The Role Of The Transcription Factor IRF4 In Peripheral Cd8 T Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$399,176.00
Summary
T cells protect against viral infections and fight cancer cells. In order to fulfill these roles T cells have to undergo significant phenotypic and functional changes. Our preliminary data indicate a central role for the regulator protein IRF4 in this process, as T cells that lack this protein are unable to grow and acquire the cellular tools necessary to provide protection. We wish to characterize the role of IRF4 in T cells in detail and aim to identify the processes regulated by IRF4.
Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Towards A Functional Cure For HBV: Exploiting Lessons From HBV-HIV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$913,551.00
Summary
Hepatitis B virus (HBV) infection can be treated, but therapy is usually lifelong and has side effects, so a cure for HBV is very important. We work closely with colleagues in Asia where both HBV and HIV are common so this provides a unique opportunity to study HBV. We will investigate how an effective immune response against the 2 main HBV proteins is developed. If we can understand how the immune response works against HBV, this could be used to develop new therapies to develop a cure for HBV
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.
Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
Antigen Receptor As Oncogene: Understanding CARD11 Mutations In B Cell Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$607,395.00
Summary
More than 5000 Australians are newly diagnosed as lymphomas. Recent technology identified many candidate genes for lymphomas, however it still remains unclear how each mutated gene distorts signalling molecules inside tumours cells. By introducing one of recurrent mutated genes, CARD11 into mouse B cells, we will examine how this mutation affects normal signalling pathways and B cell functions. We hope this project will provide a guidance to use forthcoming drugs to target specific molecules.
B Cells And Autoantibodies In The Pathogenesis Of Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$853,340.00
Summary
This project aims to gain a better understanding of the causes of hypertension. Specifically, we will test the idea that activation of the immune system and the production of antibodies is a major cause of the blood vessel and kidney damage that leads to high blood pressure. Such findings could pave the way for new treatment approaches where drugs currently reserved for patients with autoimmune diseases (e.g. rheumatoid arthritis, gout) are re-purposed for the treatment of hypertension.
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.
VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.
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.