Mechanisms Involved In Reduced Cardiac Contractility As A Consequence Of Growth Restriction During Fetal Development
Funder
National Health and Medical Research Council
Funding Amount
$317,810.00
Summary
Functional development of the heart muscle has been a focus of intense research over the last 40 years. Despite our current understanding of the changes in how excitation of the cardiomyocyte leads to contraction, a process broadly termed excitation-contrcation (E-C) coupling, a major model used to study paralells of human fetal development, the sheep, has not been examined in this context. As such, it remains unclear how E-C coupling evolves from the fetus to the adult. Understanding normal phy ....Functional development of the heart muscle has been a focus of intense research over the last 40 years. Despite our current understanding of the changes in how excitation of the cardiomyocyte leads to contraction, a process broadly termed excitation-contrcation (E-C) coupling, a major model used to study paralells of human fetal development, the sheep, has not been examined in this context. As such, it remains unclear how E-C coupling evolves from the fetus to the adult. Understanding normal physiology is imperative to subsequetly understand pathological states, such as interuterine growth restriction (IUGR). In Australia, the incidence of IUGR leading to low birth weight babies is 7%. IUGR is caused by maternal undernutrition, maternal smoking-drug use and placental insufficiency. It is associated with an increase in perinatal mortality, respiratory problems, SIDS and morbidity. Epidemiological studies show that low birth weight babies are also at an increased risk of cardiovascular disease, including heart failure, in adult life. To date, there is little information on the impact of fetal growth restriction on the normal development and function of the heart muscle. Understanding the impact of IUGR on heart muscle development will allow the elucidation of the underlying physiological mechanisms linking these two temporally distinct events. This mechanistic understanding will allow improved clinical management of those individuals at risk of cardiovascular disease in adult life arising from IUGR. It may also allow for early intervention strategies that can improve cardiovascular function. Therefore, we propose to examine both the normal developmental changes to E-C coupling so that we can understand how placental insufficiency leading to IUGR impairs normal heart muscle development. This will result in impaired function at a cellular level, which will ultimately manifest as an increased susceptibility of the heart to injury in later life.Read moreRead less
The Effect Of Dietary Fatty Acids On Cellular Calcium Handling Mechanisms In Cardiac Muscle
Funder
National Health and Medical Research Council
Funding Amount
$275,765.00
Summary
A major health problem in the developed countries is cardiovascular disease, which is manifest as high blood pressure, stroke, heart attack and abnormalities of heart rhythm, or cardiac arrhythmias. A western diet, ie. one high in animal fat, or saturated fats, may be to blame. Human epidemiological studies have shown that consumption of a diet high in saturated fats is correlated with a propensity to arrhythmias while a diet high in polyunsaturated fatty acids (PUFAs) can confer protection from ....A major health problem in the developed countries is cardiovascular disease, which is manifest as high blood pressure, stroke, heart attack and abnormalities of heart rhythm, or cardiac arrhythmias. A western diet, ie. one high in animal fat, or saturated fats, may be to blame. Human epidemiological studies have shown that consumption of a diet high in saturated fats is correlated with a propensity to arrhythmias while a diet high in polyunsaturated fatty acids (PUFAs) can confer protection from coronary heart disease and cardiac arrhythmias. The mechanisms underlying these effects are not fully understood. The contraction of the heart depends on changes in calcium inside the individual muscle cells. Abnormalities of the way calcium is handled in the cells leads to abnormalities of contraction and to a certain types of arrhythmia. Over the last 5 to 10 years, technological developments have enabled us to examine changes in calcium in living heart cells at microscopic level. It is possible to fill individual living cells with a fluorescent dye which changes either the magnitude or the wavelength of its fluorescence according to the ambient calcium concentration. Cells filled with these dyes are examined with a laser scanning confocal microscope, in which a very tightly focussed laser beam excites the dye and the resulting fluorescence is gathered by a computer controlled image analysis system. In this way we can measure the calcium concentration within the cells with a spatial resolution of about 1-1000 of a millimetre, and a time resolution of about 1-100 of a second. Using these techniques, we have found that supplementing the diet of rats with either PUFAs or saturated fats produces a dramatic change in the way that calcium is stored and released in their heart cells. This effect of dietary fats has not been reported before, and it may represent an important clue as to how these substances protect against many cardiac arrhythmias.Read moreRead less
Assessment Of Calcium Signaling In Breast Cancer Cells Associated With Epithelial-mesenchymal Transition
Funder
National Health and Medical Research Council
Funding Amount
$116,762.00
Summary
This research will assess the role of specific proteins that control cell function in a process which is important in the spread of cancer cells throughout the body. The work is aimed at identifying new targets for drugs that may be used to prevent or stop the spread of breast cancer cells to other organs such as the brain and liver.
Calcium acts as a signal to control cell processes important in cancer. The entry of calcium into the cell is regulated by calcium channels and we have found some channels are over-expressed in breast cancer. Altering the expression and activity of these calcium channels is a possible therapeutic approach for cancer. We will determine the reasons and consequences of alterations of calcium channels in breast cancer and whether they are viable anti-cancer therapies and biomarkers.
Modelling of Bypass Pneumatic Conveying Systems. Many of the physical items we use in our daily lives have at some point required transport and handling as powdered or granular materials during the manufacturing process. Be it food (sugar, flour), chemicals (soap powders, detergents) or power generation (coal and ash); each of these industries uses the flexibility of pipelines as a transport mechanism. However, not all materials will convey reliably in conventional pipelines. This project will ....Modelling of Bypass Pneumatic Conveying Systems. Many of the physical items we use in our daily lives have at some point required transport and handling as powdered or granular materials during the manufacturing process. Be it food (sugar, flour), chemicals (soap powders, detergents) or power generation (coal and ash); each of these industries uses the flexibility of pipelines as a transport mechanism. However, not all materials will convey reliably in conventional pipelines. This project will provide the fundamental understanding of how bypass systems can overcome this problem by conditioning the material along the pipeline length. The results will lead to better pipeline design outcomes that will ultimately expand the use of the cost effective process of pneumatic pipeline conveying. Read moreRead less
Efficient Strategies for Coordinating Autonomous Vehicles for Maximising Australia's Waterfront Productivity. This project will lift the productivity of container terminals by enabling the effective deployment of autonomous vehicles in large numbers. The project outcomes of practically deployable and scalable algorithms, realised as live software, will significantly enhance Patrick Stevedores Holdings' world leading technology and the potential of such automation systems to revolutionise materia ....Efficient Strategies for Coordinating Autonomous Vehicles for Maximising Australia's Waterfront Productivity. This project will lift the productivity of container terminals by enabling the effective deployment of autonomous vehicles in large numbers. The project outcomes of practically deployable and scalable algorithms, realised as live software, will significantly enhance Patrick Stevedores Holdings' world leading technology and the potential of such automation systems to revolutionise material handling around the globe. Beyond the benefits of technology commercialisation, the project will also benefit Australia economically through extending its leading role in developing autonomous systems for material handling, enhancing the frontier technologies for building Australian industries, and alleviating looming capacity constraints.Read moreRead less