Inositol Polyphosphate 1-phosphatase, A Novel Anti-hypertrophic Factor
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
Growth of the heart muscle cells occurs after heart attack and in people with high blood pressure or who suffer from diseases such as diabetes. Such growth leads eventually to the development of heart failure, a major cause of death and disability in western societies. We have identified a novel inhibitor of this growth, an enzyme that destroys a signalling intermediate called inositol(1,4)bisphosphate (or IP2). We now need to define how reduction in IP2 reduces growth and whether it provides a ....Growth of the heart muscle cells occurs after heart attack and in people with high blood pressure or who suffer from diseases such as diabetes. Such growth leads eventually to the development of heart failure, a major cause of death and disability in western societies. We have identified a novel inhibitor of this growth, an enzyme that destroys a signalling intermediate called inositol(1,4)bisphosphate (or IP2). We now need to define how reduction in IP2 reduces growth and whether it provides a useful target for therapy.Read moreRead less
GPI Anchored Forms Of The Dengue Virus NS1 Protein: Production And Role In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$203,448.00
Summary
Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we h ....Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we have identified. We plan to study the role that this protein plays in the more severe and often fatal forms of dengue infection (dengue haemorrhagic fever and dengue shock syndrome). In these more severe and life threatening forms of dengue the blood vessels of these patients become leaky. It is thought that this is caused by the secretion of certain chemicals (cytokines) from infected cells. We have shown that dengue infected human cells, which have the unusual form of NS1 protein on their surface, are capable of being activated by antibodies. Antibodies are proteins which are produced by the human body to fight infection. We aim to study whether cytokines are secreted from infected human blood cells activated in this way and whether these cytokines cause blood vessels to become leaky. We will also study how the virus produces this variant form of NS1 in the two host species that the virus infects; mosquito and human. These studies will increase our understanding of dengue virus infection and will provide valuable information concerning the role that this unusual form of the degue virus protein NS1 plays in the severe forms of dengue fever; dengue haemorrhagic fever and dengue shock syndrome.Read moreRead less
Ischaemia-induced Sarcolemmal Changes And Their Role In Ins(1,4,5)P3 Generation And Arrhythmogenesis
Funder
National Health and Medical Research Council
Funding Amount
$468,750.00
Summary
Studies in our laboratory at the Baker Heart Research Institute over the last several years have identified a novel mechanism causing the development of arrhythmias, a primary cause of sudden cardiac death in heart failure as well as during an acute heart attack caused by acutely reduced blood flow. The reduced blood flow leads to lowered oxygen and nutrients and thus the beating heart cells have insufficient energy to properly maintain function. Under these stressed conditions, cardiac myocytes ....Studies in our laboratory at the Baker Heart Research Institute over the last several years have identified a novel mechanism causing the development of arrhythmias, a primary cause of sudden cardiac death in heart failure as well as during an acute heart attack caused by acutely reduced blood flow. The reduced blood flow leads to lowered oxygen and nutrients and thus the beating heart cells have insufficient energy to properly maintain function. Under these stressed conditions, cardiac myocytes produce large amounts of a small molecule called IP3, which interferes with the normal electrical balance of the cells. Blocking IP3 generation prevents arrhythmias under these acutely ischaemic conditions. In more recent studies, we have identified many of the enzymes responsible for generation of IP3 in heart cells and have defined the properties of the regions of the cell responsible for this response. We now want to establish exactly how a period of ischaemia alters the localization or functioning of the enzymes that are responsible for this pathological change that leads to fatal arrhythmias.Read moreRead less
Intracellular Calcium Signalling And Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,357.00
Summary
The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat mal ....The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat malabsorption, and liver failure, the balance and regulation of calcium in liver cells is abnormal. The aims of the present experiments are to investigate the mechanisms by which hormones regulate the flow of calcium into liver cells. The experiments will involve the measurement of calcium in different regions of liver cells using fluorescent dyes and high resolution microscopy, and the identification of structural proteins and organelles within the liver cell which are required to control calcium inflow. The results should show how an important type of calcium channel in liver cells works and is controlled. This knowledge will allow better treatment of diabetes, fat malabsorption and liver failure. The knowledge should also lead to improvements in liver transplant operations.Read moreRead less