How Does Iron Accumulation Affect Parkinson’s Disease And What Controls It?
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
Currently there is no cure for Parkinson's disease, and although we have a number of treatments to manage the disease there is an urgent need for a further understanding of the disease process. This proposal will investigate the critical role that iron plays in the cause of neuronal cell death that results in Parkinson's disease, and will investigate methods for regulating metal levels in the brain.
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.
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.
Structural Investigations Of The Bcl-2 Family Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$612,652.00
Summary
Programmed Cell Death is a process by which dangerous cells are removed from the body. Sometimes it goes wrong and causes disease, e.g. cancer cells stay alive when they should die. This project will study a group of proteins that regulate cell death, the Bcl-2 family of proteins, in order to understand the mechanism by which they control the balance of cell life and death. The findings will inform the development of new drugs aimed at regulating cell death in a variety of disease states.
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
Contribution Of Complement C5a To Neuronal Cell Death During Ischemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$455,263.00
Summary
Ischemic stroke remains the second leading cause of death in Australia. This project aims to understand the role the innate immune system plays in neuronal cell death following ischemic stroke. We will use cellular and animal models of ischemic stroke, as well as examine patients affected by stroke, to explore and inhibit potential damaging immune factors generated by stroke tissue. By exploring these immune pathways, we aim to identify novel therapeutic targets to treat ischemic stroke.
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.
Effects Of Intestinal Inflammation On Functioning Of Enteric Neurons: From Animal Models To Humans
Funder
National Health and Medical Research Council
Funding Amount
$345,206.00
Summary
Crohn’s disease and ulcerative colitis, two debilitating conditions known as Inflammatory Bowel Disease (IBD), affect more than 61,000 Australians. There is no cure for IBD. All gut functions are controlled by enteric neurons in the gut wall. Inflammation causes damage and death of these neurons leading to gut dysfunctions. This is the first study defining the classes of human enteric neurons affected by inflammation. This study will test several potential new targets for the treatment of IBD.
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.
Neurogenesis In The Amygdala And Hippocampus: A Role In Learnt Fear?
Funder
National Health and Medical Research Council
Funding Amount
$780,396.00
Summary
It has long been thought that neurons are only born once and then slowly die. Learning and memory formation is thought to occur by changes in the strength of connections between living neurons. However, the hippocampus is now known to produce new neurons throughout life. We have found that neurons are also born in the adult amygdala. In this project we will study how neurogenesis affects learning and memory formation that involve the hippocampus and amygdala.