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 THE TETRASPANINS CD37 AND CD82 IN LEUKOCYTE MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$370,902.00
Summary
White blood cells must be able to migrate to fight infection. For instance, immune responses are started by the migration of one type of white blood cells to the lymph node. Also, once activated white blood cells migrate out of the circulation to the site of infection where they can kill bacteria and viruses. This grant studies 2 proteins that control white blood cell migration. These proteins may one day be targets for drugs that either promote immunity or reduce inflammation.
Mechanisms Of Alpha-hemolysin Induced Immunoevasion By Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$465,475.00
Summary
S. aureus infections represent a serious global health problem. Currently, no vaccination is available demanding a better understanding of the immune response against this bacterium. We will test the hypothesis that S. aureus alpha-hemolysin represses the migration of innate immune cells to sites of cutaneous infection resulting in diminished immunity. Unraveling the mechanism behind this phenomenon will pave the way to better prophylactic and therapeutic measures against S. aureus infections.
The innate immune response is our primary defence against infection, but must be controlled carefully to avoid chronic inflammation and autoimmunity. Studying tiny regulators of gene function called micro-RNAs and unique cellular pathways, we aim to understand the “big picture” of genetic regulatory systems in innate immunity to provide new insights into inflammation and infection, the genetic basis of diseases, and to identify new potential therapeutic targets, biomarkers and antiviral targets.
A Systems-biology Approach To Understanding The Beneficial Heterologous Effects Of Neonatal BCG Vaccination In A Melbourne-based Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$846,853.00
Summary
BCG vaccine (usually used to protect against TB) also enhances the immune system of young babies to protect them against infections other than TB. We have a large collection of blood samples from a study in which babies were randomised to be given BCG vaccine at birth or no BCG. We will use these to understand the immunological and molecular mechanisms by which BCG boosts the immune system to protect against infections other than TB.
Neutrophil Regulation Of Early Adaptive Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$613,273.00
Summary
The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammator ....The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammatory diseases.Read moreRead less
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.
Inhibition Of Necroptosis As A Novel Strategy For The Prevention Of Bronchiolitis And Subsequent Asthma
Funder
National Health and Medical Research Council
Funding Amount
$658,015.00
Summary
Severe virus associated bronchiolitis is a major cause of infant mortality and a risk factor for asthma. Using a mouse model, we have shown that virus infection causes tissue damage, leading to the release of 'danger' molecules that promote excessive inflammation and tissue remodelling. We have identified an important mechanism by which the danger molecules are released. We will now assess whether blocking this process ameliorates viral bronchiolitis and breaks its nexus with subsequent asthma.
The Identification And Characterisation Of A New DNA Receptor
Funder
National Health and Medical Research Council
Funding Amount
$656,498.00
Summary
The immune system has evolved to fight disease-causing microbes. First, it has to recognize that an infectious agent has invaded. To do this we have developed many probes (receptors) that sense microbial products. Detecting microbial DNA is a critical alarm bell. However, distinguishing pathogen DNA from our own DNA is difficult because both look alike. We have identified a new receptor that helps us identify bacterial DNA and alerts the immune system to the imminent danger.
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.