Defective Repair Of Neuronal Activity-induced DNA Double Strand Breaks: A Novel Pathogenic Mechanism For Neurodegeneration In Ataxia-telangiectasia
Funder
National Health and Medical Research Council
Funding Amount
$570,821.00
Summary
The reason for degeneration of the hindbrain in patients with Ataxia-telangiectasia is unknown. Firing of neurons leads to breaks in the DNA that are normally repaired by ATM, the gene defective in Ataxia-telangiectasia, and failure to reset the system likely leads to abnormal gene expression and cell death. Here we use neuronal cell types derived from patient stem cells to elucidate how this novel disease mechanism may cause hindbrain degeneration and to test drugs that can overcome this.
The C-type Lectin Mincle Exemplifies A New Mode Of Sterile Inflammation In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$609,237.00
Summary
This project investigates two of the life-changing cardiovascular events that most commonly impact on Australians today; Heart attack and Stroke. These diseases often leave individuals debilitated with a long recovery period, and for many people the event is fatal. We have shown that blocking the action of an immune component, "Mincle", reduces the inflammation associated with stroke, and improves recovery. This project looks at what Mincle does in brain and heart muscle, and why blocking Mincle ....This project investigates two of the life-changing cardiovascular events that most commonly impact on Australians today; Heart attack and Stroke. These diseases often leave individuals debilitated with a long recovery period, and for many people the event is fatal. We have shown that blocking the action of an immune component, "Mincle", reduces the inflammation associated with stroke, and improves recovery. This project looks at what Mincle does in brain and heart muscle, and why blocking Mincle protects cells from loss of oxygen.Read moreRead less
Investigating The Apoptotic Function Of Bak And Bax
Funder
National Health and Medical Research Council
Funding Amount
$476,271.00
Summary
Proper regulation of how and when cells die is crucial for the development and maintenance of a healthy body and mind. We shall investigate the key proteins that are ultimately responsible for killing a cell with the long term view to identify ways to target these proteins for the treatment of conditions including neurodegenerative and cardiovascular diseases.
Characterization Of A Novel Regulator Of Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$592,235.00
Summary
PI3K is an enzyme required for new blood vessel formation during embryo development as well as in response to tumour formation. We have identified a novel enzyme that opposes PI3K signals and we hypothesise that it regulates new blood vessel formation in various physiological settings. We propose to investigate the role of this enzyme in blood vessels using mouse models in which this protein is reduced or absent.
Investigating Tumour Development And Metastasis Using A Novel Drosophila Cancer Model.
Funder
National Health and Medical Research Council
Funding Amount
$505,500.00
Summary
The majority of cancers are derived from epithelial cells. The primary cause of cancer related deaths is due to the ability of these epithelial cancer cells to migrate and invade other tissues within the body away from their primary tissue of origin (metastasise). This proposal seeks to understand the pathways that are important in regulating the processes of epithelial cell migration and invasion that are instrumental in promoting the metastatic spread of tumour cells. As controls usually opera ....The majority of cancers are derived from epithelial cells. The primary cause of cancer related deaths is due to the ability of these epithelial cancer cells to migrate and invade other tissues within the body away from their primary tissue of origin (metastasise). This proposal seeks to understand the pathways that are important in regulating the processes of epithelial cell migration and invasion that are instrumental in promoting the metastatic spread of tumour cells. As controls usually operate to induce cell death in any cell that attempts to break away and invade other tissues, this proposal also seeks to understand some of the pathways that are responsible for causing these cells to die. To carry out these investigations we have developed a novel Drosophila model of epithelial cancer development. We use this model because of the ease with which it is possible to carry out complex genetic analyses and so dissect the roles of the many different signalling pathways involved in these processes. The strength of the model is that it is dependent upon genetic alterations that are also implicated in the development and metastatic spread of many mammalian cancers, namely activating mutations in two genes, Ras and Notch. It is expected, therefore, to offer considerable insight into why these activated genes also cause the spread of cancer cells in humans.Read moreRead less
Analysis Of Rho GTPase Signalling Pathways In An Epithelial To Mesenchymal Transition During Development Of The Mesoderm
Funder
National Health and Medical Research Council
Funding Amount
$409,500.00
Summary
A critical step in the progression of cancers that are derived from epithelial tissues is a transition from an epithelial cell type to a migratory mesenchymal cell type that can spread to other parts of the body. This change in cell behaviour also occurs, apparently by a similar mechanism, during the development of some normal tissue types. Here we propose to use an animal model of this process, coupled with advanced molecular genetic and cell biological techniques, to investigate a newly discov ....A critical step in the progression of cancers that are derived from epithelial tissues is a transition from an epithelial cell type to a migratory mesenchymal cell type that can spread to other parts of the body. This change in cell behaviour also occurs, apparently by a similar mechanism, during the development of some normal tissue types. Here we propose to use an animal model of this process, coupled with advanced molecular genetic and cell biological techniques, to investigate a newly discovered cell signalling mechanism required for the transition of cells from an epithelial form to a mesenchymal form. Understanding the molecular steps in this new pathway and discovering new genes involved will provide tools for understanding and preventing the metastasis of cancer cells.Read moreRead less