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Mechanisms Regulating Ribosomal Gene Transcription During Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$436,540.00
Summary
After birth the muscle cells of the human heart stop dividing. Subsequent growth of the heart is achieved by increasing the size of preexisting muscle cells. This process is referred to as hypertrophic growth and accounts for the difference in size between the juvenile and adult human heart. However later on in life, particularly during cardiovascular disease states such as high blood pressure, the adult heart may grow above and beyond that normally expected. This uncontrolled growth, results ev ....After birth the muscle cells of the human heart stop dividing. Subsequent growth of the heart is achieved by increasing the size of preexisting muscle cells. This process is referred to as hypertrophic growth and accounts for the difference in size between the juvenile and adult human heart. However later on in life, particularly during cardiovascular disease states such as high blood pressure, the adult heart may grow above and beyond that normally expected. This uncontrolled growth, results eventually in a sick heart which is no longer able to function properly. Such inappropriate growth of the heart is a component of many human cardiovascular disease states and contributes significantly to human morbidity and mortality. Regardless of the cause, hypertrophic growth of the heart results from increased protein synthesis. This is controlled by increased synthesis of ribosomes, the machinery responsible for making proteins. During the course of our studies investigating the regulation of heart muscle cell hypertrophy we have demonstrated that changes in the activity of a protein termed UBF, which is involved in regulating synthesis of ribosomes, correlates with the rate of hypertrophic growth. We have also demonstrated that if we artificially increase the amount of UBF protein in heart muscle cells we can stimulate hypertrophy. These finding indicate that alterations in the amount or activity of UBF may link hypertrophic stimuli to increased growth of the heart. The work described in this study proposes to investigate the signals and pathways which regulate the amount and activity of the UBF protein during hypertrophic growth of heart muscle cells. We hope by understanding the mechanisms by which the heart grows we will be able to design rational therapeutic regimens to combat the abnormal growth of the heart that often accompanies human cardiovascular disease states such as high blood pressure.Read moreRead less
Homeodomain Nkx2-5-dependent Negative Feedback Loop Important In Heart Development And Congenital Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,330,245.00
Summary
Congenital heart disease (CHD) is the cause of most deaths in children in the first year of life. We have identified a genetic pathway important for both normal cardiac development and CHD that involves the cardiac transcription factor Nkx2-5. This pathway controls a transition in embryos between cardiac cell specification and expansion. We will now explore the biochemical and genetic mechanisms underlying this pathway to help us understand CHD and identify its causative genes.
Regulation Of Cardiac Hypertrophy A At The Level Of Ribosome Biogenesis
Funder
National Health and Medical Research Council
Funding Amount
$634,587.00
Summary
A major feature of cardiac hypertrophy (enlarged heart) is accelerated cell growth and protein synthesis. This results from increased synthesis of ribosomes (the protein synthetic machinery). This study will examine a factor termed UBF whose activity is critical for the regulation of ribosome synthesis. Understanding the mechanisms controlling UBF function will provide new avenues in which to develop therapeutics to combat hypertrophic heart disease.
Determining Current And Future Populations At Risk Of Cardiovascular Disease Using Applied Geographic Information (GIS).
Funder
National Health and Medical Research Council
Funding Amount
$332,713.00
Summary
This unique and innovative project has the potential to deliver a powerful tool to both highlight and combat the burden of CVD in Australia. Key outcomes include,the ability to identify geographical ‘hotspots’ where there is likely to be a mismatch between demand for and actual provision of cardiovascular services and where new hotspots are likely to emerge requiring increased resources and services as a result of the ageing and increasing risk factors such as diabetes and obesity.
Alfred And Baker Medical Unit Centre For Clinical Cardiovascular Research
Funder
National Health and Medical Research Council
Funding Amount
$2,000,000.00
Summary
This Centre has three objectives: to create clinical research platforms; to provide time and training for advanced cardiology trainees, young clinical academics, research nurses, allied health staff and non-medical science graduates; and to translate previously established local and international research outcomes into knowledge, education and health benefits for the wider Australian community.
Atherosclerotic vascular disease cause considerable morbidity, mortality and use of health services in Australia. Current known risk factors explain approximately half of all cardiovascular diseases. The search for new risk factors is therefore a high priority. Evidence suggests that chronic inflammation is closely involved in the process of atherosclerosis and its clinical complications. This study aims to determine if sensitive serum markers of inflammation and gene-environment interactions th ....Atherosclerotic vascular disease cause considerable morbidity, mortality and use of health services in Australia. Current known risk factors explain approximately half of all cardiovascular diseases. The search for new risk factors is therefore a high priority. Evidence suggests that chronic inflammation is closely involved in the process of atherosclerosis and its clinical complications. This study aims to determine if sensitive serum markers of inflammation and gene-environment interactions that affect inflammation will predict the extent and progression of carotid atherosclerosis in an Aboriginal and a non Aboriginal community population and in patients with premature coronary heart disease. This study should provide a greater understanding of the mechanisms involved in the development and progression of atherosclerosis. It is likely that we will find that some inflammatory markers and candidate gene polymorphisms will help identify individuals at increased cardiovascular risk, and who require earlier treatment to prevent disease. In particular, it would focus on preventive therapies that reduce atherosclerosis through anti-inflammatory targets. This study represents a crucial step towards improving our understanding of the aetiology of cardiovascular diseases, and in developing new ways to prevent heart disease and stroke. Progress in these areas will likely have significant public health benefitsRead moreRead less
Neurogenic Mechanisms Of Cardiovascular Risk In The Metabolic Syndrome: Benefits Of Lifestyle Interventions
Funder
National Health and Medical Research Council
Funding Amount
$328,194.00
Summary
One in four adult Australians has the 'metabolic syndrome' (MetS), a clustering of metabolic and heart disease risk factors associated with abdominal obesity. Sympathetic nervous system (SNS) activity is increased in the MetS resulting in enhanced release of the stress hormone 'noradrenaline' . This project will examine the biological and genetic determinants of enhanced SNS activity and the benefits of lifestyle interventions (weight loss, weight loss maintenance and aerobic exercise).
I am a biomedical research scientist. My research has examined effects of diet and lifestyle on cardiovascular risk factors, including aspects of diabetes, hypertension and atherosclerosis. My research has focused on the potential beneficial effects of om
Developmental Stages Of Cardiovascular Risk Factors And Their Public Health Impact: A Life Course Perspective
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Using a life course approach, the aims of this study are to (a) investigate the developmental stages (pre-natal, childhood and adolescence) of cardiovascular (CVD) risk factors in young adulthood; (b) identify what is influencing these developmental stages either directly or indirectly and (c) quantify the public health burden of these stages and individual factors. Findings will enhance our understanding of the developmental stages of CVD and their public health burden.