Mechanisms Of Novel TLR9 Mediated Intraocular Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$442,244.00
Summary
Corneal opacities and scarring due to microbial and parasitic infections are a major cause of blindness globally. Novel studies in our lab have shown that topical application of bacterial/viral DNA alone to the cornea can cause previously unrecognised inflammation in the retina. Understanding the mechanisms of this retinal inflammation and how to block it may help in the design of novel treatments for a number of blinding conditions.
The Role Of IL-17 In Regulating Liver Macrophage Permissiveness For Leishmania Infection
Funder
National Health and Medical Research Council
Funding Amount
$655,082.00
Summary
Visceral Leishmaniasis is a disease of poverty in the developing world caused by Leishmania parasites, which live and replicate within host tissue macrophages. A cytokine produced by host cells, IL-17A impairs the ability of liver macrophages to control this infection, as mice that lack IL-17A have lower parasite burdens in the liver after experimental infection. We propose to investigate if IL-17A mediates this impaired control by tuning the permissiveness of host macrophages to infection.
Unconventional Mechanisms For Activating The NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$747,031.00
Summary
Many inflammatory driven diseases such as arthritis, atherosclerosis and septic shock are also associated with cell death. This project will identify, at the molecular level, how cell death signalling specifically acts to trigger pathological inflammation. As such, it will identify novel targets for the development of next generation anti-inflammatory drugs.
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 Dual-edged Sword Of Zinc As An Innate Immune Antimicrobial Weapon Against Uropathogenic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$784,428.00
Summary
Infectious diseases are a major global health threat, and urinary tract infections (UTI) are one of the most common infectious diseases. Most UTI are caused by uropathogenic E. coli (UPEC). In order to cause infections, UPEC must be able to overcome our body’s first line of defence, the innate immune system. This project seeks to understand how our innate immune system uses zinc to combat bacterial infections, and how UPEC is able to defend against such responses in order to cause disease.
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.
Characterization Of Human-specific Anti-microbial Pathways
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The immune system protects us against infectious disease by killing invading microbes or pathogens. Macrophages are white blood cells that are important for the recognition and destruction of pathogens. This project aims to investigate the role of certain genes, which are turned on in macrophages when they sense invading pathogens, in protecting us against infectious diseases such as tuberculosis and gastroenteritis.
Toll-like Receptors And Innate Immunity: Genes And Pathways Regulating Infectious And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$138,367.00
Summary
The innate immune system is the first line of defence against infectious diseases, but also contributes to the pathology of inflammatory diseases (e.g. rheumatoid arthritis). I study specific genes and pathways used by the innate immune system to (1) understand how the innate immune system prevents infections and how microorganisms overcome these defences, and (2) develop approaches to block inflammation. Outcomes may include new therapies for inflammatory and infectious diseases.
Enhancing Host Defence Against Intracellular Pathogens By Preventing INOS Interaction With A Negative Regulator, SSB-2
Funder
National Health and Medical Research Council
Funding Amount
$448,881.00
Summary
Secretion of nitric oxide (NO) gas by immune cells is a critical defence mechanism for the killing of intracellular pathogens. Production of NO within cells is regulated by the enzyme iNOS. We propose that preventing iNOS from interacting with its natural inhibitor protein (SSB-2) would allow enhanced and prolonged iNOS expression leading to increased NO and increased killing of pathogens such as the mycobacterium tuberculosis and the Leishmania parasite.