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
Squamous cell carcinoma of the skin is extremely common in Australia, resulting in disfiguring surgeries and deaths. Although cumulative sun exposure is important, some people are very susceptible, and we do not know why. This project hinges on the notion that skin cancer is a complex (many genes involved). We will utilize novel systems to harness this complexity to understand why some people are resistant and others very susceptible so as to design appropriate control measures and treatments.
Building Tissue Engineered Flaps For Surgical Reconstruction
Funder
National Health and Medical Research Council
Funding Amount
$548,453.00
Summary
As a result of serious trauma, burns or cancer surgery, large areas of new skin may be required. Of the three major skin layers - epidermal and dermal replacements are available clinically, but the third layer - the underlying fat tissue layer is yet to be developed. This project has devised a novel product to rapidly recreate the skin fat layer and additionally rapidly grow new blood vessels in these layers which will enable excellent skin coverage in all forms of major skin loss.
Brm And Brg-1 Protect From Ultraviolet Radiation-induced Skin And Ocular Damage
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Ultraviolet radiation within sunlight is the most important environmental hazard to which Australians are exposed. It causes cancers of the skin and eye, in addition to other forms of skin and eye damage. However sunlight also has health benefits such as vitamin D production. To protect our health from the sun we need to understand how it causes damage and the meachanisms involved. We have discovered a new pathway that we plan to study, called Brm and Brg-1, that provides protection from UV.