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.
Human Fc Receptors In Antibody Mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$640,824.00
Summary
A series of major Australian discoveries is leading to the development of therapies to treat major inflammatory diseases such as rheumatoid arthritis, lupus and similar autoimmune diseases where there is a significant unmet need for new therapies. A major molecule, caled Fc receptor was discoverd by the researchers who have now found new ways to prevent it activating inflammatory cells and therby preventi tissue destruction.
We have discovered how a rare type of human antibody called IgG4 exerts a major regulatory influence on the body's immune system. We have discovered how IgG4 can "switch" off inflammatory white blood cells which has broad implications for the development of new forms of therapy for switching off allergies and autoimmune diseases and for switching on immunity to infections and cancers.
Structural Studies On The Immune Effector Perforin: Developing Mechanism-based Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$1,116,594.00
Summary
Perforin is an essential weapon deployed by the human immune cells in order to destroy virally infected or cancerous cells. Despite this key role, unwanted or excessive perforin function can result in disease and can severely impact on successful treatment of leukaemia through bone marrow transplantation. This application aims to understand the molecular details of perforin function, and to apply this knowledge to develop perforin inhibitors.
Estimation And Partitioning Of The Still-missing Heritability For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$291,856.00
Summary
We have pioneered the use of multi-marker statistical genetic methods in human genetics to elucidate the genetic architecture of complex traits, including common diseases. We have shown that between a third and a half of additive genetic variation is captured by common genetic variants, leaving two-thirds to a half truly ‘missing’. In this proposal we will test our hypothesis that the still-missing heritability is due to low frequency causal variants. Applications of genomic medicine require thi ....We have pioneered the use of multi-marker statistical genetic methods in human genetics to elucidate the genetic architecture of complex traits, including common diseases. We have shown that between a third and a half of additive genetic variation is captured by common genetic variants, leaving two-thirds to a half truly ‘missing’. In this proposal we will test our hypothesis that the still-missing heritability is due to low frequency causal variants. Applications of genomic medicine require this fundamental knowledge to progress fully.Read moreRead less
Determining Regulators Of ILC3 In Mucosal Barrier Function And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$705,209.00
Summary
Innate lymphoid cells (ILCs) are specialized cells that defend the body against invading microorganisms at the body’s surfaces, mediate pathogen clearance and tissue repair but may also drive inflammatory conditions such as allergic asthma and inflammatory bowel disease. We will investigate the molecular switches that regulate this novel cell type and potentially uncover novel molecules or pathways for therapeutic targets.
The Role Of Cytokines In Tumor-induced Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$754,473.00
Summary
Cancer-induced immune suppression is a major obstacle to the effective treatment of many cancers. We have shown that the cytokine IL-23, plays an important role in cancer initiation, growth and development. My project aims to characterize the cells that produce IL-23 in the cancer microenvironment and define how it suppresses cells of the immune system. A greater understanding of this cytokine’s mechanism of action will enable the rational improvement of treatments for patients with cancer
Methods And Software Tool For Complex Trait Analyses Using Multi-omics Data
Funder
National Health and Medical Research Council
Funding Amount
$573,999.00
Summary
This project aims to develop methods to disentangle the contribution of people’s difference in DNA sequence, DNA methylation, and gene expression to their difference in characteristics (including risks to diseases), and to utilise these information to predict disease risks of different people. This project also aims to develop a versatile and efficient computer software to implement the methods being proposed in this project, as well as all other commonly used methods in the research community.
Deciphering The Role Of Intron Retention In Monocyte Differentiation And Function
Funder
National Health and Medical Research Council
Funding Amount
$511,114.00
Summary
In 2013, we made a breakthrough discovery that certain parts of genes, previously considered “Junk DNA”, are actually carrying signals to control the amount of proteins produced in cells. We now wish to understand the roles of these signals in the development of a key immune cell called monocyte. Monocytes are important to fight infection and inflammation in diseases such as diabetes and cancer. We hope to advance our knowledge on how we can manipulate these cells for therapeutic gain.