Molecular Cloning And Expression Of Cytokine Genes Related To Induction Of Allograft Transplantation Tolerance In Rats
Funder
National Health and Medical Research Council
Funding Amount
$212,371.00
Summary
Cytokines are soluble proteins produced by leucocytes, and in many cases other cell types, which act as chemical communicators between cells, but not as effector molecules in their own right. Most of the cytokines are growth or differentiation factors and they generally act on cells within the haematopoietic system. In this grant application we will focus on the production of cytokines and antibodies to these cytokines, that are likely to be important in organ transplantation tolerance or organ ....Cytokines are soluble proteins produced by leucocytes, and in many cases other cell types, which act as chemical communicators between cells, but not as effector molecules in their own right. Most of the cytokines are growth or differentiation factors and they generally act on cells within the haematopoietic system. In this grant application we will focus on the production of cytokines and antibodies to these cytokines, that are likely to be important in organ transplantation tolerance or organ rejection. We would like to synthesize these cytokines using molecular biological techniques. These biological materials will be used to treat animals and study their biological effect on transplanted graft survival. If the cytokine treatment does prolong graft survival, what is the mechanisms involved in the immune responses will be further studied. Our aim is to develop strategies that couold be applied to help pateints with organ transplants and receive most specific therapies.Read moreRead less
Glomerulonephritis (Bright's Disease) is the commonest cause of destruction of kidney function that leads to patients requiring artificial kidney treatment (dialysis) and renal transplantation. The glomeruli or filters of the kidney are attacked by inflammation and destroyed. The attack is usually auto-immune, that is the bodys' immune system loses tolerance to kidney tissue and mounts a destructive attack on the glomeruli. In many patients, this attack is mild and resolves with current treatmen ....Glomerulonephritis (Bright's Disease) is the commonest cause of destruction of kidney function that leads to patients requiring artificial kidney treatment (dialysis) and renal transplantation. The glomeruli or filters of the kidney are attacked by inflammation and destroyed. The attack is usually auto-immune, that is the bodys' immune system loses tolerance to kidney tissue and mounts a destructive attack on the glomeruli. In many patients, this attack is mild and resolves with current treatments to dampen the immune response. In others, current treatment is inadequate to dampen the attack and the kidney is destroyed. This research uses experimental models of nephritis to examine how the immune system injures the glomeruli. In particular, how T cells attack and mediate injury. This is a novel concept, as hither to it has been thought antibodies and other factors in the blood (complement) mediate injury. Our group was one of the first to identify T cells mediate injury in forms of glomerulonephritis, previously thought to be solely mediated by antibody and complement. This project will further define which molecules produced by the T cell effect injury of glomeruli. With the potential aim of turning off the T cell attack mechanisms in a more specific way than is achieved by non specific immunosuppressive drugs such as corticosteroids, cytotoxic (anti-cancer) drugs or cyclosporine (an anti-rejection drug). A major part of this project will be to examine the role of cytokines, hormone like molecules that are produced by white cells and mediate injury or regulate other white cells, in effecting injury and in turning off the immune injury.Read moreRead less
Regulation Of Macrophage Function And Gene Expression By The Th2-Promoting Stimulus, ES-62
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to c ....White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to certain diseases including asthma and diseases associated with intracellular infections. We are identifying genes expressed in macrophages during these immune responses that are likely to be involved in susceptibility to such diseases.Read moreRead less
Understanding The Pharmacology Of G-CSF For Treating Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$429,393.00
Summary
Heart attacks remain the most common cause of heart failure. Unlike many other tissues the heart is unable to repair itself. Recently it has been recognised that bone marrow cells promote to a small degree repair. Our research confirms these findings and indicates that these can be affected by substances that increase the circulating bone marrow cell numbers. This project will explore how bone marrow cells improve repair and ways to further improve efficacy.
Hematopoietic Cytokines For The Repair Of Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$334,375.00
Summary
Heart attacks remain one of the most common causes of heart failure. Unlike many other tissues such as the skin or bone marrow, the heart is unable to repair itself following a heart attack. Recently it has been recognised that bone marrow cells can to a small degree repair the heart. How this is done is not known but it may be due to the formation of new blood vessels and perhaps new heart muscle. Unfortunately, the repair by bone marrow cells is not very efficient. One way of improving the eff ....Heart attacks remain one of the most common causes of heart failure. Unlike many other tissues such as the skin or bone marrow, the heart is unable to repair itself following a heart attack. Recently it has been recognised that bone marrow cells can to a small degree repair the heart. How this is done is not known but it may be due to the formation of new blood vessels and perhaps new heart muscle. Unfortunately, the repair by bone marrow cells is not very efficient. One way of improving the efficiency of heart repair by bone marrow cells is to give people bone marrow growth factors that increase the number of bone marrow cells in the blood and thus, increase the number at the site of heart injury. Our preliminary research shows that this is the case although the efficiency of repair is still not enough as a useful therapy. This project will examine how bone marrow growth factors improve heart repair following heart attacks and explore ways of improving the efficiency of repair to permit trials in humans.Read moreRead less
The Study Of T Cell Differentiation And Function Using DNA Microarrays
Funder
National Health and Medical Research Council
Funding Amount
$155,665.00
Summary
The immune system uses specialized cells to combat various infectious agents, such as viruses or large parasites. The immune system remembers such pathogens, and is able to mount an enhanced and more rapid response upon secondary encounter. This property, termed immunological memory, is the basis of vaccination. Sometimes the normal functioning of the immune system goes awry, producing allergic disease (such as asthma) or autoimmune diseases (such as Multiple sclerosis and possibly rheumatoid ar ....The immune system uses specialized cells to combat various infectious agents, such as viruses or large parasites. The immune system remembers such pathogens, and is able to mount an enhanced and more rapid response upon secondary encounter. This property, termed immunological memory, is the basis of vaccination. Sometimes the normal functioning of the immune system goes awry, producing allergic disease (such as asthma) or autoimmune diseases (such as Multiple sclerosis and possibly rheumatoid arthritis). The nature of the cells that mediate immunological memory, or the processes that lead to inflammatory disease are poorly understood. A new approach towards understanding the function and inter-relationships of T cells is to use genomics techniques, that enable tens of thousands of genes to be assessed for their expression in different cells or tissues. An understanding of which genes are inappropriately turned on in different disease states should provide new understanding of disease process, and new targets for pharmaceutical intervention. We will systematically assess gene expression in various subsets of T cells, which have known functions. For instance Th1 cells have been implicated in the pathogenesis of autoimmune disease, and Th2 cells in the pathogenesis of asthma. How these cells regulate gene expression during their differentiation, and use their newly expressed genes for their specific functions is one aim of this study. Another important subdivision of the immune system is between skin homing and gut homing T cells. Gut homing T cells are thought to mediate protection in the gut against gut pathogens, but also to cause diseases such as inflammatory bowel disease (Ulcerative colitis, Crohn's disease). Finally, understanding which cells harbour immunological memory, and how this might be manipulated to improve immune resposes, is of great importance for vaccination programs.Read moreRead less
Unraveling IL-1F7: A Neglected IL-1 Family Member With Big-Stage Potential
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
Cytokines are messenger proteins used by most cells of the body. Since their role as master regulators of many biological processes was discovered, cytokines have enjoyed the limelight of biomedical research. Anti-inflammatory cytokines are particularly coveted as they could replace side effect-prone anti-inflammatory drugs like aspirin. We identified an anti-inflammatory cytokine (IL-1F7) and revealed its protective activity in common, severe diseases like myocardial infarction. We will now exp ....Cytokines are messenger proteins used by most cells of the body. Since their role as master regulators of many biological processes was discovered, cytokines have enjoyed the limelight of biomedical research. Anti-inflammatory cytokines are particularly coveted as they could replace side effect-prone anti-inflammatory drugs like aspirin. We identified an anti-inflammatory cytokine (IL-1F7) and revealed its protective activity in common, severe diseases like myocardial infarction. We will now explore how IL-1F7 exerts is protective properties.Read moreRead less
Macrophage Migration Inhibitory Factor (MIF): Pathological And Therapeutic Significance In Post- Infarct Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$547,577.00
Summary
Ischemic heart injury mediated by the inflammatory response has a significant impact on the prognosis. MIF is a central factor mediating and amplifying the inflammatory response but its role in heart disease remains largely untested. This project will study, for the first time, the crucial role of MIF in ischemic heart disease and will establish important experimental evidence for developing new anti-inflammation therapeutic strategies against ischemic heart injury.