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.
Unconventional Mechanisms For Activating The NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$747,031.00
Summary
Many inflammatory driven diseases such as arthritis, atherosclerosis and septic shock are also associated with cell death. This project will identify, at the molecular level, how cell death signalling specifically acts to trigger pathological inflammation. As such, it will identify novel targets for the development of next generation anti-inflammatory drugs.
Host Cell Death Signaling And Susceptibility To Bacterial Gut Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,321.00
Summary
Bacterial infections are a major cause of infectious disease worldwide. Here we aim to characterise immune responses that help fight infection by E. coli and Salmonella. These bacteria have evolved ways to shut down many of our immune responses during infection, allowing them to survive and cause disease. This work will help understand the complex relationship between gut bacteria and our immune system and provide solutions for controlling infection and treating immune disorders of the gut.
Aurora Kinase: Molecular, Cellular And Functional Studies Deciphering Its Role In Stroke Injury
Funder
National Health and Medical Research Council
Funding Amount
$580,993.00
Summary
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating an enzyme called aurora kinase A (AURKA). We aim at unravelling (i) how AURKA is activated by oxygen deprivation, (ii) where the activated AURKA is localised in cells, and (iii) how the activated AURKA induces nerve cell death.The study will benefit development of therapeutic strategies to protect against brain damage in stroke since this is novel and different target for drug targeting.
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.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.
What Is The Molecular Mechanism Underlying Cell Death By Necroptosis?
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Recently, we and others have demonstrated that part of the MLKL protein is able to kill cells. This process is known to cause a number of pathologies, including those arising from stroke. Blocking this type of cell death has thus emerged as an attractive therapeutic strategy. However, precisely how MLKL kills cells remains unclear and controversial. In this project, we will resolve these controversies with the goal of an increased fundamental understanding to aid drug discovery.
Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
Targeting Caspase 8 In T-Cell Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,215,780.00
Summary
Chronic infectious diseases such as HIV, hepatitis B and tuberculosis impose a massive global health burden and new treatments are desperately needed. This proposal investigates a new approach to improve immune responses and clear chronic infections. Our multidisciplinary team will define the molecular and cellular biology underlying this approach and translate our findings by re-purposing a drug already approved for other indications in humans.
Conologues: Ultra-fast-acting Therapeutic Insulins Based On Cone Snail Venom Insulin Principles
Funder
National Health and Medical Research Council
Funding Amount
$1,082,866.00
Summary
The increasing prevalence of Type 1 and Type 2 diabetes demands better treatments. Our Project is based on a fascinating discovery by our international team of CIs of a new type of insulin within marine organisms that could form the basis of a novel diabetes therapeutic. Within our Project we will exploit this discovery to develop a new class of ultra-rapid-acting therapeutic insulins.