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.
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.
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.
Investigating The Roles Of Non-coding RNAs In Inflammatory Signalling And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Inflammation occurs as part of the body's natural defenses against infection or injury, but can be damaging when unregulated and can lead to cancer. Although the protein factors critical for inflammation have been carefully studied it remains unknown how ribonucleic acid (RNA) molecules can modify and regulate inflammation. This project will identify RNA molecules that control inflammatory signalling, and further translate these findings to show they contribute to the progression of cancer.
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.
Il-18 helps to prevent obesity and type 2 diabetes, however the process by which this cytokine is activated to prevent obesity is not known. We have now found the pathway that drives to this process. This project will seek to extend our observations to show how this can be targeted therapeutically to treat obesity and type 2 diabetes.
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.
Understanding ILC1 Transcriptional Regulation And Function In Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Natural killer cells are innate cells that provide first line defense against infection and cancer. The recent discovery of a novel innate cell population has modified our vision of the early events necessary for immune protection. Understanding the role of these cells is critical as they could represent viable therapeutic targets. We have developed unique mouse models to experimentally target this population to determine how they are generated and their role in combating infection and cancer.