The Molecular Mechanism Of Sphingosine Kinase Activation
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Many cell processes like growth, death and differentiation are controlled by hormones and other molecules that interact with receptors on the outside of the cell. When this type of molecule binds to a receptor, it often triggers the production of signaling molecules inside the cell that initiate a change in the cells behaviour. The lipid molecule, sphingosine phosphate has been identified as such a signaling molecule that appears to be involved in the regulation of a diverse array of important m ....Many cell processes like growth, death and differentiation are controlled by hormones and other molecules that interact with receptors on the outside of the cell. When this type of molecule binds to a receptor, it often triggers the production of signaling molecules inside the cell that initiate a change in the cells behaviour. The lipid molecule, sphingosine phosphate has been identified as such a signaling molecule that appears to be involved in the regulation of a diverse array of important mammalian cellular processes. Recent studies have found that sphingosine phosphate is involved in the inflammation of cells, and if its production can be blocked, inflammation is not seen. Therefore, this provides a potential target for therapeutic intervention in the inflammation process. However, the manner by which cells regulate sphingosine phosphate levels is not well known. It is known that sphingosine phosphate is produced by the enzyme sphingosine kinase, and strong evidence suggests that changes in this enzyme's activity in the cell regulate sphingosine phosphate levels. However, how the cell changes the levels of sphingosine kinase activity is completely unknown. This study will investigate this problem with the view that understanding this process will allow the development of new drugs to block increases in sphingosine kinase activity, preventing increases in sphingosine phosphate levels, and it turn, preventing cellular inflammation.Read moreRead less
Mechanisms Of Gender Differences In Genetic Aortopathy
Funder
National Health and Medical Research Council
Funding Amount
$122,686.00
Summary
This project will investigate the molecular mechanisms that underly the gender differences in phenotypic expression in young adults with genetic aortopathy.
Centrosome Overduplication Contributes To Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$495,010.00
Summary
Cancer can be simplistically thought of as a disease of cell growth and division. In order to improve current treatment regimes and identify new ones, the underlying mechanisms controlling cell proliferation need to be fully understood. By defining these regulatory mechanisms, targets for current chemotherapeutic agents can be further characterised and new ones identified. This will lead to the targeted developments of new classes of drugs which can be used in the fight against cancer.
Regulation And Function Of The Protein Tyrosine Phosphatase TCPTP In Mitosis
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
The cell cycle is a universal process by which cells reproduce and it underlies the growth and development of all living organisms. The most important events of the cell cycle concern the replication of chromosomal DNA during S phase and the separation of replicated DNA into progeny cells at mitosis. Mitosis is morphologically the most dynamic phase of the cell cycle and involves the precise coordination of many processes that are governed by reversible protein phosphorylation. Protein phosphata ....The cell cycle is a universal process by which cells reproduce and it underlies the growth and development of all living organisms. The most important events of the cell cycle concern the replication of chromosomal DNA during S phase and the separation of replicated DNA into progeny cells at mitosis. Mitosis is morphologically the most dynamic phase of the cell cycle and involves the precise coordination of many processes that are governed by reversible protein phosphorylation. Protein phosphatases play an important role in reversible protein phosphorylation and they are essential for mitosis. This grant proposal is focused on understanding the regulation and function of protein phosphatases in mitosis. Our studies will provide novel insight into processes mediating mitosis and may lead to the development of alternative strategies for treating cancer.Read moreRead less
Nuclear Functions Of Dengue NS5 Protein: Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$736,953.00
Summary
Our work indicates that the NS5 protein from Dengue virus (DV) has distinct sequences that enable it to traffic into and out of the host cell nucleus to exert pathogenic effects on transcription and thereby impair the host cell anti-viral and immune responses. We aim to characterise these properties in detail, and demonstrate their importance to DV pathogenicity using a novel animal model of the disease.
Regulation Of Endothelin Converting Enzyme Subcellular Distribution And Vascular Endothelin Production.
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not ....Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not only help us better understand the mechanism of endothelin production but it may also offer an insight into future therapeutic startegies to prevent the formation of endothelin, thus preventing vasoconstriction.Read moreRead less
Role Of Sphingosine Kinase 1 In PP2A-associated Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$522,994.00
Summary
Defects in protein phosphatase 2A (PP2A) are widely associated with the development of solid tumors and leukemia. The precise mechanisms whereby defects in PP2A lead to cancer, however, remain undefined. We have recently identified that the oncogenic protein sphingosine kinase 1 (SK1) as a target of PP2A. In this study we will examine the role of SK1 in PP2A-associated cancers. Successful outcomes in these studies will establish SK1 as a target for therapeutic intervention in these cancers.
Mechanisms Of Regulation And Biological Roles Of Sphingosine Kinase 2
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
We have identified that a protein called sphingosine kinase 2 (SK2) is a potential target for anti-cancer therapies. Our preliminary studies indicate that phosphorylation of SK2 controls its function. In this proposal we will define how phosphorylation alters SK2 function so that potential therapies may be developed to target this process.