The role of intracellular calcium in fibre-type specific gene expression in skeletal muscle. Muscles contain different fibre types whose composition can be changed by activity. The aim of this proposal is to identify the intracellular mechanisms which control fibre type. Our hypothesis is that different patterns of intracellular calcium determine the pattern of gene expression which determines fibre type. Understanding how gene expression is regulated is a central issue in biology.
Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old musc ....Modulating the molecular and cellular physiology of ageing skeletal muscle. Understanding the underlying mechanisms of how ageing affects muscle is of increasing importance to the community as the number of older persons in the population continues to escalate and the age of retirement increases. Old muscles are slower and weaker than young muscles, and are more easily injured. This proposal is focussed on developing safe therapies to prevent or reverse these age-related effects. Making old muscles young again, is a research strategy that will promote healthy ageing and enable older Australians to enjoy a better quality of life.Read moreRead less
The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to ....The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to controlling or modifying their function.Read moreRead less
Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the de ....Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the design of novel compounds for treating muscle disorders in animals and humans, for improving meat quality and for use as insecticides. The project will facilitate graduate and undergraduate training in basic science with exposure to biotechnology, through our commercial partner Biotron.Read moreRead less
Is The Role Of IL6 In Metabolism Dependent On Its Cellular Origin?
Funder
National Health and Medical Research Council
Funding Amount
$714,061.00
Summary
Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development f ....Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development for type 2 diabetes.Read moreRead less
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the ....How tissues generate the peptide hormone angiotensin II. This project aims to investigate how local tissue renin-angiotensin systems operate. A blood-borne renin–angiotensin system (RAS) produces a peptide (AngII) to control blood pressure, and fluid/salt balance. Many tissues, such as the brain and heart, also possess an independent, tissue RAS, but how these function is not well understood. The project will use a model whereby infiltrating macrophages (following damage to the heart) drive the activation of this system to trigger the local generation of AngII. This project addresses the question of where exactly in the heart the RAS components are turned on, how they interact to generate AngII and whether the activation of the local RAS is beneficial or not to cardiac function. The findings should provide critical insights into an important hormonal system.Read moreRead less
Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine ....Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine the importance of a family of intracellular signalling enzymes, the Class II phosphoinositide 3-kinases, in platelet function. These studies will define the contribution of these enzymes to platelet production and function and will establish whether their inhibition is an attractive strategy for the prevention of arterial thrombosis.Read moreRead less
Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence micro ....Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence microscopy and digital imaging technologies for studying multicellular tissues such as skeletal muscle will enhance the international competitiveness of Australian biological research. The research will optimise development of gene delivery systems that may find eventual application for muscle wasting disorders and conditions where muscle weakness compromises quality of life.Read moreRead less