Induction Of Natural T-Regulatory Cells By Thymic Dendritic Cell Populations
Funder
National Health and Medical Research Council
Funding Amount
$413,775.00
Summary
In this study, we will determine the roles of the antigen presenting cells, namely denderitic cells, in the induction of T-regulatory cell (T-reg) developemnt in the thymus. T-reg cells play important roles in controlling the development of autoimmunity. This study will help to understand the possible causes of autoimmune diseases and to develop new treatments for these diseases.
Parkinson s disease (PD) is a progressively disabling movement disorder afflicting over 25,000 Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemcials and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration. Current symptomatic treatments give sufferers some relief for a period of time by boosting the amount of these depleted chemicals in the brain. Howe ....Parkinson s disease (PD) is a progressively disabling movement disorder afflicting over 25,000 Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemcials and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration. Current symptomatic treatments give sufferers some relief for a period of time by boosting the amount of these depleted chemicals in the brain. However, the underlying cellular degeneration continues unabated until such treatments are no longer effective. It is necessary to determine the reason for the cell loss in the brain in order to develop successful long-term treatments for this disabling disorder. There have been a number of animal models for PD developed. Comparing the type of tissue damage associated with the cell loss in these models shows that signs of brain inflammation occur prior to the loss of nerve cells. This feature consistently occurs regardless of the method used to produce the disease model. However, inflammation has been poorly studied in PD. Part of the present proposal is to analyse the brain tissue from patients with PD in order to document whether inflammation is also a consistent feature in the regions affected by the disease. Other central nervous system disorders in which inflammation is thought to play a pivotal role often have some genetic predisposition to the disorder and there is evidence of an immune response in their blood. We also wish to examine these aspects in patients with PD. Overall, our study will provide the necessary evidence for or against a primary role for inflammation in the disease process causing the ongoing degeneration in PD. If significant indications for a primary role for inflammation are found, treatments specifically targeting inflammation (already available) can be trialled to slow or stop the neurodegeneration.Read moreRead less
Co-ordinating The Intrinsic And Extrinsic Arms Of Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$615,286.00
Summary
The cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. The stem cell uses a handfull of important master-regulatory genes that act in a hierarchy to promote the blood cell differentiation process. 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.
Regulation Of Arthritis And Skin Inflammation By Annexin-1
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
Annexin-1, an antiinflammatory substance, mediates many of the actions of steroids. Our studies will reveal whether annexin-1 will reduce inflammatory and immune responses, and secondly, determine the substances regulated by annexin-1 in immune responses. If annexin-1 is found to mediate the immune regulatory effect of steroids, its capacity to be involved in the beneficial effect of steroids may have an important impact in treatment of arthritis and other inflammatory diseases.
Consequences Of Disulfide Exchange In CD4 For Function
Funder
National Health and Medical Research Council
Funding Amount
$332,580.00
Summary
CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells res ....CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells respond to infection and how the HIV virus infects immune cells. Moreover, we have designed a small synthetic compound that blocks the redox chemistry in CD4 and prevents HIV infection in the test tube. We propose to investigate how the redox chemistry in CD4 controls the function of immune cells and infection by HIV.Read moreRead less
UNDERSTANDING HEPATITIS C VIRUS-SPECIFIC T CELL TOLERANCE
Funder
National Health and Medical Research Council
Funding Amount
$429,710.00
Summary
Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have ....Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have the effect of inhibiting the immune response and result in the outcome that we currently recognise as persistent HCV infection.Read moreRead less
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
Regulation Of Monocyte And Macrophage Functions By Leucocyte Immunoglobulin-like Receptors (LILRs) In Human Colon
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
The human colon contains many bacteria that can invade through a damaged mucosal barrier and provoke immune cells to cause inflammation with their subsequent removal and a rapid shutdown of inflammation. Failure to clear bacteria or inflammation can lead to inflammatory bowel disease or sepsis. We will investigate how new proteins known as Leucocyte Immunoglobulin-like Receptors allow immune cells to effectively clear microorganisms without provoking uncontrolled inflammation
The Role Of The Dendritic Cell Surface Molecule Clec9A In Dendritic Cell Subset Function And Dead Cell Recognition
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Dendritic cells (DC) are sentinels of the immune system. DC monitor the environment and regulate tolerance to self versus immunity to dangerous material. Different types of DC perform different jobs. We have identified a new surface molecule, Clec9A, on some mouse and human DC. We will investigate the function of Clec9A in the immune response. We will also use Clec9A to help unite mouse and human DC biology, since until now there have been few useful marker molecules common to both species.
Immune Tolerance In Experimental Autoimmune Encephalomyelitis Following Transplant Of Bone Marrow Cells Genetically Encoding Autoantigen
Funder
National Health and Medical Research Council
Funding Amount
$339,143.00
Summary
Autoimmune diseases affect 5-6% of the population and include diseases such as multiple sclerosis. Our studies focus on examining a gene therapy approach together with bone marrow transplantation to treating autoimmune diseases. Using a model for multiple sclerosis we are finding promising results