C-Jun N-terminal Kinase Actions In The Response To Stress
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
All cells in our body sense and respond to stressful changes in our environment. We are focused on enzymes called JNKs that relay this information, and so form part of the key response pathways. JNKs are now being evaluated as new drug targets for the treatment of diseases including diabetes and stroke, but we know very little about how JNKs work in stressed cells. We will define new partners for the JNKs and in so doing reveal new information on the stress-activated events they regulate.
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.
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
Many of the most serious diseases of Western societies including obesity, Type 2 diabetes, cancer growth and metastasis and cardiovascular disease have metabolic dimensions. The enzyme AMPK regulates cellular and whole body energy homeostasis by coordinating metabolic pathways to balance energy demand with nutrient supply. We are studying the structure and function of AMPK with the aim of better treating metabolic diseases.
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.
Cytokine Signalling And Insulin Resistance In Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
Western communities are experiencing an epidemic of obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating why being overweight and obese causes diabetes. Improved understanding about how hormones 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.
Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
An Integrated Systems Biology Approach For The Development Of New Therapeutic Strategies For The Treatment Of High Grade Glioma
Funder
National Health and Medical Research Council
Funding Amount
$696,404.00
Summary
Glioma, the most common adult brain cancer, is incurable. Recent advances now allow us to grow glioma cells directly from patients in the laboratory in a way that preserves the features of the original tumor. In this proposal we will systematically analyze such cells using state-of-the-art technologies to identify new processes important to glioma, which in turn should facilitate the identification of innovative therapeutic approaches.
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
Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.