The Plasmalemmal Calcium Pump And Vascular Smooth Muscle Cell Proliferation.
Funder
National Health and Medical Research Council
Funding Amount
$179,593.00
Summary
Excessive growth of smooth muscle cells can lead to adverse effects in our arteries. The level of calcium inside the muscle cells that line our arteries appears to regulate their growth. In these studies we will assess the changes in the synthesis (expression) of a pump which removes calcium from cells. We will also characterise the effects of modifiers of cell growth on the expression of the calcium pump. The effect of directly inhibiting the production of the calcium pump, on the growth of smo ....Excessive growth of smooth muscle cells can lead to adverse effects in our arteries. The level of calcium inside the muscle cells that line our arteries appears to regulate their growth. In these studies we will assess the changes in the synthesis (expression) of a pump which removes calcium from cells. We will also characterise the effects of modifiers of cell growth on the expression of the calcium pump. The effect of directly inhibiting the production of the calcium pump, on the growth of smooth muscle cells and the regulation of calcium will be determined for the first time.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.
Primary Cardiac Hypertrophy - A Functional Genetic Approach To Investigate Cellular Mechanisms Of Metabolic Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$226,692.00
Summary
Population studies have recently shown that enlargement of the heart, even when blood pressure is normal, is a risk factor which can lead to cardiovascular complications. Very little is known about the alterations in heart cell structure and function which occur in cardiac enlargement not complicated by high blood pressure. It is possible that specific metabolic abnormalities underlie this condition. The goal of this study is to use a newly developed genetically manipulated experimental animal m ....Population studies have recently shown that enlargement of the heart, even when blood pressure is normal, is a risk factor which can lead to cardiovascular complications. Very little is known about the alterations in heart cell structure and function which occur in cardiac enlargement not complicated by high blood pressure. It is possible that specific metabolic abnormalities underlie this condition. The goal of this study is to use a newly developed genetically manipulated experimental animal model to study the function of single heart cells. In this model one of the glucose transporters has been deleted. Our goal is to compare heart function in this genetic model with heart function in diabetes. Cells are isolated from hearts using enzyme treatments and investigated microscopically to determine if there are subcellular structural alterations. Functional studies are performed on individual viable cells using a combination of electrical recording techniques and fluorescence imaging methods. The experimental aim is to assess whether there is disruption of sodium, calcium or pH regulation associated with cardiac enlargement associated with metabolic abnormalities. This research will assist in identifying appropriate therapeutic strategies for intervention in the treatment or prevention of conditions associated with cardiac enlargement.Read moreRead less
L-amino Acid Sensing By The Extracellular Calcium-sensing Receptor: Molecular, Cellular And In Vivo Studies
Funder
National Health and Medical Research Council
Funding Amount
$362,545.00
Summary
Recent work by Dr Conigrave and colleagues demonstrates for the first time that protein and calcium metabolism are linked at the molecular level by the widely distributed calcium-sensing receptor. The project will aim to demonstrate the physiological significance of this finding by testing whether L-amino acids, the building blocks of body protein, exert receptor-dependent control over the secretion and blood levels of hormones that regulate body calcium levels. It will further test the hypothes ....Recent work by Dr Conigrave and colleagues demonstrates for the first time that protein and calcium metabolism are linked at the molecular level by the widely distributed calcium-sensing receptor. The project will aim to demonstrate the physiological significance of this finding by testing whether L-amino acids, the building blocks of body protein, exert receptor-dependent control over the secretion and blood levels of hormones that regulate body calcium levels. It will further test the hypothesis by determining whether amino acids exert receptor-dependent control over the proliferation of bone forming cells and urinary excretion of calcium.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