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.
Two Recently Identified Calcium Transporters In Lactation And During Mammary Epithelial Cell Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$465,115.00
Summary
The transport of calcium into milk is a key event in human health. In addition to its importance in neonatal nutrition, the way breast cells regulate calcium also has implications in breast cancer, as well as the modification of proteins important in immunity, and the activity of biopharmaceuticals. This grant will determine how two specific calcium transporters regulate calcium levels in the breast and their respective roles in cellular processes important in normal function and in disease.
This project will test the proposal that rising follicle-stimulating hormone (FSH) levels in ageing females directly accelerate reproductive failure and bone loss , major public health issues due to delayed childbearing and our rising ageing population. We have developed a unique mouse model with elevated FSH levels that cause premature female infertility. We will now use this model to determine the direct effects of high FSH upon ovarian and uterine function, as well as bone loss with age.
The Effect Of Ischaemia And Reperfusion On Sarcoplasmic Reticulum Calcium Handling In The Heart
Funder
National Health and Medical Research Council
Funding Amount
$236,208.00
Summary
Ischaemic heart disease is one of the most common causes of premature death in our society. Ischaemia occurs when the blood flow to the heart is obstructed so that oxygen cannot get to the muscle cells and metabolic waste products cannot be washed away. During ischaemia the concentration of free calcium within a cardiac muscle cell increases, and when blood flow is returned to the muscle this calcium concentration can increase further to very high levels. It is this change in calcium that is res ....Ischaemic heart disease is one of the most common causes of premature death in our society. Ischaemia occurs when the blood flow to the heart is obstructed so that oxygen cannot get to the muscle cells and metabolic waste products cannot be washed away. During ischaemia the concentration of free calcium within a cardiac muscle cell increases, and when blood flow is returned to the muscle this calcium concentration can increase further to very high levels. It is this change in calcium that is responsible for the reduced muscle force and abnormal cardiac rhythm that are the main cause of death. Cardiac muscle cells contain an intracellular compartment called the sarcoplasmic reticulum (SR). Under normal conditions the SR stores large amounts of calcium in order to maintain a low concentration of calcium free within the cell. However, even in a resting cell, calcium can escape from the SR through channels in SR membrane. We are using a state-of-the-art microscope to visualize these tiny packets of calcium, termed calcium sparks, as they travel through the SR membrane. If the number of calcium sparks increases, the amount of calcium being released from the SR also increases. We are studying what happens to calcium sparks, and therefore SR calcium release, during ischaemic heart disease. We are also examining the effect of ischaemic heart disease on the concentration of calcium within the SR and the activity of the transporters that pump calcium back into the SR. We hope to show that a change in the way the SR regulates calcium contributes to ischaemic damage. Understanding how changes in SR function alter muscle force and cardiac rhythm will help in the development of drugs to protect against ischaemic damage.Read moreRead less
The Role Of The Cytoskeleton In Communication Between The L-type Ca2+ Channel And The Mitochondria In Cardiac Pathology
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
The L-type calcium channel is a protein in the membrane of heart muscle cells responsible for maintaining normal rhythm and contraction. We have shown that the channel can also regulate the function of the energy producing part of the cell (mitochondria). This occurs with the assistance of proteins that maintain cell architecture. We will test whether this association is altered in human disease where the cell architecture is disrupted to determine the mechanisms for poor energy supply.