The immune system must be tightly regulated to make sure that it makes the right response to effectively fight off infection whilst avoiding inappropriate responses that cause damage such as in autoimmunity, inflammation or allergy. This project studies patients who have genetic defects that affect their immune systems and make them susceptible to infection and/or harmful immune responses. This will reveal some of the critical signals that maintain immune control.
CD8+ T cells provide us with protection against viruses and can also mediate potent anti-tumour effects. Understanding the signals that initiate and sustain an effective CD8+ T cell response is important if we are to intervene in diseases where CD8+ T cell function is defective. We will study patients with inherited gene defects that disrupt some of the signals that T cells receive to determine the role those signals usually play in instructing CD8+ T cells to fight viral infection.
Roles Of ID2 In Regulating Critical Innate And Adaptive Arms Of The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$597,418.00
Summary
The immune system protects us from a wide range of pathogens and foreign invaders. Natural killer (NK) cells and T cells are an critical component of the immune system due to their ability to detect and kill virally infected and malignant cells. Our work will endeavor to understand the molecular steps essential for these cells to develop and become armed to ensure immune protection.
A New Approach To The Design And Evaluation Of T Cell Vaccines For Cancer And Infectious Disease.
Funder
National Health and Medical Research Council
Funding Amount
$394,137.00
Summary
Special white blood cells called dendritic cells teach the immune system to fight cancer and are a key component of therapeutic cancer vaccines. We identified a subtype of human dendritic cell that is predicted to be the most effective at mounting anti-cancer immune responses. We developed a novel antibody specific for these dendritic cells that can be used to deliver the vaccine directly to them and will use this to construct and validate a novel vaccine for cancer and viral infections.
We will construct different genetically engineered viruses, which infect cells in the respiratory tract, to deliver genes encoding proteins from human immunodeficiency virus (the AIDS virus). These engineered viruses can be expected to generate an active immune response in mucosal tissues, including the vaginal and rectal tracts. As these are the major routes for transmission of the AIDS virus, these new vaccines are expected to reduce transmission of the AIDS virus.
The Role Of CCR6 In IL-17-producing CD8+ T Lymphocyte Activation And Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$514,041.00
Summary
T lymphocytes play an important role in the control of infection, but can also contribute to diseases such as autoimmune disease and cancer. This research will identify the function of a new subtype of T lymphocyte and determine whether inhibiting its function prevents disease.
The Opposing Genetic Networks Underlying Plasticity Of Humoral Responses
Funder
National Health and Medical Research Council
Funding Amount
$667,783.00
Summary
The immune system makes antibody to clear bacterial and viral pathogens. Specialised types of antibody are needed for different pathogens. This project will study genetic changes that determine the specificity of an antibody response. Regulation of these genes may prohibit production of antibodies and inflammatory mediators that attack the body rather than foreign pathogens. Understanding these processes will identify points of therapeutic intervention for patients with immune disorders.
Identification Of Haematopoietic Stem And Progenitor Cell Subpopulations
Funder
National Health and Medical Research Council
Funding Amount
$873,525.00
Summary
We want to dissect the machinery underlying how each and every individual stem and progenitor cell generates the different blood cell types. We have at our disposal the latest molecular and computational technologies to do this. Knowledge gained from this project could be used for tissue engineering to make blood cells on demand for patients with immune deficiency, or alternatively to treat leukaemia patients where blood cells are overproduced.
This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
Making Human T- And B-lymphocytes For Immunotherapy And Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$795,880.00
Summary
Lymphocytes are white blood cells that are involved in producing antibodies, killing defective cells, or killing cells infected with viruses. In recent years, researchers have found ways to harness lymphocytes to develop medicines for treating a variety of different cancers. In this project, we will establish methods to make human lymphocytes in the laboratory from stem cells, paving the way for the broader application of this cell type to new therapies.