Identification Of Cardiac Sarcoplasmic Reticulum Targets For Cardiotoxic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$265,986.00
Summary
Anthracyclines are drugs which are used successfully in chemotherapy. Unfortunately, these drugs can lead to serious heart problems which sometimes result in death, and the mechanisms behind this remain elusive. Finding the specific targets of these drugs and how these drugs affect heart contraction may lead to designing drug cocktails which protect the heart from side effects.
Intracellular Calcium Signalling And Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,357.00
Summary
The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat mal ....The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat malabsorption, and liver failure, the balance and regulation of calcium in liver cells is abnormal. The aims of the present experiments are to investigate the mechanisms by which hormones regulate the flow of calcium into liver cells. The experiments will involve the measurement of calcium in different regions of liver cells using fluorescent dyes and high resolution microscopy, and the identification of structural proteins and organelles within the liver cell which are required to control calcium inflow. The results should show how an important type of calcium channel in liver cells works and is controlled. This knowledge will allow better treatment of diabetes, fat malabsorption and liver failure. The knowledge should also lead to improvements in liver transplant operations.Read moreRead less
Unique Isoform-specific Regulation Of Cardiac Ryanodine Receptors By Calcium Store Proteins
Funder
National Health and Medical Research Council
Funding Amount
$421,160.00
Summary
The importance of proteins that regulate calcium stores of heart muscle is graphically illustrated by massive changes in cell structure and function, which lead to ventricular fibrillation and fatality when the proteins are disrupted. We recently made the remarkable discovery that the proteins have a unique action in the heart which enhances cardiac contraction. We will discover the interaction sites between the proteins and will define novel therapeutic targets for heart failure.
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.
SPECIFIC MODIFICATION OF SKELETAL MUSCLE RYANODINE RECEPTOR ACTIVITY
Funder
National Health and Medical Research Council
Funding Amount
$411,000.00
Summary
The project will have implications for muscle fatigue, which is a public health issue in an aging population, and for neuromuscular diseases and muscle weakness. The ryanodine receptor (RyR) calcium release channel regulates changes in calcium concentrations inside the muscle cell that are essential for respiration and movement. Defects in expression of RyRs results in death in utero or at birth. The RyR is also important in many other tissues, where it acts either alone or in combination with a ....The project will have implications for muscle fatigue, which is a public health issue in an aging population, and for neuromuscular diseases and muscle weakness. The ryanodine receptor (RyR) calcium release channel regulates changes in calcium concentrations inside the muscle cell that are essential for respiration and movement. Defects in expression of RyRs results in death in utero or at birth. The RyR is also important in many other tissues, where it acts either alone or in combination with a second type of calcium channel, to regulate the changes in the concentrations of calcium ions within the cell, which are essential for a variety of processes including cardiac contraction, vascular constriction, neuronal activity and immune responses. Despite its importance, little is known about the regulation of the RyR channel opening during contraction in skeletal muscle or the mechanisms of ion movement through its pore. It is often difficult to define the specific role of RyRs in intact tissues because of the lack of specific probes for the channel. The RyR is an obvious target for therapeutic drugs to modify muscle contraction, but has not been used as such because of the lack of specific and reversible drugs. Muscle performance is reduced, and fatigue is rapid, in neuromuscular disease. Performance can be improved by variety of drugs like anabolic steroids which unfortunately have additional adverse actions. The aims of the project are (a) to discover more about the regulation of, and ion conduction pathway through, the skeletal muscle RyR channel, (b) to identify compounds that can be used as specific probes for RyR activity and (c) to identify compounds that might in the future provide the basis for development of the RyR as a therapeutic target.Read moreRead less