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 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.
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
Examining the links between obesity and insulin resistance. Obesity prevalence is rapidly increasing in Australia and contributes to the onset of many chronic diseases, such as diabetes, heart disease and cancer. This project will examine how obesity contributes to disease risk and how modifying nutrient delivery and other interventions that protect from cellular stress reduces these risks.
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
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
Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiol ....Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiology and molecular biology we expect to answer a fundamental question how STIM and Orai proteins interact to form functional store-operated calcium channels, and how the expression of STIM and Orai is regulated.Read moreRead less
Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount ....Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount before we can understand and develop treatments for dealing with heart problems. This information will facilitate the development of techniques to treat and prevent heart rhythm disorders that are a common cause of morbidity in the community.Read moreRead less
Do depolarizing currents in the endothelium evoke contraction of vascular smooth muscle? Establishment of our concept involving a novel constricting influence in blood vessels will have two major benefits. First, it will keep Australian research at the leading edge in blood vessel research and thus maintain a very high international profile for Australian science. Second, our concept represents a whole new field of therapeutic potential for treating a range of vascular diseases involving excess ....Do depolarizing currents in the endothelium evoke contraction of vascular smooth muscle? Establishment of our concept involving a novel constricting influence in blood vessels will have two major benefits. First, it will keep Australian research at the leading edge in blood vessel research and thus maintain a very high international profile for Australian science. Second, our concept represents a whole new field of therapeutic potential for treating a range of vascular diseases involving excessive constriction of blood vessels. The development and manufacture of drugs in Australia would contribute to the national economy, and their consumption could improve the quality of life for those suffering from vascular diseases amenable to treatment by such drugs, likely to include pre-eclampsia, diabetes, hypertension.
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