Determining The Role Of DOCK8 In CD4+ T And B Cell Differentiation And Its Implications On Autosomal Recessive Hyper IgE Syndrome (AR-HIES)
Funder
National Health and Medical Research Council
Funding Amount
$512,600.00
Summary
Autosomal recessive hyper IgE (AR-HIES) syndrome due to mutations in DOCK8 is a rare primary immunodeficiency whereby patients present with susceptibility to severe and recurrent viral infections as well as an increased risk of developing cancer, severe food and environmental allergies, and atopic disease characterised by hyper IgE and extreme eosinophilia. This grant will investigate how abnormal DOCK8 function in CD4+ T cells and B cells contributes to disease pathogenesis in AR-HIES patients.
Mechanisms And Targets Of Antibody-complement Interactions That Neutralize Malaria
Funder
National Health and Medical Research Council
Funding Amount
$647,977.00
Summary
Our project aims to identify immune mechanisms that neutralize malaria from the moment of inoculation by a mosquito, before infection can become established to prevent the development of malaria disease. Furthermore, we will discover specific targets of protective immune responses. We expect this project will provide major new advances in our knowledge of human immunity to P. falciparum malaria, one of the world’s most significant causes of mortality and morbidity, and we will use this knowledge
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.
Understanding The Role Of MAIT Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,593.00
Summary
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells protect us from bacteria and yeast at mucosal sites where the body's immune defences are most easily breached, e.g. gut, oral cavity, airways & reproductive tract. This study investigates the role of MAIT cells in health and in diseases like inflammatory bowel disease, peptic ulceration, periodontitis and tuberculosis. Controlling MAIT cells could help in treating these conditions.
Therapeutic Vaccine Against Non-Hodgkin's Lymphoma Targeting The Immune Adjuvant Properties Of Natural Killer T Cells.
Funder
National Health and Medical Research Council
Funding Amount
$451,606.00
Summary
Patients with lymphoma cancers initially respond well to treatment, but later relapse with disease. The immune system can be effective at controlling cancer. A potential treatment option is to boost the natural immune response against cancer. This study investigates a vaccine that activates a certain immune cell, NKT cells, to fight lymphomas by delivering an NKT cell-activating molecule. Outcomes will allow assessment of combining an NKT-based vaccine with established treatments for lymphoma.
A vaccine for hepatitis C virus (HCV) is not yet available. Immune responses that are able to protect against infection are possible, making the production of a vaccine a realistic goal. We have produced a unique HCV vaccine and are now poised to test our vaccine in novel humanised animal models. Our research will allow us to determine the immune responses responsible for providing protection against HCV. Our data will be highly significant for future HCV vaccine studies in humans.
Using Influenza Vaccination To Understand And Improve Anti-viral Immunity In COPD
Funder
National Health and Medical Research Council
Funding Amount
$1,316,597.00
Summary
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. Lung infections often make those afflicted by COPD very unwell. We have recently shown that influenza vaccination induces a poor antibody response in many COPD patients. This study will examine why this is the case, and what can be done to restore normal immune function. In the final year of the Project, we will assess whether doubling the dose of influenza vaccination is helpful.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that result in the generation of mucosal memory T cells that are resistant to virus infection.