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.
Dynamics And Mechanisms Of Immune Complex-mediated Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,467.00
Summary
Type III hypersensitivity underlies a number of common autoimmune diseases, including rheumatoid arthritis and lupus erythematosus. These diseases are caused by the deposition of immune complexes (IC) and the accumulation of neutrophils within small blood vessels. We will use real time imaging to dissect in space and time the recruitment of neutrophils and IC deposition during type III hypersensitivity reactions in order to better understand the pathogenesis of these conditions.
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.
Analysis Of Antigen Receptor Sharing By T And B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
To survive an infection the immune system must rapidly expand the number of immune cells that have pathogen-specific receptors that recognise, and therefore specifically combat, the infection. This normally occurs through proliferation of the immune cells. We have found that in addition to proliferation, the number of cells with these receptors can be increased by a process of receptor transfer between cells. This grant aims to further advance our understanding of this novel phenomenon.
Determining The Role Of DOCK8 In CD4+ T And B Cell Differentiation And Its Implications On Autosomal Recessive Hyper IgE Syndrome (AR-HIES)
Funder
National Health and Medical Research Council
Funding Amount
$512,600.00
Summary
Autosomal recessive hyper IgE (AR-HIES) syndrome due to mutations in DOCK8 is a rare primary immunodeficiency whereby patients present with susceptibility to severe and recurrent viral infections as well as an increased risk of developing cancer, severe food and environmental allergies, and atopic disease characterised by hyper IgE and extreme eosinophilia. This grant will investigate how abnormal DOCK8 function in CD4+ T cells and B cells contributes to disease pathogenesis in AR-HIES patients.
Cytotoxic lymphocytes are immune cells responsible for the killing infected or cancerous cells. How cytotoxic lymphocytes mature from a naive inactive to a fully activated state as they encounter infected or malignant cells is poorly understood, and will be investigated in the current proposal. Our results will aid in the development of novel therapies for cancer and other immunological diseases.
Cellular And Molecular Characterization Of Erythroid Enucleation
Funder
National Health and Medical Research Council
Funding Amount
$671,950.00
Summary
A major challenge for transfusion medicine is the constant difficulties in obtaining enough supply of specific red blood cell (RBC) subtypes. In this proposal, we will identify the key steps of enucleation (extrusion of nucleus), a rate limiting process for the in vitro production of RBCs. A better understanding of this process will lead to improved strategies for the efficient and rapid production of self-generated RBCs for individual patient transfusion.
Host Metabolism And Responses Contributing To Flavivirus Replication And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$592,772.00
Summary
We aim to determine how viruses affect the cells they infect, In particular how they can alter the metabolism and balance of lipids in cells and how this impacts the bodies capability to respond immunologically. We believe that by understanding these basic principles we can target ares fr antiviral therapeutic potential.
Investigating The Cellular Response To Iron-Depletion: The Trilogy Of ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$552,572.00
Summary
Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for t ....Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.Read moreRead less
Understanding The Role Of CD4 T Cells In Viral Infection: A Means Of Improving Anti-viral Immunotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$672,009.00
Summary
Development of therapies to prevent and treat chronic infections is of the highest priority as they cause considerable clinical challenges and on-going health care costs. Efforts to improve treatment of chronic viral infections, such as those caused by HIV, hepatitis C virus and human cytomegalovirus, require a better understanding of the immune responses needed to control these viruses long-term. This proposal will investigate the role of CD4+ T cells in controlling chronic viral infection.