Inflammasome Sensors And Immune Protection Against Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$750,110.00
Summary
Intestinal cancer is a leading cause of death in Australia and worldwide. Defects in the immune system can lead to the development of intestinal cancer. In this project, we will investigate the critical role of an immune sensor in inhibiting the development of intestinal cancer. This project will provide new insights into the interplay between the immune system and cancer biology and will potentially inform the development of new immunotherapies.
Inflammasome Function In Gastrointestinal Immunity And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$421,116.00
Summary
The immune system in the gut provides a vital defence against microbes. If these defences are ineffective we become infected leading to gastroenteritis, a major cause of death in the third world and hospitalisation in developed countries. Conversely, excessive or inappropriate activation of these defences can cause inflammatory disease. This project will investigate microbial detection in the gut, and aims to discover new, more effective ways to treat gastrointestinal infection and inflammation.
Metabolic Homeostasis: A Potentially Novel Regulatory Pathway Involving Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Altered metabolic regulation contributes to ageing and the development of obesity, type II diabetes and cancer. Recently we discovered that an enzyme, caspase-2, is involved in metabolism, oxidative stress and ageing. We now wish to identify how caspase-2 regulates key metabolic pathways during ageing and nutritional stress. These studies will help to better understand metabolic control and may lead to the discovery of new drug targets to promote healthy ageing and prevent disease.
In a human body, about a million cells are born every second, and a million die by activating a physiological cell death mechanism. If cell death fails to occur, cells accumulate and can develop into cancers. Determining the mechanism and regulation of physiological cell death will provide novel approaches to treat cancers and auto-immune diseases, both of which are characterised by failure of certain cells to die.
Regulation Of Autoimmunity By Non-apoptotic Caspases
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Excessive cell death can lead to chronic inflammation and autoimmunity. Cells can die by different mechanisms including necroptosis which causes inflammation, and apoptosis which does not. Recent studies show that caspases, a component of the apoptosis pathway which accelerate cell death, also prevent immune activation by dying cells. I will investigate whether caspases contribute to autoimmune disease and whether caspases can dampen the inflammation that occurs during necroptotic cell death.
Using Mouse Models To Decipher The Function Of Caspase-2 In Limiting Aneuploidy Tolerance And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$871,162.00
Summary
Aneuploidy or abnormal chromosome number is a feature of cancer cells. The extent of aneuploidy is often predictive of prognosis and the effectiveness of cancer treatment. We discovered that a tumour suppressing protein, caspase-2, is important for deleting aneuploid cells that may otherwise become cancerous. In this project we will use cancer models to decipher how caspase-2 safeguards against aneuploidy and cancer to better understand how cancer cells can survive and be targeted for treatment.
The pathology of many acute and chronic diseases associated with the inappropriate activation of genetically encoded programmed cell death pathways, such as sepsis, stroke, diabetes and neurodegeneration, is linked to detrimental inflammation. This project will accurately define at the molecular level how programmed cell death triggers inflammatory responses, and use this knowledge to test novel and next-generation therapeutic strategies in inflammatory-driven diseases.
Understanding The Role Of Caspase-2 In Cellular Stress Response And Ageing
Funder
National Health and Medical Research Council
Funding Amount
$918,517.00
Summary
This project builds upon our recent findings showing that a protein, called caspase-2, is involved in protecting against oxidative damage and ageing in a mouse model. We propose to carry out further studies to fully understand how caspase-2 regulates cell’s response to oxidative stress. Such studies will be critical in assessing if caspase-2 or its substrates are useful targets for drugs to treat diseases that may arise due to cell’s inability to properly respond to oxidative damage.