Many white blood cells have an innate ability to sense infection, and trigger inflammation to fight invading microbes. These innate immune cells use particular receptors to sense pathogens and we have now identified a new pathway that leads to the activation of one of these, known as Pyrin. Genetic mutations can activate this pathway, and our project will determine the molecular basis for this, and how it can be targeted to treat inflammatory disease.
Defining The Contribution Of Skin Gamma Delta T Cells To Cutaneous Immunosurveillance, Immunity And Disease After HSV Infection.
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
Herpes simplex virus (HSV) causes genital herpes and encephalitis. Disease is severe in the immunocompromised and the newborn. HSV enters through breaks in the skin or mucosa, where it first encounters gamma delta T cells. We have recently made the key finding that HSV can infect gamma delta T-cells shortly after inoculation. Here we will study how they contribute to the immune response when a virus enters the skin in mice and human tissues. This may lead development of new topical antiviral vac ....Herpes simplex virus (HSV) causes genital herpes and encephalitis. Disease is severe in the immunocompromised and the newborn. HSV enters through breaks in the skin or mucosa, where it first encounters gamma delta T cells. We have recently made the key finding that HSV can infect gamma delta T-cells shortly after inoculation. Here we will study how they contribute to the immune response when a virus enters the skin in mice and human tissues. This may lead development of new topical antiviral vaccines.Read moreRead less
The Role Of Perivascular Macrophages In The Regulation Of Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Neutrophils are key defenders against bacterial infections. In this application we will test the hypothesis that perivascular macrophages play a critical role in the recruitment of neutrophils to site of cutaneous infection, and that these cells are targeted and destroyed by bacterial virulence factors. Our studies will gain novel insight into the leukocyte homing paradigm and shed new light on the mechanisms of microbial immuno-evasion.
Modulating Inflammation As A Therapy For Harlequin Ichthyosis
Funder
National Health and Medical Research Council
Funding Amount
$718,739.00
Summary
Harlequin Ichthyosis is a severe inherited skin disease caused by mutations in a protein which regulates how skin cells control their levels of lipids. Treatments for this disease are limited and do little to improve patients condition. We believe we have found a new way to treat this condition by altering tissue inflammation. This grant will undertake important experiments aimed at developing new therapies for this currently incurable disease.
Mast cells (MC) are key regulators of chronic skin inflammation, such as atopic eczema, and can also give rise to a group of diseases called mastocytosis. How MC numbers are regulated in these conditions is poorly understood. We have identified a novel circulating precursor cell that gives rise to MC. We will determine the function of these precursors in skin diseases, including eczema and mastocytosis, with the aim to curtail the course of of these difficult-to-treat conditions.
Specific Targeting Of Nanosystems By Cutaneous Delivery
Funder
National Health and Medical Research Council
Funding Amount
$985,026.00
Summary
Substances have long been applied to the skin for therapeutic or cosmetic purposes, but the range of suitable compounds is limited. Consequently, there is a need for a wider range of compounds which can be delivered effectively into the skin for targeted treatment, diagnostic imaging and vaccination. New nanomaterial drug delivery systems are being increasingly used for these purposes. We seek to understand the properties of nanosystems that will enable improved drug targeting via the skin.
INSIDE THE SKIN: UNDERSTANDING DIFFERENT HOST RESPONSES IN SCABIES
Funder
National Health and Medical Research Council
Funding Amount
$499,095.00
Summary
Scabies is an underlying cause of poor health in indigenous communities worldwide. Crusted scabies is a poorly understood, life-threatening form of the disease compromising the success of community control strategies. This research compares the immune response in the skin of scabies patients, and in a world-first animal model of human scabies. This will reveal specific immune defects predisposing to disease, ultimately resulting in improved skin health for disadvantaged communities
The Role Of Redox-related Post-translational Changes Of Complement Factor H (CFH) In Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$652,019.00
Summary
Patients with AMD experience loss of central vision and this disorder is the leading cause of blindness in those aged over 50 years in Australia. There are currently no effective treatments for dry AMD. We have identified a protein that undergoes a modification in the blood and the eyes of humans with AMD that has given us new insights into how AMD develops. Specific therapies targeting this modified protein may offer a new treatment for this important cause of blindness.
Determine The Role Of The SAA-Macrophage Axis On Respiratory Pathogen Clearance In Smoke Exposure Related Lung Disease.
Funder
National Health and Medical Research Council
Funding Amount
$617,810.00
Summary
Direct or second hand exposure to tobacco smoke significantly increases your risk of acquiring a chest infection. Infants and elderly smokers are particularly susceptible. This will continue to be a major global problem as household smoke exposure remains high in developing countries and disadvantaged indigenous communities. We will investigate how smoke alters important immune cells that normally clear lung infections, which may lead to completely new ways of treating chest infections.
Identification And Therapeutic Modulation Of Sphingolipids As Novel Lung Macrophage-targeted Treatments For COPD/emphysema
Funder
National Health and Medical Research Council
Funding Amount
$694,704.00
Summary
COPD/emphysema is predicted to be the third leading cause of death woldwide by 2010. We have shown defective lung macrophage function in COPD and have shown that we can modify the macrophage function with novel therapies. We are now investigating a specific “sphingosine” pathway to see if it can provide us with more specific information. We aim to provide a better, more specific, adjunct treatment for the disease.