epidemic of overweight and obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating an enzyme, called AMP-activated protein kinase, that plays a pivotal role in controlling how our bodies control energy metabolism in response to exercise. Improved understanding about how this enzyme regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines ....Western communities are experiencing an epidemic of overweight and obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating an enzyme, called AMP-activated protein kinase, that plays a pivotal role in controlling how our bodies control energy metabolism in response to exercise. Improved understanding about how this enzyme regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.Read moreRead less
Intervening In The Natural History Of Type 1 Diabetes: An Integrated Approach
Funder
National Health and Medical Research Council
Funding Amount
$9,466,000.00
Summary
This Program brings together four of Australia’s top type 1 diabetes clinical and lab-based research teams. The program has three intersecting themes. The first theme, pathogenesis, focuses on early life and understanding why type 1 diabetes develops. The second theme, prevention, seeks to identifying new drugs to stop the disease from occurring. The third theme, treatment, aims to improve therapies to replace the cells that are destroyed during the disease process.
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.
Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?
Funder
National Health and Medical Research Council
Funding Amount
$459,450.00
Summary
It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of ....It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.Read moreRead less
Regulation Of Protein Kinases And Their Substrates
Funder
National Health and Medical Research Council
Funding Amount
$582,000.00
Summary
Western communities are experiencing an obesity epidemic with up to half the population being overweight. Sedentary life styles and high caloric intake are the cause and will contribute to the development of age onset diseases including obesity, diabetes, cardiovascular disease, stroke and neurodegeneration. This project is investigating an enzyme that plays a pivotal role in controlling the body s response to exercise and diet. The key enzyme involved in this process is called the AMP-activated ....Western communities are experiencing an obesity epidemic with up to half the population being overweight. Sedentary life styles and high caloric intake are the cause and will contribute to the development of age onset diseases including obesity, diabetes, cardiovascular disease, stroke and neurodegeneration. This project is investigating an enzyme that plays a pivotal role in controlling the body s response to exercise and diet. The key enzyme involved in this process is called the AMP-activated protein kinase. This work will increase our understanding of the health benefits of diet and exercise. This new knowledge will play a vital role in developing new therapies for promoting exercise and mitigating the effects of diet that will improve health during the ageing process.Read moreRead less