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.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.
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.
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.
The Role Of Rip3 And Caspase 8 In Necroptosis And Apoptosis During Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$459,499.00
Summary
Programmed cell death can be beneficial or detrimental depending on circumstances. This delicate balance is most obvious during an infection. The host tries to limit the spread of a pathogen by initiating programmed death in infected cells but excessive death particularly in uninfected cells is catastrophic. It is essential to have a thorough understanding of the interplay between cell death mechanisms so we can overt pathological outcomes and this is the focus of our research.
Construction And Immunogenic Evaluation Of Hepatitis B Virus Like Particles Expressing T And B Cell Epitopes Of Streptococcus Pneumoniae For The Prevention Of Hepatitis B And Pneumococcal Mediated Otitis Media In Australian Indigenous Children.
Funder
National Health and Medical Research Council
Funding Amount
$500,637.00
Summary
Australian Indigenous children suffer abormally high levels of middle ear infections (term otitis media). In many cases the infections become chronic and have a severe dischage. We propose to make a novel vaccine that will protect these children against a major bacterial cause of the ear infection as well as against hepatitis B virus infection as well.
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?
Modeling Human Actin Related Protein 2/3 Complex Subunit 1B (ARPC1B) Deficiency In Mice
Funder
National Health and Medical Research Council
Funding Amount
$755,005.00
Summary
The actin cytoskeleton forms the structure that not only keeps cells in their normal shape but is also essential for the movement of cells and for interaction between cells. We have recently identified the first patients with an immunodeficiency caused by a defect in a gene called ARPC1B, which plays a crucial role in the regulation of actin. Through the investigation of novel mouse models we will elucidate the pathomechanism underlying the disease of these patients.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.