Caspase 8 Apoptotic Signalling Induced By The Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$603,126.00
Summary
The death of cells of our body can be an active and purposeful process. Programmed death occurs in response to infection or as a defence against cancerous changes. If a virally infected cell can die prior to replication of the virus, this will control the infection. We have investigated cell death in response to DNA found in the cytoplasm of cells, which can be an indication of infection. The novel cell death pathway we are characterising is relevant to defence against infection and tumours.
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
A New Function For An Old Enzyme: Src Protein Kinase Directs Excitotoxic Neuronal Death In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$513,975.00
Summary
In our previous investigation of how brain cells die in patients suffering from stroke, we found that stroke causes aberrant activation of an enzyme called Src in the affected brain cells. Furthermore, this aberrantly activated Src directs the brain cells to undergo cell death. Our proposal, which aims to decipher this neurotoxic mechanism of the aberrantly activated Src will benefit development of new therapeutic strategies to reduce brain damage in stroke patients.
Defining The Molecular Regulators Of Apoptotic Cell Disassembly And Their Role In Cell Clearance And Lupus-like Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$773,848.00
Summary
In humans, billions of cells will die daily as part of normal turnover in various organs. It is vital that dying cells are rapidly removed as their accumulation has been linked to autoimmunity and inflammation. To aid efficient removal of dead cells, dying cells can disassemble into smaller fragments for neighbouring cells to engulf. We aim to understand the machinery that controls how dying cells can disassemble into smaller pieces and their function in cell clearance and autoimmunity.
Neuro-Cardiac Genetic Basis Of Sudden Unexpected Death In Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$575,288.00
Summary
Sudden unexpected death in epilepsy (SUDEP) is the most common epilepsy-related cause of death and accounts for up to 18% of all deaths. SUDEP is characterised by a sudden and unexpected death, where the post-mortem is normal. The underlying cause of SUDEP remains unknown. This study seeks to investigate the genetic causes of SUDEP. Identification of the causes of SUDEP has important implications for our understanding of disease mechanisms, and in translating these discoveries into both diagnost ....Sudden unexpected death in epilepsy (SUDEP) is the most common epilepsy-related cause of death and accounts for up to 18% of all deaths. SUDEP is characterised by a sudden and unexpected death, where the post-mortem is normal. The underlying cause of SUDEP remains unknown. This study seeks to investigate the genetic causes of SUDEP. Identification of the causes of SUDEP has important implications for our understanding of disease mechanisms, and in translating these discoveries into both diagnostic and prevention strategies in at-risk families.Read moreRead less
Investigating The Contribution Of Distinct Mitochondrial Cell Death Pathways To Platelet Survival And Function
Funder
National Health and Medical Research Council
Funding Amount
$635,247.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to im ....Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to improve current protocols for storing plateletsRead moreRead less
ARC, A Newly Identified Regulator Of Chondrocyte Differentiation And Death, Is A Novel Therapeutic Target For OA
Funder
National Health and Medical Research Council
Funding Amount
$763,983.00
Summary
We have identified a critical regulator of the survival and normal metabolism of the cells in articular cartilage. Loss of this molecule is an early event in joint injury that leads to osteoarthritis (OA). The current proposal will determine the mechanisms whereby this protein functions to protect cartilage breakdown in OA, how its levels in chondrocytes are regulated in both healthy and diseased conditions, and at what stages of disease increasing its expression protects against OA progression.
Sudden cardiac death (SCD) is a tragic consequence of a number of heart diseases. The death is often unexpected and has major implications for the family and community. This 3-year study seeks to evaluate clinical, genetic, and long-term outcomes in Australian families where SCD has occurred in a young relative (aged 1-35 years). This study will improve clinical and genetic evaluation of families, resulting in targeted management strategies, with the ultimate goal to prevent SCD.
Deciphering The Function Of Caspase-2 In DNA Damage Response And Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$808,007.00
Summary
Aberrant cell death and DNA damage response (DDR) are hallmarks of tumourigenesis. Recently we have discovered that an enzyme, caspase-2, previously implicated in cell death execution, also works in DDR and acts as a tumour suppressor. We now wish to validate these finding in preclinical models of cancer and understand precisely how caspase-2 safeguards against cancer development. These studies will help better understand tumourigenesis and may lead to the discovery of new drug targets.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.