The majority of stroke results from focal brain infarction, followed by substantial secondary excitotoxic damage in the surrounding areas. Tau has been shown to contribute to excitotoxicity and neurodegeneration in mouse models of Alzheimer’s disease (AD). Preliminary data show that tau reduction also protects against excitotoxic damage after experimental stroke. We aim to dissect the molecular mechanisms of stroke using a tau-deficient mouse model.
Novel Role Of Innate Immune DNA Sensors In Promoting Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$774,025.00
Summary
Stomach cancer is the third most lethal cancer worldwide, and is strongly associated with inflammation (gastritis) caused by Helicobacter pylori bacterial infection. However it remains unknown how Helicobacter triggers gastritis and stomach cancer in people. Using a mouse model for gastritis-associated stomach cancer, our aim is to demonstrate the role of immune system proteins in the stomach which detect bacterial and host DNA to drive chronic inflammatory responses that lead to stomach cancer.
Individuals with stomach cancer, the second most lethal cancer world-wide, have a poor survival rate which is largely due to our poor understanding of the mechanisms which drive this deadly malignancy. Our aims are to identify how over-activation of a specific molecule of the immune system, called STAT3, in the mitochondria of cells promotes the growth of stomach tumours, and also examine whether blocking the actions of mitochondrial STAT3 can suppress the growth of gastric cancer cells.
Targeting PI3K-regulated Small Non-coding RNAs To Restore Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$610,204.00
Summary
Heart failure affects approximately 2.4% of the adult population and over 11% of people over 80 years old. The majority of existing therapies slow, rather than reverse heart failure progression. The primary goal of this study is to determine whether regulating novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
Slowing Progression Of Alzheimer’s Disease By Modulating The Kynurenine Pathway
Funder
National Health and Medical Research Council
Funding Amount
$578,460.00
Summary
Chronic inflammation in the brain in known to be a factor in the progression of Alzheimer's disease. We are exploring if blocking a particular enzyme in a biochemical pathway involved in inflammation, can improve symptoms, or slow progression, of the disease in animal models of AD. If results are as expected, our proposal has the potential to generate a new a therapy for AD.
Nedd4-2: A New Player In Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$671,995.00
Summary
Polycystic kidney disease (PKD) is a life threatening disorder affecting over 12 million people worldwide. This project is based on our discovery of a new gene that controls PKD. Using kidney specific gene knockout, biochemical and cellular approaches we will now address how this gene controls PKD. The results from this study will lead to better understanding of the underlying mechanisms that cause PKD, thus providing possible new targets for therapeutic interventions.
In Vivo Investigation Of Human PR3 Transgenic Mice: A Novel Animal Model To Understand The Role Of PR3 In Chronic Inflammation And Autoimmune Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$378,615.00
Summary
Granulomatosis with polyangiitis (GPA) is a form of vasculitis and is associated with antibodies directed against proteinase 3 (PR3). PR3 is expressed in neutrophils, monocytes and macrophages and has a number of well-characterized pro-inflammatory functions. The aim of this project is to understand the role of PR3 in inflammation and autoimmune vasculitis in vivo. This will be achieved using a transgenic mouse model expressing human PR3.
Investigating A New Regulator Of Cardiac Rhythm In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,022,704.00
Summary
Cardiac arrhythmias affect a high proportion of the population (2-5%) and can cause sudden death. Whilst the aetiology of arrhythmia can vary, there are clear genetic causes. Unfortunately, our knowledge of the genetic contributors is incomplete, hampering efforts to interpret genetic sequencing information. This project will undertake functional analyses of a novel arrhythmia gene and establish where, when and how it is required for correct cardiac rhythm.
Targeting A New Regulator Of Cardiac Pathology To Protect The Heart From Cardiac Dysfunction And Arrhythmia
Funder
National Health and Medical Research Council
Funding Amount
$717,857.00
Summary
Heart failure is associated with high mortality, and treatment of this condition represents a major unmet need. We recently reported that specific lipid species are elevated in hearts of mice with heart failure. The goal of this study is to comprehensively examine the therapeutic potential of targeting these lipid species with drugs.