Novel Approaches To Control Mast Cell Function In Allergic Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$723,447.00
Summary
Allergic disorders are a major health problem. Driven by mast cells, the underlying inflammation is exacerbated by the ‘?c family’ of cytokines acting on the surface of these cells. We aim to characterise the ‘mast cell-?c axis’ with the view to developing new therapies based on our ?c receptors blocking antibodies. This path of discovery-mechanism-translation seeks to recapitulate our previous success of taking a related antibody to Phase II clinical trials to treat patients with leukaemia.
Control Of Mast Cell Tryptase Function In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Allergic disorders such as anaphylaxis, eczema, hay fever and asthma affect about 25% of the developed world. Australia has one of the highest asthma prevalence in the world, costing Australians about a billion dollars a year. One of the central players in allergies is the mast cell enzyme, ?-tryptase. We have discovered a new mechanism of control of this enzyme. This research will aid the development of specific and potent inhibitors of ?-tryptase for the treatment of allergic disorders.
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.
S100 Proteins: Novel Oxidant Scavengers In Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$505,814.00
Summary
Allergic inflammation includes conditions such as dermatitis and asthma. Asthma, affects one in 10 adults and one in 6 Australians, costing ~$720 million/annum. We will characterize new mediators of oxidant defence which have suppressive effects on key pathogenic processes. The novel oxidative changes in S100 proteins may lead to new diagnostic reagents and new strategies for therapy. Results will open new frontiers in asthma biology and will apply to other chronic inflammatory diseases.
Mast Cells Are Key Negative Regulators Of Skin Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$687,519.00
Summary
Australians are at high risk of sun-induced skin cancer and skin damage caused by the harmful ultraviolet (UV)-B rays in sunlight. Our research focuses on understanding how skin mast cells act as part of the body’s natural defence against skin tumourigenesis caused by excessive UVB exposure or chemical insult to the epidermis. Understanding the innate mechanisms that protect against excessive skin damage and cancer might lead to better prevention and treatment strategies in the future.
Regulatory Roles Of Mast Cells In Cutaneous Dermatitis In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
Allergic conditions that can affect the skin, such as contact dermatitis or eczema are common amongst Australians. Although not life threatening, these common skin conditions can cause considerable physical diability and be expensive to treat. The major focus of our research is to define how dermal mast cells can be modulated to help limit the tissue changes and damage associated with these skin conditions, and ultimately develop improved treatments in the future.
Elucidating The Role Of Mast Cell Tryptases In Chronic Obstructive Pulmonary Disease And Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Smoking leads to inflammation that causes emphysema and inflammation in the lung and gut, which are major health problems. Once induced, there is a progressive decline in health and there are no effective treatments. Particular proteins and small genes have been discovered that control inflammation in these diseases. We may be able to control these proteins/genes and stop the progression of emphysema and gut inflammation. This project may lead to a completely new way of preventing and treating t ....Smoking leads to inflammation that causes emphysema and inflammation in the lung and gut, which are major health problems. Once induced, there is a progressive decline in health and there are no effective treatments. Particular proteins and small genes have been discovered that control inflammation in these diseases. We may be able to control these proteins/genes and stop the progression of emphysema and gut inflammation. This project may lead to a completely new way of preventing and treating these diseases.Read moreRead less
A Mechanotransduction Apparatus To Coordinate Epithelial Collective Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$994,596.00
Summary
Epithelial cells migrate as physically coherent collective groups, which is necessary for normal development and is disrupted as cancers progress to become invasive and spread. Collective migration requires communication so that the behaviour of individual cells is properly coordinated. In this project we investigate how the transmission of physical force between cells allows them to communicate; and test how its disruption contributes to cancer invasion.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.