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
Altered Intracellular Signalling In Response To Hyperglycaemia Reflects An Inherent Predisposition To Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$164,061.00
Summary
Diabetic nephropathy affects 30-50% of patients with diabetes mellitus. The reasons as to why only a proportion of patients develop this devastating complication is not clear. Poor control of blood sugar levels has been well characterised as being of aetiological importance in its genesis, but is clearly not the sole factor responsible. Genetic factors appear to predispose individuals to developing diabetic nephropathy, with a significantly higher number of affected patients having a family hist ....Diabetic nephropathy affects 30-50% of patients with diabetes mellitus. The reasons as to why only a proportion of patients develop this devastating complication is not clear. Poor control of blood sugar levels has been well characterised as being of aetiological importance in its genesis, but is clearly not the sole factor responsible. Genetic factors appear to predispose individuals to developing diabetic nephropathy, with a significantly higher number of affected patients having a family history of hypertension and vascular disease. Our own preliminary studies using cells from human kidneys have demonstrated that there are clearly 2 responses observed with respect to alterations in intracellular signalling after exposure to high glucose concentrations and hormones known to be of importance in the development of diabetic nephropathy (such as angiotensin II and insulin-like growth factor-1). These responses appear to be specific to the patient from which the kidney tissue is derived. Thus the aim of the present study is to determine prospectively, whether the groups differ with regards their intracellular signalling and subsequent development of tubulointerstitial pathology in an in vitro model of diabetes mellitus.Read moreRead less
Signalling To Telomeres: Mechanisms Of Action Of TGFb
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is contro ....Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is controlled by another protein called c-myc. This work will determine how telomerase is controlled by a balance between TGFb and c-myc in order to find ways to control telomerase and therefore cancer. We will use a combination of sophisticated techniques of cell molecular biology and biochemistry to pinpoint and target different molecules implicated in the actions of TGFb. This study will serve as an important baseline for more applied research in controlling ageing and cancer from development.Read moreRead less
The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.
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.
Regulation Of PtdIns(3,4)P2 Signalling By Inositol Polyphosphate 4-phosphatase-1
Funder
National Health and Medical Research Council
Funding Amount
$557,939.00
Summary
Normally cells only divide when they receive a stimulus such as from a hormone or growth factor. One of the signaling pathways which responds to growth factor stimulation is the PI3-kinase pathway. This pathway has been implicated in many different human cancers which occur when cells divide uncontrollably and invade into the surrounding tissues. We have idenitified a novel enzyme called the inositol polyphosphate 4-phosphatase that appears to regulate cell proliferation and differentiation.