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The Mechanism For Combined Immunodeficiency And Autoimmunity Due To STK4-deficiency And Its Broader Application To Human PIDs
Funder
National Health and Medical Research Council
Funding Amount
$648,371.00
Summary
Why do some patients develop autoimmune diseases such as lupus where the immune system makes antibodies that attack its own body? To answer this, we plan to study a disease where a gene responsible for making antibodies is defective. Patients with mutations in the STK4 gene are unable to regulate the selection processes by which only the right cell is chosen to make antibodies. Understanding how STK4 works may help us unlock the mystery of what causes lupus.
Determining The Unique Processes That Control Memory B Cell-mediated Secondary Antibody Responses
Funder
National Health and Medical Research Council
Funding Amount
$853,644.00
Summary
Vaccines educate the immune system by training memory cells to make neutralizing antibodies when it re-encounters the pathogen. However, where and how these memory cells are activated in the secondary antibody response in immune animals remain unknown. Here we use cutting edge technologies to fate map and gene profile memory cells and determine the molecular switches that control the secondary antibody response. This will be complemented by human vaccine studies.
The Regulation Of B Cell Differentiation And Survival In Response To Antigen Challenge
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
Antibodies are crucial to health and well being but can cause disease if their production is not controlled appropriately. This research program examines the basis of antibody production in normal situations and in situations where it is causing illness, in diseases like system lupus erythematosus (SLE) and in cancers of antibody producing cells called multiple myeloma (MM). The aim is to enable control of the process to achieve better health outcomes and better management of disease.
IL21, B-cell Proliferation And The Mechanism Of Memory Formation
Funder
National Health and Medical Research Council
Funding Amount
$981,896.00
Summary
Our immune system can ‘remember’ old infections, which is why we do not suffer from the same pathogen multiple times and why vaccines work. Much of this protection is due to memory B-cells, of which there are different kinds. We think the different memory B-cell subsets have different functions and understanding how they are made and how this is controlled will help us improve responses to critical infections – HIV, Flu – and in critical patient groups – aged people and transplant recipients.
The Control Of Autoimmunity Originating From Somatically Hypermutated B Cells
Funder
National Health and Medical Research Council
Funding Amount
$530,337.00
Summary
Our immune systems are capable of producing long-lived antibodies that can last a lifetime. Sometimes, this powerful process can however become abnormal and result in autoimmune diseases such as lupus. We have recently developed the first experimental mouse model that allows researchers to study this process in great detail. This funding will extend our initial observations by identifying the exact mechanisms by which important regulators of autoimmune disease act.
Dynamic Imaging Of The Immune Response In Lymph Nodes By Two-photon Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$79,514.00
Summary
Despite the enormous contribution of vaccination to the prevention of human disease and suffering, little is known about the laws that govern the selection and survival of B cells during the response to infection or vaccination. Our research projects aim to integrate several cutting-edge technologies, including two-photon microscopy, in order to understand the cellular and molecular basis of immunity.
Manipulating Antibody Production To Maximise Memory In Vaccine Responses
Funder
National Health and Medical Research Council
Funding Amount
$1,084,424.00
Summary
Our immune system provides protection from germs. The secretion of germ-specific proteins (antibodies) is an integral component of this defence and the basis of virtually all vaccines. Pandemics of Influenza and SARS-CoV-2 and failure to develop vaccines against HIV and Malaria remind us that our strategies need urgent improvement. Increasing our understanding of how our body defends us by specifically targeting foreign structures will reveal avenues for successful, rational vaccine development.
Germinal Centres, Rogue B Cells And The Genesis Of Immunological Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$753,300.00
Summary
This study will determine how the immune system is normally prevented from producing autoantibodies that target the body's own cells and how this fails in autoimmune diseases such as lupus. Targeted studies of a newly discovered "rogue" white blood cell will also provide new clues on how autoimmune diseases arise. In addition, modeling of human immunological disease in mice via CRISPR/Cas9 mutagenesis will provide valuable new insights into their causes and potential treatments.
Discovering Molecular Signatures Of Human T Follicular Helper Cells And Antibody Producing B Cells To Improve Vaccine Efficacy And Transplation Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
A key way the body can fight off infections is to produce antibodies, a process that requires the coordinated efforts of multiple types of specialised immune cells. A more detailed understanding the factors that govern robust antibody responses is critically needed and will be investigated in this project in the context of vaccination and transplant rejection.