A Novel Cytokine-receptor Survival Axis In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$424,731.00
Summary
Cancer cells grow and survive in an unrestrained manner. Current therapies target cancer growth, however they permit the long-term survival of some cancer cells and increase the possibility of drug resistance and disease relapse. We have identified a new molecular switch that is constitutively activated (unregulated) in leukemia. Targeting specific components of this unregulated cell survival may provide new and improved approaches for the development of therapeutics in the treatment of leukemia
Characterisation Of A New Family Of Proteins Involved In Cell Signalling, RNA Metabolism And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of th ....We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of these RNA-binding proteins have been identified. We have shown that the novel protein discovered in our laboratory is perturbed in cancer and we are interested in characterising its putative role in cancer. The results established in our laboratory so far would indicate that generally, G3BP-2 is expressed in normal tissue and it expression changes in some cancers studied so far. Considering that G3BP-2 lies in a pathway known to be involved in cancer progression it is important to understand what effects the inappropriate expression of G3BP-2 may have on cancer progression and survival. This project is designed to characterise what signals the cell uses to control these proteins and in turn which genes these may effect. In this way we may be able to determine how external signals may effect tumour progression and on what genes this influence is expressed. It would be hoped that this project would increase our understanding of cancer and potentially lead to new diagnostic reagents and therapies in the treatment of cancer.Read moreRead less
Role Of Conformational Change In Activation Of The Growth Hormone Receptor
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that ....Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that the primary event in signalling is the ability of the hormone to bring two receptors together (receptor dimerization). However, it may be that the receptor already is dimerized, and the role of the hormone is to induce a specific change in shape of the receptor, which transfers the signal of hormone binding into the cell to initiate signalling to the genome. We have good evidence that a specific shape change is required for activation of an important signalling pathway by growth hormone, and the closely structurally related receptor for erythropoietin is already dimerized before hormone binds. We want to find out exactly how the shape change acts, and whether the receptor is predimerized. This information is vital for designing small orally active mimics of growth hormone which could be of great value as an anabolic supplement for the frail elderly.Read moreRead less
Function Of The S100A1 Ca2+-binding Protein Under Physiological And Pathological Conditions
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
The S100A1 protein is one of the most abundant proteins in human heart muscle cells. It binds calcium ions and may play a role in the regulation of heart function. S100A1 levels are reduced in human heart failure, but it is unclear whether this reduction contributes to worsening of the disease. To study this, we have generated a genetically modified mouse strain that cannot make the S100A1 protein. We will use these mice to study how important the protein is for heart function under normal condi ....The S100A1 protein is one of the most abundant proteins in human heart muscle cells. It binds calcium ions and may play a role in the regulation of heart function. S100A1 levels are reduced in human heart failure, but it is unclear whether this reduction contributes to worsening of the disease. To study this, we have generated a genetically modified mouse strain that cannot make the S100A1 protein. We will use these mice to study how important the protein is for heart function under normal conditions, and how it contributes to the development of heart failure. Preliminary data indicate that adult mice with reduced S100A1 protein levels develop a form of heart disease that significantly reduces the efficiency of the pump function of the heart.Read moreRead less
Structural Studies On Cell Signalling Via The LIF Receptor And Gp130
Funder
National Health and Medical Research Council
Funding Amount
$453,943.00
Summary
The cytokines play important roles in the immune system during blood cell development and inflammation, and in nerve growth, bone remodeling, reproduction and heart development. Cell responses are initiated by a cytokine bringing together on the cell surface a receptor complex made up of multiple molecules. This project will investigate the atomic structure of the cell surface macromolecular complex, and hence the underlying mechanism by which cytokine signals are initiated.