Delineating Aberrant Adaptive Immune Responses Due To Germline Mutations In The PI3K Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$975,476.00
Summary
Activation of immune cells is required to generate appropriate immune responses that protect is from disease caused by pathogens. The inability to receive the correct type of signals causes immunodeficiency. The PI3 kinase pathway is central to immune cell activation – and genetic errors in this pathwat compromise the functioning of immune cells. We will investigate the nature of these defects and pursue avenues of overcoming them using pharmacological inhibitors of the PI3K pathway.
The Role Of Cross-reactive T Cells In Severe Lung Disease Following Viral Respiratory Infections
Funder
National Health and Medical Research Council
Funding Amount
$1,003,390.00
Summary
Why do some patients clinically deteriorate at a greater rate than others during acute respiratory viral infections despite similar or identical clinical management? One explanation is the reactivation immunity towards ubiquitous viruses that then go on to cross-react against the new respiratory pathogen leading to an overly aggressive and destructive response in the lung. We will examine this potential of existing anti-viral immune responses to exacerbate disease in lung transplantation, as suc
Applying Quantitative Immunology To The Analysis Of Complex Genetic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$864,596.00
Summary
The immune response of each individual varies. For some, the response invoked by foreign challenge is weak, leading to a lifetime of difficulty with infection. For others, the response is stronger, yielding excellent immunity, but opening the potential for overactive responses to self-material and autoimmune disease. We have a new theory for how the health of our immune system can be measured and we aim to apply it to understand the genesis of the many different forms of human immune diseases.
The Axis Of Bcl-2, Plasmacytoid DCs And Lupus As A Basis For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$712,172.00
Summary
Systemic lupus erythematosus (SLE) affects 1 in 1000 Australians, mostly women. Here the immune system goes awry and makes antibodies against the body’s own components including the body’s DNA. This leads to damage to many parts of the body including kidneys, joints, brain and heart. It is incurable. A particular immune cell controls the development of this disease and we have found this cell is selectively killed by an inexpensive drug, which we hope will be a better way of treating SLE.
Generation Of Protective Immunity Against Severe Influenza Disease In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$1,630,970.00
Summary
Hospitalisation and death rates from influenza are high in the Indigenous population, especially when a new virus emerges. There is an urgent need for a vaccine that protects against all influenza strains. T cells recognising conserved viral regions elicit such protection. As T cells are restricted by proteins called HLAs, which vary across ethnicities, we will define T cell regions for HLAs prominent in Indigenous Australians and define how to generate protective immunity against influenza.
This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
MAIT cells are a recently discovered type of lymphocyte that plays a unique and important role in the immune system. However, these cells vary widely in number between healthy individuals, for reasons that are unclear. This project is designed to understand the factors that control the development of MAIT cells as a step toward regulating their numbers and activity.
CD4+CD8β+ Double-positive T-cell Regulation Of CD8 T-cell Responses
Funder
National Health and Medical Research Council
Funding Amount
$430,983.00
Summary
T-cells are a type of white blood cell that play an essential role in the immune system. CD4+CD8+ Double-Positive (DP) T-cells are a rare and poorly defined T-cell subset associated with skin disease - however their function and subsequently their contribution to disease is not known. Our preliminary data suggest that these DP cells may regulate the function of other immune populations in the skin. This project aims to deliver key insights into DP cells and their role in skin disease.
In this project, we will determine how a protein called ACKR4 suppresses antibody production and determine whether inhibiting its function will enhance the effectiveness of vaccination.
During an immune response a white blood cell, the T lymphocyte, receives a series of signals that manipulate cell survival and proliferation. The team at WEHI will identify the effects of key signals on the molecular control of T cell survival. The results will be used to test a new method for inducing tolerance and dampening unwanted immune responses, such as during tissue graft rejection and autoimmunity.