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.
Store Operated Ca2+ Entry In Skeletal Fibres From Normal And Dystrophin-deficient Muscle.
Funder
National Health and Medical Research Council
Funding Amount
$351,790.00
Summary
Skeletal muscle, the most abundant tissue in the body, is essential for life and movement. Muscle function is regulated in a complex manner by calcium and is severely impaired in patients with Duchenne muscular dystrophy. Changes in calcium regulation, known to occur in dystrophic muscle, will be investigated in an animal model using a novel, single cell approach. Results obtained will contribute to understanding better muscular dystrophy and help provide therapeutic targets for treatment.
STIM1 And Orai1 Proteins In Store-operated Calcium Entry In Liver
Funder
National Health and Medical Research Council
Funding Amount
$516,552.00
Summary
The liver plays a central role in controlling vital functions of the body. Changes in calcium level in the liver cells regulate most their functions, including fat and carbohydrate metabolism. There is ample evidence that suggests that diseases such as fatty liver and cholestasis affect the control of calcium in the liver. This research will investigate the mechanisms of calcium homeostasis in the liver and provide information for development of new approaches for treating liver disease.
Rhythmicity And Synchronicity In Uterine Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$291,823.00
Summary
Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that ....Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that rhythmicity and synchronicity of uterine contractions are underpinned by store pacemaking. Second, we will probe the role of current spread between cells via gap junctions as a mechanism of recruitment and will examine whether accessory cells termed interstitial cells subserve a role in pacemaking. These cells are present within the uterine wall but their function is unknown. We will probe their ion channel properties in relation to pacemaking using patch clamp techniques. Third, we will examine the role of labour hormones, such as oxytocin, in augmenting uterine contractions via interaction with the Ca2+ store mechanism and cell recruitment. These studies will provide new and fundamental insights into uterine pacemaking, an outcome that should be of great significance to understanding and better controlling birth-associated complications such as preterm delivery and failure to progress.Read moreRead less
Control Of Uterine Contraction: Role Of Interstitial Cells
Funder
National Health and Medical Research Council
Funding Amount
$587,206.00
Summary
Being born premature may increase risk of below average IQ, poor performance at school and behavioural difficulties in the child, and increased obesity and blood pressure as an adult, predisposing to life long socio-economic disadvantage. We have come up with a new approach to understanding the control of uterine contraction, namely, that cells other than muscle cells, recently identified in the uterine wall, are essential for inducing forceful and orderly muscle cell contraction during labour.
Regulation Of Nuclear Calcium Concentration In The Life Or Death Of Cells
Funder
National Health and Medical Research Council
Funding Amount
$195,047.00
Summary
The nucleus is the most prominent of all cell organelles and contains the primary genetic material for cellular development and growth. It performs some of the most important functions in the life and death of all living cells. However, little is known about many of the regulatory signals and events that control nuclear function. We will use new genetically-encoded sensor molecules that a living cell can be instructed to produce at various internal locations to explore important features of cell ....The nucleus is the most prominent of all cell organelles and contains the primary genetic material for cellular development and growth. It performs some of the most important functions in the life and death of all living cells. However, little is known about many of the regulatory signals and events that control nuclear function. We will use new genetically-encoded sensor molecules that a living cell can be instructed to produce at various internal locations to explore important features of cell control. This study will look specifically at how changes in the concentration of ionised Ca2+ in the nucleus control the switching on of genes and the initiation of programmed cell death pathways. This information is of significance to our understanding of normal cell growth and development, as well as abnormal growth (e.g. cancer).Read moreRead less