Viral Targeting Of STAT Proteins: Roles In Disease
Funder
National Health and Medical Research Council
Funding Amount
$536,985.00
Summary
The capacity of viruses to evade the host immune response is critical to the development of disease. We recently showed that interaction of specific viral proteins with host immune proteins called STATs is vital to lethal disease caused by lyssaviruses. In this project, we aim to define in detail the functions of these interactions in viral modification of host biology and evasion of the immune response, and to use this information to develop new vaccines against highly pathogenic human viruses.
Understanding Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,043,216.00
Summary
This project opens a new line of enquiry into the cellular signalling mechanisms involved in the progression of AD and establishes whether targeting the involvement of type-1 IFN signalling influences the evolution of AD. New and novel approaches are clearly required to treat AD. Importantly, we believe that neuroinflammation is common to all causes of dementia and targeting the neuroinflammatory pathways has much wider implications than targeting the primary causative pathway.
Controlling Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide, with 269,000 Australians currently diagnosed with AD and is expected to soar to about 981,000 by 2050. AD accounts for greater than 60% of all cases of dementia. This grant investigates the role that neuroinflammation plays in the progression and exacerbation of AD and will identify new therapeutic strategies to combat this insidious disease.
Interleukin 38: Uncoupling Innate Inflammation From Interferons In Lupus
Funder
National Health and Medical Research Council
Funding Amount
$1,048,669.00
Summary
Systemic lupus erythematosus (SLE) is an incurable autoimmune disease that affects 5 million patients worldwide, mostly young women. Grave multi-organ inflammation and substantial loss of life expectancy render SLE a critical unmet medical need. We found that the immune system protein interleukin 38 disables several signalling pathways essential for SLE progress. We will explore regulation and function of this protein in cells from healthy people and SLE patients and in models of the disease.
Anti-viral Immunity In Asthma: A Detailed Assessment Of TLR7 Function And The Regulation Of Interferon ?/? Synthesis.
Funder
National Health and Medical Research Council
Funding Amount
$517,156.00
Summary
Many people with asthma are unusually vulnerable to viral infections. This study will carefully examine different components of immune function in people with asthma, including the receptors that respond to viral nucleic acids and the reasons why people with asthma do not produce normal quantities of anti-viral interferons. This research may lead to novel methods for prevention and treatment of virus infections in people with asthma.
Investigating Type I Interferon-mediated Immune-suppression During Plasmodium Infection
Funder
National Health and Medical Research Council
Funding Amount
$561,617.00
Summary
Some infections tend to afflict us only once in our lifetimes, for example chickenpox. This is because our bodies develop immunity to these infections relatively easily. The same is not true for malaria. It is thought that our immune systems are somehow suppressed during this disease. This project aims to understand how the immune system is suppressed during malaria infection, in order that we can block this process, and help our bodies fight this disease more effectively.
Testing The Prion Hypothesis In Parkinson’s Disease Using A Novel In Vivo Model Of Α-synuclein Transmission
Funder
National Health and Medical Research Council
Funding Amount
$622,555.00
Summary
Parkinson’s Disease (PD) is a debilitating neurological disease with no cure. Recently it has been discovered that the disease can spread through the brain. We have developed the worlds first animal model to study exactly how the disease propagates inside of neurons during this spread. We will use the model to answer key questions about this critical stage of disease spread, knowledge that is essential for the development of successful therapies to prevent disease progression.
Loss Of Cytostatic Regulation By TGF-beta During EGFR-driven Tumor Development
Funder
National Health and Medical Research Council
Funding Amount
$605,031.00
Summary
Growth factor and cytokine signalling networks control many aspects of cell behaviour such as proliferation, survival, migration, invasive capabilities, transformation and differentiation. In normal cells, these complex signalling pathways are tightly regulated. Alterations of these signals are often found to cause, directly or indirectly, tumour formation. Transforming Growth Factor-b (TGF-b) and Epidermal Growth Factor (EGF) signalling pathways are both independently implicated as key regulato ....Growth factor and cytokine signalling networks control many aspects of cell behaviour such as proliferation, survival, migration, invasive capabilities, transformation and differentiation. In normal cells, these complex signalling pathways are tightly regulated. Alterations of these signals are often found to cause, directly or indirectly, tumour formation. Transforming Growth Factor-b (TGF-b) and Epidermal Growth Factor (EGF) signalling pathways are both independently implicated as key regulators in tumour formation and as such they are potential therapeutic targets. However, while both pathways have been studied extensively, little is known about the cross-talk between the TGF-b and EGF pathways. This project will establish the generality of a new tumor signaling axis, namely EGFR-Stat3-Smad7-TGF-b in EGFR-overexpressing tumors. Practically, it will provide guidelines for the development of new approaches for treating effectively the EGFR-driven tumors.Read moreRead less
21,000 Australians receive kidney replacement therapy and many more die of kidney failure as a result of kidney fibrosis. TGF-?, a growth factor causing kidney fibrosis, is also anti-inflammatory and promotes healing. We aim to prove that targeting downstream messengers (Foxo/?-catenin) of TGF-? will prevent fibrosis while promoting TGF-?’s anti-inflammatory and healing actions. A successful outcome will lead to a novel cure for preventing kidney failure and failure of other organs.
The Role Of TGFB1 In The Pathophysiology Of Late Stage Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$612,961.00
Summary
Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their ....Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their disorder progresses.Read moreRead less