Nutrient Dependent Signalling In Bone Via Calcium Sensing Receptors
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
Osteoporosis is a major health problem that affects as many as 10% of the Australian Community and costs the health budget millions of dollars each year. A number of key nutritional factors including calcium and dietary protein intake are known to be important in the development of osteoporosis. This proposal will test the hypothesis that human bone cells express a protein which senses calcium and amino acids, the calcium-sensing receptor, and thereby respond to nuritional signals arising from t ....Osteoporosis is a major health problem that affects as many as 10% of the Australian Community and costs the health budget millions of dollars each year. A number of key nutritional factors including calcium and dietary protein intake are known to be important in the development of osteoporosis. This proposal will test the hypothesis that human bone cells express a protein which senses calcium and amino acids, the calcium-sensing receptor, and thereby respond to nuritional signals arising from the presence of calcium ions and amino acids in plasma. Furthermore, we propose that by promoting osteoblast proliferation, maturation and survival, the calcium sensing receptor acts as the key molecular mechanism by which dietary calcium and protein promotes bone formation.These studies have potential to explain relationships between bpne resorptive activity, which raises local calcium concentrations, and bone formation activity and the coupling of bone forming and resorbing activity. These studies have the potential to explain the positive effects of calcium and protein intake on bone mass and may also shed light on the regulation of the coupling between osteoblastic and osteoclastic activityRead moreRead less
Investigating The Cellular Requirement For STIM1 Phosphorylation And Store-operated Calcium Entry Suppression During Mitosis: Roles In Development And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$344,900.00
Summary
Cells are constantly interacting with and modifying their surrounding environment. The intracellular calcium signal is one mechanism cells use to translate signals from the microenvironment into cellular responses. This proposal seeks to explore why a key calcium signalling pathway, known as store-operated calcium entry, is specifically silenced during cell division, and to determine how reversing this inhibition affects cell division during normal development and in cancer.
Receptor Signalling Through Intracellular Calcium Stores In Chromaffin Cells
Funder
National Health and Medical Research Council
Funding Amount
$461,000.00
Summary
The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modi ....The function of cells in the body is controlled by many hormones and neurotransmitters acting on the cell's surface. Hormones and transmitters mediate their effects by producing chemical signals within the cell that regulate its activities. One key cell signalling chemical is calcium, especially in nerve cells which have developed sophisticated mechanisms for using calcium to control their function. Recently, new levels of complexity have been discovered, both in how cell calcium levels are modified by hormones and transmitters and in how these complex calcium signals are used by cells to control their function. This project will investigate how hormones and transmitters can produce different types of calcium signals in nerve cells, and how these signals affect different aspects of the nerve cell's function. In particular, it will establish how two different types of specialised calcium stores within nerve cells are used by different classes of hormone and transmitter, and the distinct cellular functions these two calcium stores can regulate. The results will provide fundamental new information on how nerve cells control their activity and may help identify potential new targets for drugs.Read moreRead less
Active Transport Of Calcium Across Dental Enamel Cells - Testing A New Paradigm
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
Dental enamel defects and tooth loss affect over half our population, resulting in substantial suffering and economic costs. It is likely that many enamel defects could be prevented, and replacement teeth made more lifelike, if more was known about the cells responsible for producing enamel. A particular problem is our lack of understanding about how enamel-forming cells avoid overdosing on calcium, which can lead to cellular toxicity. The overall aim of this research is to use the latest cell b ....Dental enamel defects and tooth loss affect over half our population, resulting in substantial suffering and economic costs. It is likely that many enamel defects could be prevented, and replacement teeth made more lifelike, if more was known about the cells responsible for producing enamel. A particular problem is our lack of understanding about how enamel-forming cells avoid overdosing on calcium, which can lead to cellular toxicity. The overall aim of this research is to use the latest cell biology and biochemical techniques to elucidate the mechanisms of calcium handling in enamel cells, with developing teeth from rat as the experimental model. Our focus is on calcium transport mechanisms, a field where past theories were overturned by our recent findings with gene-knockout animals. We will test a new theory that has arisen from our investigations, using drugs and gene-silencing techniques to interfere with the cellular machinery now thought to be crucial for transporting calcium. By providing strong physiological evidence for this new mechanism, our expected results will define specific proteins that might be targeted by drugs and nutrition, and provide important information about how dietary fluoride and caffeine affect enamel quality. These findings would change thinking about how enamel defects can be prevented and provide a solid foundation to the exciting new field of dental bioengineering, whose goal is to coax stem cells to make natural replacement teeth.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.