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
Human Fc Receptors In Antibody Mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$640,824.00
Summary
A series of major Australian discoveries is leading to the development of therapies to treat major inflammatory diseases such as rheumatoid arthritis, lupus and similar autoimmune diseases where there is a significant unmet need for new therapies. A major molecule, caled Fc receptor was discoverd by the researchers who have now found new ways to prevent it activating inflammatory cells and therby preventi tissue destruction.
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.
We have discovered how a rare type of human antibody called IgG4 exerts a major regulatory influence on the body's immune system. We have discovered how IgG4 can "switch" off inflammatory white blood cells which has broad implications for the development of new forms of therapy for switching off allergies and autoimmune diseases and for switching on immunity to infections and cancers.
Investigating The Physiological And Biochemical Role Of SOCS5 In The Immune System
Funder
National Health and Medical Research Council
Funding Amount
$405,940.00
Summary
Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against paras ....Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against parasite infection. In other words, asthma is thought to arise through inappropriate IL-4 and IL-13 activity in the absence of a parasite infection. Extra IL-13 is commonly found in the lungs of asthmatics and is thought to help trigger asthma attacks. IL-13 is a validated target for drugs that could be used in the treatment of asthma. The SOCS genes were discovered in our laboratory and by genetically deleting the genes in mice we have demonstrated a critical role for SOCS1, SOCS2 and SOCS3 in regulating the immune response and the action of growth hormone. My hypothesis is that SOCS5 is an important physiologic regulator of the asthma response. This proposal will investigate the basic biochemical processes underlying the regulation of IL-4 and IL-13 action and the relationship to development of asthma and immune disease. I plan to induce asthma attacks in mice that lack the genes for SOCS4 and SOCS5. If the severity of the attacks is greater in the absence of these proteins this will indicate that SOCS4 and-or SOCS5 are important negative regulators of IL-4 and IL-13. This has the potential to open up a completely new strategy for the development of drugs that could be used in the prevention and treatment of asthma.Read moreRead less
Leukocyte Immunoglobulin-like Receptors Regulate The Function Of The Major Cells Involved In Allergic Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
An important aspect of the immune system is its ability to maintain a delicate equilibrium between the extremes of reactivity and quiescence. A break in this equilibrium can lead to unchecked activation of immune cells or inability of these cells to mount an effective defence. Potential outcomes of the unchecked activation of cells are autoimmune diseases such as rheumatoid arthritis or allergic diseases such as asthma. A new family of cell surface proteins termed leukocyte immunoglobulin-like r ....An important aspect of the immune system is its ability to maintain a delicate equilibrium between the extremes of reactivity and quiescence. A break in this equilibrium can lead to unchecked activation of immune cells or inability of these cells to mount an effective defence. Potential outcomes of the unchecked activation of cells are autoimmune diseases such as rheumatoid arthritis or allergic diseases such as asthma. A new family of cell surface proteins termed leukocyte immunoglobulin-like receptors (LIRs) has been shown to regulate immune cells by either increasing or decreasing their activity. In this project we will study the role of LIRs in regulating the activity of the major cells involved in allergy and asthma. This study would provide important insights to mechanism(s) of regulation of immune cell activation during protective immune responses such as the fight against infections and cancers and during pathological inflammations such as asthma and rheumatoid arthritis. Understanding the role of the LIRs in the regulation of immune cell activation might lead to new therapeutic strategies aimed at restoring the balance between the inhibitory and activating LIRs.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
Defining The Roles Of The Chemotactic Receptor EBI2 For The Regulation Of Leukocyte Migration And The Generation Of Immunity
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The proposed study aims at improving our understanding of the role of the immune cell receptor Epstein-Barr virus-induced gene 2 (EBI2) in guiding the movement of white blood cells during immune responses. The project will investigate the function of EBI2 in the control of infectious diseases and its regulation on human immune cells. These insights have the potential to create new therapeutic approaches to treat human autoimmune and inflammatory diseases and improve vaccine design.