A Novel Procedure For Efficacious Gonadotrophin-free Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$436,328.00
Summary
Infertility is common and is associated with health risks and is expensive. Using laboratory animals, we have developed a unique procedure, which has comparable success rates to IVF but crucially, it eliminates the need for ovarian hormone therapy used in IVF. A clinical trial using this method has started in Brussels and in this project we will examine cells from that trial and from animals to investigate the underlying mechanisms to enable safe and rapid clinical implementation.
IL-2-anti-IL-2 Complexes In Immunity To Blood Stage Malaria Infection And Prevention Of Cerebral Immunopathology
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Cerebral malaria is a severe complication of malaria infection, which accounts for a large proportion of malaria-related deaths each year. There is no vaccine against malaria licensed for use in humans. Trial vaccines have been shown to protect poorly against cerebral malaria, and have on occasion, increased the its incidence amongst experimental animals. We aim to develop a safe malaria vaccine that controls malaria parasite numbers in the body, and also prevents cerebral malaria.
Contribution Of Dendritic Cell Paralysis To The Immunosuppression Associated With Systemic Infections
Funder
National Health and Medical Research Council
Funding Amount
$490,051.00
Summary
The immune system fights viruses and other infections mobilising antibody-producing B cells and killer T cells. The B cells and killer T cells are recruited by specialysed cell of the immune system called Dendritic Cells (DC). The DC are distributed all over the body, where they play an immunosurveillance role: they constantly monitor their sorroundings for the presence of pathogens. When DC detect these pathogens they become activated . They capture the pathogen, break it into small pieces call ....The immune system fights viruses and other infections mobilising antibody-producing B cells and killer T cells. The B cells and killer T cells are recruited by specialysed cell of the immune system called Dendritic Cells (DC). The DC are distributed all over the body, where they play an immunosurveillance role: they constantly monitor their sorroundings for the presence of pathogens. When DC detect these pathogens they become activated . They capture the pathogen, break it into small pieces called antigens, and display these antigens on their surface, where they can be seen by helper T cells, which in turn mobilise the B cells, and by killer T cells. This chain of reactions initiates an immune response. The DC undergo profound changes after they detect pathogens. They stop monitoring their sorroundings, and concentrate on displaying to T cells the antigens that belonged to the pathogen that triggered their initial activation. Indeed, they do not respond to new pathogen encounters. In normal conditions few DC are activated by each pathogen encounter, so there are always enough DC ready to respond to new infections. However, there are situation that activate nearly all the DC at the same time. This can happen during sepsis (bacterial infection of the blood) and malaria. It has been recognised for a long time that these two conditions can be immunosuppressive they shut-down the immune system. Our previous work has demonstrated that this is in part due to the excessive number of DC that sepsis or malaria activate, leaving no more DC capable of responding to subsequent infections. This work has focused on the immediate effects of sepsis or malaria -within the first 24 hours or so; now we want to investigate the efffect of these conditions on the reconstitution of the DC network. We think this will help us to find treatments to restore immunocompetence a functional immune system- in sepsis or malaria patients.Read moreRead less
One in five Australian couples experience infertility and poor egg quality is a major contributing factor. Developing eggs in the ovary are surrounded by helper cells and we have discovered a new form of communication between these cells and the egg that regulates egg quality. This project will investigate the details of this dialogue and how it improves egg quality. New knowledge gained from this project will improve our understanding and treatment of infertility and reproductive diseases.
Discovery Of Long CD8+ T Cell Epitopes Uncovers A Hidden Reservoir Of Immunodominant, Anti-tumour Responses
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
Stimulating killer T cells to eliminate tumours has been one of the ultimate yet elusive goals of cancer vaccine development. Vaccines aimed at stimulating killer T cells are similar to those generated under natural conditions. However, special strategies are needed to vaccinate beneficial killer T cells that are not normally part of the natural immunity. In this project, we will explore such a scenario and dissect the related mechanisms contributing to such differential immune outcomes.
A Dendritic Cell Subset Targeting Approach For Generating Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$678,492.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
Regulation Of B Lymphocyte Survival And Tumourigenesis By The TRAF2-TRAF3-cIAP Signaling Complex
Funder
National Health and Medical Research Council
Funding Amount
$439,395.00
Summary
A major contributing factor in the development of cancer is the loss of the normal controls that regulate cell survival. We have identified a group of proteins that control the survival of B cells, the white blood cells responsible for producing the antibodies that fight infections. In this project we will investigate the mechanisms by which these proteins function and how inactivation of their functions can lead to multiple myeloma, an aggressive cancer of antibody producing cells.
Modulation Of Virus-cellular Receptor Interactions In Picornaviral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$422,036.00
Summary
Gastrointestinal viral infections of humans result in a wide variety of illnesses ranging from the common cold to infantile paralysis and viral myocarditis. Despite the wide range of tissues and organs targeted by these viruses, the manner in which infection is initiated is remarkably similar. The primary step in infection is the binding of a virus to a specific protein on the cell surface, similar to the lock and key analogy. This project seeks to investigate the nature of interactions between ....Gastrointestinal viral infections of humans result in a wide variety of illnesses ranging from the common cold to infantile paralysis and viral myocarditis. Despite the wide range of tissues and organs targeted by these viruses, the manner in which infection is initiated is remarkably similar. The primary step in infection is the binding of a virus to a specific protein on the cell surface, similar to the lock and key analogy. This project seeks to investigate the nature of interactions between representative picornaviruses and their cellular attachment proteins with a view to designing rational anti-viral strategies to block virus cell attachment and cell entry. Using the data raised when investigating why some viruses only infect certain cells, we plan to target human tumors cells based on their susceptibilty to different viruses.Read moreRead less
Probing The Cellular Functions Of The Translation Factor P97
Funder
National Health and Medical Research Council
Funding Amount
$370,307.00
Summary
The protein p97 takes part in the synthesis of cellular proteins from messenger RNA, a central step in gene expression. We will characterise p97 function as cells progress through their cycle of growth and division, and during responses to stress. Cellular stress is important in many diseases, such as viral infection, diabetes, heart disease, cancer, or complications during major surgery. Knowledge of p97 function may help us to better understand and treat these diseases.