Innate Immune Functions Of The Intracellular Antibody Receptor TRIM21
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
The immune system can fight viral infections with antibodies, which mark viruses outside of cells for elimination by immune cells. Antibody-coated viruses try to escape elimination by hiding inside cells. This project will determine how immune cells recognise the antibody-coated viruses ‘hiding’ within them, and the defence response they launch to eliminate viral infection. Such knowledge may allow us to develop better anti-viral drugs and vaccines to fight viral diseases like the common cold.
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
The Role Of A Novel Cytokine Of The Innate Immune Response In Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$344,407.00
Summary
Sexually transmitted infections represent a critical global health and socioeconomic problem with over 1 billion new cases per annum. I propose a world-first description of a new protein that has a protective role against herpes simplex virus (HSV) infection of female reproductive tract. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in HSV-2 infection.
PB1-F2 Is Critical To Influenza A Virus Pathogenicity Through Activation Of The Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$663,919.00
Summary
Fatal Influenza A virus infections are excessive inflammation. We identified the IAV protein PB1-F2 as critical in driving excessive inflammation via activating the host inflammasome complex. Our study evaluates PB1-F2-mediated inflammation contribution to inflammatory responses. Identifying PB1-F2 in emerging IAV strains is invaluable in aiding health policy makers to quickly assess fatal IAV pandemics. Our research will potentially identify treatment targets towards reducing this inflammation
Structural And Functional Investigation Of Killer-Cell Immunoglobulin-like Receptors
Funder
National Health and Medical Research Council
Funding Amount
$546,966.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used as a guide in the selection of bone marrow donors in the treatment of leukaemias as well as understanding how we fight infections.
Understanding Natural Killer Cell Development And Target Recognition
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Immune detection and eradication or control of cancer and cancer immunotherapies are based in part on the idea that tumour-specific white blood cells can protect the body from tumour development, growth and metastases. While strong evidence supports this, the means by which these white cells first recognize the cancerous tissue is largely unknown. We will study a new family of white blood cell receptors that may be important in this recognition, either naturally or following therapy.
The Role Of Stellate Cells In Fibrosis And Liver Disease Progression In HIV-Hepatitis B Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$157,292.00
Summary
Liver related mortality is the commonest cause of non-AIDS death in HIV infected individuals on treatment. With HIV, HBV liver damage is accelerated and liver-related mortality increased. Understanding how and why is critical to management. I will examine the role of hepatic stellate cells using in vitro models and directly ex vivo from infected patient biopsy tissue. I will investigate the activated of these cells by HIV and HBV infection, thus promoting scar formation with liver injury.
Defining The Interaction Of HIV With The Interferon System In Initial Mucosal Infection
Funder
National Health and Medical Research Council
Funding Amount
$867,716.00
Summary
Very early after virus exposure, immune cells secrete interferons that help limit the spread of viruses within the body. We will investigate the complex interplay between HIV and the interferon system, especially how HIV inhibits the early induction of interferon to aid its spread and then how the body later restores the interferon response. We will also examine how HIV manipulates the interferon system in order to persistent latent reservoirs within tissues.
Structural And Functional Studies Of The Human IL-3 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
This proposal will study a protein hormone that is implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine how the hormone receptor becomes activated, identify and characterise new agents that block this activation. This information will help in the development of new and highly specific drugs for use in certain cancers in inflammatory diseases.
Control Of Combined Simian-human Immunodeficiency Virus Infection Utilising NK Cells Mediating Antigen-specific Antibody Dependent Cellular Cytotoxicity - A Novel Vaccine Modality
Funder
National Health and Medical Research Council
Funding Amount
$432,587.00
Summary
Recently, progress was made in developing a vaccine against HIV. Our laboratory was selected to join a global collaboration trying to elucidate the key to this success. Attention has focused on non-neutralizing antibodies and our laboratory has developed a unique expertise in detecting such immune responses. This research will define, purify and manufacture these antibodies and test their ability to prevent HIV in animals with the ultimate aim of producing a vaccine for human use.