Mammalian cells have developed a complex signalling network responsible for monitoring and responding to changes in the levels of growth factors and the availability of nutrients, energy and oxygen in their environment. Deregulation of this network often results in uncontrolled cell growth and diseases including cardiac hypertrophy and cancer. This proposal aims to understand how this network controls cell growth and identify potential targets for diseases driven by uncontrolled growth.
Identifying The Critical Components Of Growth Factor-mediated Survival Pathways
Funder
National Health and Medical Research Council
Funding Amount
$589,338.00
Summary
The regulation of cell lifespan (cell survival) is controlled by growth factors and lies at the heart of all biological processes. However, little is known of the molecular switches inside cells that either turn survival on or off. We propose to identify and characterize the molecular switches inside cells that control the balance between cell survival and death. Targeting specific components of these switches may provide new approaches for the treatment of cancer and infectious diseases.
Adaptations of plant mitochondria during cold acclimation in Arabidopsis thaliana: towards an understanding of plant cold acclimation. Frost damage is a major cost to agricultural producers and some crop plant species needlessly adapt to cold, when they are grown in temperate regions or in glasshouses, which leads to decreased production. The principal outcome of this project will be to greatly extend our knowledge about plant mitochondrial responses to environmental cold stress and what role th ....Adaptations of plant mitochondria during cold acclimation in Arabidopsis thaliana: towards an understanding of plant cold acclimation. Frost damage is a major cost to agricultural producers and some crop plant species needlessly adapt to cold, when they are grown in temperate regions or in glasshouses, which leads to decreased production. The principal outcome of this project will be to greatly extend our knowledge about plant mitochondrial responses to environmental cold stress and what role they have in helping plants adapt to environmental change. An understanding of cold acclimation may allow the production of plants with altered cold acclimation phenotypes and greater frost tolerance.Read moreRead less
Apoptosis is a fundamental mechanism in regulating normal development and preventing cancer. Cancer cells must avoid apoptosis and also adapt to harsh metabolic environments in order to survive in the absence of effective nutrient supply and to resist the action of certain drugs. This project will provide a detailed analysis of metabolic changes allowing cells to survive long periods when the apoptotic process is absent and nutrients are limiting.
NOVEL REGULATORS OF CONNECTIVE TISSUE GROWTH FACTOR EXPRESSION AND BIOACTIVITY IN DIABETIC COMPLICATIONS
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Diabetes mellitus is common in our community. It causes much premature death and loss of quality of life. Recent data from Australian studies show that ~7% of adults over 25 years, and ~20% of people aged over 65 have diabetes, and diabetes in both children and adults is increasing in Australia. A critical problem caused by diabetes, irrespective of its cause, is that blood glucose levels are higher than normal. High blood glucose contributes to much of the damage to body tissues and to the earl ....Diabetes mellitus is common in our community. It causes much premature death and loss of quality of life. Recent data from Australian studies show that ~7% of adults over 25 years, and ~20% of people aged over 65 have diabetes, and diabetes in both children and adults is increasing in Australia. A critical problem caused by diabetes, irrespective of its cause, is that blood glucose levels are higher than normal. High blood glucose contributes to much of the damage to body tissues and to the early death that can occur in diabetes. Unfortunately, given our current treatment methods, in only a small number of patients can glucose levels in the body be consistently controlled into the normal range. How does high blood glucose cause damage to the body and its different tissues? This is a complex process. One way that damage occurs is through an increase in some of the growth factors in the body. In diabetes, high blood glucose can increase the production of some growth factors in an uncontrolled way. In turn, these growth factors then cause tissue damage. One of the growth factors that can be increased by the high glucose in diabetes is called connective tissue growth factor, or CTGF. CTGF can cause scars to form in tissues, and it is increased in diabetes in humans. Through NHMRC sponsored post-doctoral research over the past four years, Dr Twigg has published findings showing pathways by which diabetes causes increases in CTGF, and ways in which CTGF then causes tissue scarring. The current grant proposal presents new data showing further novel pathways by which CTGF is activated by diabetes and ways in which CTGF causes scarring. The pathways involved will be studied in detail in the project. In addition, methods to block CTGF and its harmful effects in diabetes will be developed in this work. By controlling CTGF, it is envisaged that damage to tissues will be reduced, leading to improved quality and quantity of life for people who have diabetes.Read moreRead less
Matching Supply And Demand: How Does Metabolism Fine-tune Signal Transduction?
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Insulin controls nutrient traffic and disrupting its actions are linked to many diseases: type 2 diabetes, cancer, heart disease. Here, I will test a novel hypothesis that our cells’ metabolic rate, defined by the balance between nutrient supply and energy expenditure, controls how cells respond to insulin. These metabolic regulatory nodes would play a major determinant of many essential functions linked to human health, and thus provide novel therapeutic targets for numerous diseases.
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.Read moreRead less
Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. ....Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. Understanding fat breakdown is also important for developing new processing technologies in the food industry.Read moreRead less
Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be dev ....Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be developed that will ultimately reduce the incidence of type 2 diabetes, and ease the associated financial burden on the community and healthcare system.Read moreRead less