Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.
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.
The Opposing Genetic Networks Underlying Plasticity Of Humoral Responses
Funder
National Health and Medical Research Council
Funding Amount
$667,783.00
Summary
The immune system makes antibody to clear bacterial and viral pathogens. Specialised types of antibody are needed for different pathogens. This project will study genetic changes that determine the specificity of an antibody response. Regulation of these genes may prohibit production of antibodies and inflammatory mediators that attack the body rather than foreign pathogens. Understanding these processes will identify points of therapeutic intervention for patients with immune disorders.
Rotavirus is the main cause of severe diarrhoea in children worldwide. In this project, we aim to understand the nature of the first-line immune response to rotavirus in the gut, and elucidate how RV counteracts this response to promote infection. These studies will increase our understanding of how rotavirus causes disease, and facilitate the choice of rotavirus targets for drug development and improved vaccines.
Targeting The Complement Cascade: A Novel Therapeutic Strategy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$546,496.00
Summary
The incidence of melanoma is increasing world-wide, and Queensland has the highest rate of melanoma in the world. Despite advances in treatment, the 3-year survival rate for metastatic melanoma remains extremely low. This project builds on our recent research demonstrating a role for a key component of the innate immune system (complement C3a) in melanoma growth. Specifically we seek to investigate the potential of C3a as a therapeutic target for metastatic melanoma.
Complement Inhibitors For Treatment Of Chronic Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$623,606.00
Summary
We aim to provide new therapeutic approaches to gum disease, which not only causes tooth loss, but also contributes to other diseases, such as cardiovascular disease and diabetes. We will find new methods to inhibit a system in our own bodies that contributes to inflammation and gum disease and test the effects of these methods of inhibition in disease models. In this way, we hope to lessen the burden of gum disease on the Australian population.
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?
Therapeutic Targeting Of Complement C5a Receptors In HuntingtonÍs Disease
Funder
National Health and Medical Research Council
Funding Amount
$468,312.00
Summary
HuntingtonÍs disease is a genetic neurodegenerative condition leading to progressive cognitive and motor deficits and eventual death. This research aims to explore the role of immune and inflammatory pathways in the progression of disease in patients suffering HuntingtonÍs disease, as well as in an animal model of this condition. By exploring these immune and inflammatory pathways, we aim to identify novel therapeutic targets to treat HuntingtonÍs disease.