Characterisation And Regulation Of Chloride Channels In Cardiac And Skeletal Sarcoplasmic Reticulum In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$381,856.00
Summary
An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe ....An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe arrythmia or cardiac arrest. The objective is to understand channel involvement in the mechanisms underlying the function of cardiac and skeletal muscle. We believe that by mimicking the factors that occur in pathological conditions we can understand how ion channels are altered and controlled, and find ways of reversing harmful alterations, thereby reversing cell damage and failure of vital muscle function.Drugs will be used to modify the 'gating' of the channels. By comparing the effects of different drugs, we hope to determine the important features of the mechanisms that control the gating of the channels, making them more or less sensitive to different influences, especially those that occur in pathological states. The study has great application to the study of other pathologies, e.g. cystic fibrosis, severe diarrhoea, paralysis and chronic fatigue. The pharmacological emphasis offers the fundamental science needed to design novel and specific drugs to combat the many serious pathologies related to ion channel effects. Aside from its importance to basic science and to immediate issues of health, the study offers considerable economic gains, both through improved public health and through development of pharmaceuticals.Read moreRead less
Biomarkers For Risk And Outcomes Of Type 2 Diabetes: A Discovery And Validation Approach In Australian And Chinese Subjects
Funder
National Health and Medical Research Council
Funding Amount
$599,489.00
Summary
The aim is to make better outcomes for people with Type 2 diabetes in Australia and China, by exploring various tests to improve prediction of diabetes progression, complication risk and treatment response. The team has data and samples from the Fenofibrate Intervention and Event Lowering in Diabetes Trial and from the Shanghai Diabetes Study. This approach is very time and cost-effective. We will also study animal models to understand mechanisms of diabetes damage, and test new treatments.
Growth Regulatory Transcriptional Networks And Novel Therapies In Vascular Pathobiology
Funder
National Health and Medical Research Council
Funding Amount
$576,760.00
Summary
Cardiovascular disease and cancer together account for the majority of all deaths. Underpinning both these conditions are cellular and molecular changes in our blood vessels. This Fellowship will enable Professor Khachigian to enhance our understanding of fundamental mechanisms regulating the pathogenesis of vascular disease, and by harnessing this new knowledge in preclinical and human trials, generate novel strategies to combat a range of diseases through strategic partnership, collaboration a ....Cardiovascular disease and cancer together account for the majority of all deaths. Underpinning both these conditions are cellular and molecular changes in our blood vessels. This Fellowship will enable Professor Khachigian to enhance our understanding of fundamental mechanisms regulating the pathogenesis of vascular disease, and by harnessing this new knowledge in preclinical and human trials, generate novel strategies to combat a range of diseases through strategic partnership, collaboration and training.Read moreRead less
Determining The Cellular Mechanisms Involved In The Airway Response To Topical Citrate
Funder
National Health and Medical Research Council
Funding Amount
$444,491.00
Summary
The air passages of the lungs are lined by mucous membranes. These membranes are covered by a thin layer of fluid to protect the airways from drying. This fluid allows the cilia, the hair like projections on top of the airway cells to beat more effectively to remove mucous and inhaled particles from the lungs. The volume and composition of this fluid is determined by the salt and water movement across the mucous membranes of the airways. These processes are abnormal in cystic fibrosis (CF), the ....The air passages of the lungs are lined by mucous membranes. These membranes are covered by a thin layer of fluid to protect the airways from drying. This fluid allows the cilia, the hair like projections on top of the airway cells to beat more effectively to remove mucous and inhaled particles from the lungs. The volume and composition of this fluid is determined by the salt and water movement across the mucous membranes of the airways. These processes are abnormal in cystic fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, an abnormal gene disrupts one of the major mechanisms for salt and water movement in the air passages. This abnormal salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airways with repeated bacterial infections damaging the lungs. Over the last 10 years, we have developed a series of simple tests to measure the abnormalities in the CF airway of human subjects. We have isolated an exciting new clinical application for sodium citrate, a substance used in blood transfusions. Citrate appears to alter both the salt transport abnormalities found in CF. This research proposal seeks to better understand the dual effects of citrate and to test similar compounds that may have stronger effects. The ultimate aim of our research is to have sufficient knowledge to work out the best way to develop a new treatment for CF.Read moreRead less
Viral Therapy For Skeletal Muscle Alpha-actin Disease And Discovery Of Novel Neuromuscular Disease Genes And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$324,028.00
Summary
This research project is the next logical step towards treating patients with skeletal muscle actin disease - using viral delivery of normal actin genes in animal models of actin disease. Another arm of this project is to investigate the genetics and mechanisms causing two very different groups of muscle disorders in the Australian population: devastating muscle weakness in the foetal akinesias and enhanced muscle strength and bulk in individuals with strongman syndromes.
Preclinical Testing Of 3 Cysteine-related Drugs For Reducing Dystropathology In The Mdx Mouse Model Of Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$378,564.00
Summary
Duchenne muscular dystrophy (DMD) is devastating disease that affects young boys. We propose testing 3 cysteine related drugs which show promise in ameliorating the severity of the disease. The drugs are of particular interest because they are relatively inexpensive, can be taken orally, have few side effects and are already approved for human use. These drugs will tested in an animal model of DMD to test their efficacy.
The Role Of The Systemic Milieu In Preventing Motor Unit Remodelling And Loss During Ageing
Funder
National Health and Medical Research Council
Summary
Motor unit remodeling and loss contributes to the decline in muscle mass, strength and quality of life in our aging population. Recent data shows that exposing aged mice to 'blood-borne factors' from the circulation of a young mouse can reverse the age-associated deficits in motor unit structure and function. A better understanding of the factors controlling these anti-aging effects will be vital for finding new compounds to reverse the aging process and improve quality of life.