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.
Second Trimester Intra-amniotic Treatment For Early Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$392,420.00
Summary
Preterm birth is the leading cause of neonatal death and disability in Australia today, with those born before 32 weeks' completed gestation at the highest risk. Preventing these early preterm births requires treatment of the causative uterine infection. This proposal is to conduct the first study of direct intraamniotic antibiotic treatment of uterine Ureaplasma infection in a clinically relevant, large animal model of second trimester pregnancy.
Identification Of Factors Critical For Maintenance Of The Epidermal Barrier
Funder
National Health and Medical Research Council
Funding Amount
$616,950.00
Summary
The human skin plays a crucial role in the body’s defence against our hostile environment. The outer most layer of the skin, the epidermis is the key structural component of the skin barrier and is essential for its integrity. We have identified a family of genes that are pivotal for epidermal barrier formation, maintenance and repair. This project examines the mechanisms that underpin the function of this family, and has broad ramifications in a host of dermatological conditions.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.
What Is The Molecular Mechanism Underlying Cell Death By Necroptosis?
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Recently, we and others have demonstrated that part of the MLKL protein is able to kill cells. This process is known to cause a number of pathologies, including those arising from stroke. Blocking this type of cell death has thus emerged as an attractive therapeutic strategy. However, precisely how MLKL kills cells remains unclear and controversial. In this project, we will resolve these controversies with the goal of an increased fundamental understanding to aid drug discovery.
Membrane-active Antibiotics Against Multi-drug Resistant Gram Negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$942,299.00
Summary
We are now threatened by bacteria that are resistant to ALL antibiotics. However, there is a new paradigm: antibiotics inspired by nature that attack the membrane of bacteria. This project will re-engineer peptides from lugworms, horseshoe crabs, scorpions and spiders that are part of nature’s ancient defence against bacteria, to identify new antibiotics to combat infections in humans.
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.
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