A Congenic Approach To Analysing The Genomic Control Of Innate Immunity In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$240,156.00
Summary
In addition to the lymphocytes, which are specialised white cells that can learn to defeat the infections that the body has been previously exposed, the body has a number of other defences. These non-learning systems have been honed by evolution and usually form an effective first-line of defence. This proposal deals with three: complement, and two highly specialised types of white blood cell, the Natural Killer cells and the NKT cells. The project will study mice especially bred to carry differ ....In addition to the lymphocytes, which are specialised white cells that can learn to defeat the infections that the body has been previously exposed, the body has a number of other defences. These non-learning systems have been honed by evolution and usually form an effective first-line of defence. This proposal deals with three: complement, and two highly specialised types of white blood cell, the Natural Killer cells and the NKT cells. The project will study mice especially bred to carry different versions of the genes which control these defences. Particular attention will be paid to their involvement in the autoimmune diseases, type 1 diabetes and lupus.Read moreRead less
NKT cells are a type of lymphocyte with the ability to prevent a broad range of diseases including cancer, autoimmunity, infection and graft rejection. Sometimes, NKT cells also cause diseases, including allergy and atherosclerosis. Therefore, the ability to modulate these cells an important health objective. This project will investigate how NKT cells become activated by studying their surface receptors and what these receptors interact with.
Improving Adaptive Anti-viral Responses: A Key To Eliminating Persistent Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$402,391.00
Summary
Cytomegalovirus (CMV) can cause a persistent infection that can result in adverse clinical outcomes. Our previous work established that suboptimal adaptive immunity is responsible for viral persistence. This proposal will define the defect in adaptive immunity, its causes and how to improve it. The understanding gained from the proposed studies will provide crucial information for the development of improved anti-viral therapies and vaccines.
Role Of NK Cell-dendritic Cell Interactions In The Induction Of T Cell Responses Involved In Malarial Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$338,154.00
Summary
Cerebral malaria is a devastating neurological syndrome. Recent data indicate that NK cells are involved in disease induction. NK cell function is controlled by receptors encoded by a genetic region named the Natural Killer Complex (NKC). We showed that the differential expression of NKC genes controls the degree of susceptibility to cerebral malaria. Here we will identify and characterise NKC receptors involved in pathogenesis and the mechanism by which these molecules mediate disease.
Mechanisms Of Virally-induced Immunosuppression: Effects On DC-NK Networks
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Cytomegalovirus (CMV) infection induces immunosuppression that often results in adverse clinical outcomes. Our previous work established that dendritic cells (DC), cells involved in the initiation of immune responses, are a principle target for CMV. This proposal will test the hypothesis that CMV-induced immunosuppression is mediated by viral interference with DC. Understanding the mechanisms involved in the induction of immunosuppression is a crucial step towards developing better therapies.
The Transcriptional Regulation Of Lymphocyte And Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$596,051.00
Summary
The distinct cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. An important characteristic of the stem cell is its ability to balance the need to proliferate and produce the distinct cell types (termed differentiation) and the need to maintain an adequate number of stem cells in their primitive state (termed self-renewal). The outcome of this balance is the production, throughout life, of an astounding number of cells that are requ ....The distinct cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. An important characteristic of the stem cell is its ability to balance the need to proliferate and produce the distinct cell types (termed differentiation) and the need to maintain an adequate number of stem cells in their primitive state (termed self-renewal). The outcome of this balance is the production, throughout life, of an astounding number of cells that are required to replace those lost each day. This feat is controlled by a handful of important master-regulatory genes that act in a hierarchy to promote the differentiation process. This tightly controlled and multi-step regulation is essential, as failure to coordinate blood cell production is the underlying cause of many blood cell cancers such as leukaemia as well as immune deficiency and anaemia. This research aims to understand how these master-regulators function in isolation and together in producing the white blood cells that are required for our immune response to microbes, vaccination and to prevent cancer.Read moreRead less