Upregulation Of Chemokine Receptor Expression And Function On CD4+ T Cells In Primary And Secondary Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the bod ....This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the body is controlled. A better understanding of this process shuld allow us to design better ways to control it, thereby controlling the negative aspects of T lymphocyte activation.Read moreRead less
Regulation Of The Anti-tumour Immune Response By The Chemokine Decoy Receptor CCX-CKR
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Melanoma is a significant cause of cancer-related deaths in Australians. Death is usually due to metastasis of the cancer to the lungs and other organs. In this project, we will take advantage of unique mouse models to determine whether inhibition of the function of a novel protein can prevent melanoma growth and metastasis to different organs. The results of this study may lead to new therapeutic approaches to control malignant melanoma and other metastatic cancers.
Studies On The Role Of The P101 Component Of The Class 1B PI 3-Kinase In Cell Migration And Activation.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
This research will determine the biological role of a protein of unknown function that is likely to participate in movement of white blood cells through the body. The outcome of this research will increase our basic knowledge of how the immune system functions and could lead to alternate therapeutic strategies for the control of autoimmune diseases.
Polarity Regulation In T Cells: Mechanisms And Consequences.
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Advances in our understanding of how the immune system works have led to many breakthroughs in healthcare, including organ transplantation, management of autoimmune diseases and immunodeficiencies such as AIDS. To improve these treatments, we need a better understanding of how the immune system is controlled. This proposal explores the mechanisms by which immune cell signalling is regulated by spatial compartmentalisation within the cell.
The Appendix In Intestinal Immunity And Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects ....Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects against the later development of ulcerative colitis and probably Crohn s disease. If IBD does develop following earlier appendicectomy, it tends to be less severe. In this project, we plan to examine the immune features of the appendix, in human and mouse. The appendix is a major source of immune cells in the intestine but the nature of these cells and their functions are poorly understood. The aims of the project will explore the nature of immune cells, known as T lymphocytes, isolated from human and mouse appendices. Changes with age will be examined, to explain the age-related nature of the appendicectomy-IBD link. Anti- and pro-inflammatory characteristics of the cells will be studied, the migration pathways of these cells from appendix to other parts of the intestine will be clarified, and the therapeutic potential of these T cells in a mouse model of IBD will be elucidated. In addition, this will be the first study to develop and analyse a mouse model of appendicitis, which is very poorly understood. These studies will make important observations relevant not only to IBD, but to the immune function of the intestine, with implications for our fundamental understanding of the way we are protected from our hostile environment.Read moreRead less
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.
Chemokine Gradients For Directed Migration Of Captured Cells The And Guidance Of Tissue Engineering
Funder
National Health and Medical Research Council
Funding Amount
$711,643.00
Summary
Many diseases feature migration of cells along tissue gradients of molecules. We propose to create and characterise an artificial system in which we will design flat surfaces coated with varying densities of different molecules. We will study attachment and movement of cells along fixed gradients established by these surface coatings. These cells include lymphocytes that respond to infections and vaccines, cancer cells that invade and spread, and endothelial cells that form blood vessels.
Role Of The Thymus In T Cell Homeostasis During Foetal And Postnatal Life In Sheep
Funder
National Health and Medical Research Council
Funding Amount
$264,750.00
Summary
The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool e ....The mature T cell pool can arise from only two sources, either thymic export or expansion of the peripheral T cell pool or a mixture of both. The lifespan of either cell type, i.e. recent thymic emigrants or mature T cells, has considerable implications for the development of a pool of T cells able to respond to a large number of infections. Recent thymic emigrants represent a wide diversity of positively selected thymocytes exhibiting newly arising T cell specificities, but mature T cell pool expansion results in reduced diversity because of a predominant expansion of a limited number of clones. It follows that a mixing of the pool of older mature T cells with new ones just released from the thymus will introduce more variability, and hence greater adaptability into the immune system. We have developed techniques for labeling the thymus in vivo and the entire blood leukocyte pool in vivo using the long-term lymphocyte tracking dye CFSE. We can establish a cohort of labeled cells and we can, for the first time in any experimental system, track directly the survival, death or division of recent thymic emigrants and mature cells and their progeny together with their tissue homing properties and surface markers for periods of many months. This will enable us to determine the way in which the pool of mature T cells is built up during the formation of the foetal immune system and the way the mature T cell population is established and maintained in postnatal life.Read moreRead less