Absence Of CC Chemokine Receptor 6 Dysregulates The Humoral Immune Response.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
The individual steps leading to the activation and differentiation of B cells and the formation of mature functional germinal centres have been investigated in detail and are well understood. In contrast, the underlying molecular signals, which regulate the different events and prevent either autoimmunity or immunodeficiency are still not fully comprehended. This proposal will address these regulatory steps that prevent autoimmunity.
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.
The Structure And Composition Of The T-cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
Our research will provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
Mechanism Of Epidermal Growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
This application examines the cellular events that control heart growth in response to angiotensin, a hormone linked to heart failure. We believe that the same cell processes are also involved in cancer cell growth and by understanding the mechanism by which angiotensin promotes growth, better therapies against human cardiovascular disease and its relationship to uncontrolled growth will evolve.
Cell Cycle Tracking Of B Cell Differentiation And Mutation
Funder
National Health and Medical Research Council
Funding Amount
$719,666.00
Summary
Antibody-mediated immunity to infectious diseases requires the proliferation of infection-specific antibody-producing B cells. The fate of responding B cells is linked to this proliferation according to a poorly understood division-based “map”. This project will track B cell fates in vivo using advanced imaging techniques. We will define differences between B cells from young versus old individuals that may explain why the effectiveness of the immune system declines with age.
Targeting Antigen To Clec9A On Dendritic Cell For Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$744,624.00
Summary
Dendritic cells capture infectious organisms and display them to other immune cells to initiate immunity. The process of capturing organisms requires dendritic cells to express a variety of cell-surface receptors that detect components carried by infectious agents. Here we will examine the efficacy of attaching vaccine components to a targeting agent that binds one of these receptors with the aim of enabling dendritic cells to efficiently kick-start immunity against vaccine components.
Worldwide >360 million people have chronic hepatitis B virus (HBV) infection that imparts a 25% lifetime risk of death due to serious liver disease. Current therapies for chronic HBV reduce levels of virus replication but fail to target the stable, nuclear episome, covalently closed circular DNA (cccDNA). The current study will determine what is required to eliminate cccDNA and how current therapies for chronic HBV infection should be modified to achieve this aim.
Regulation Of The Signalling Efficiency Of The T Cell Antigen Receptor
Funder
National Health and Medical Research Council
Funding Amount
$456,557.00
Summary
An immune response starts with activation of the T cell antigen receptor (TCR). How T cell receptor signalling begins, however, is not well understood. We have developed a novel imaging approach that allows us to directly observe what happens after an antigen binds to the receptor. The research will provide mechanistic insights into how T cells sense and discriminate antigens. This knowledge will aid the development of cancer immunotherapies and vaccines.
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.