Bcl-2 Proteins And The Regulation Of The Megakaryocyte Lineage.
Funder
National Health and Medical Research Council
Funding Amount
$416,240.00
Summary
Platelets are tiny cells that circulate in the blood. They are essential for blood clotting. Too few platelets leads to uncontrolled bleeding. Platelets are produced in the bone marrow by cells called 'megakaryocytes'. Cancer chemotherapy often causes dangerous decreases in platelet count - this is thought to be because it kills megakaryocytes. We will pinpoint the molecules responsible for megakaryocyte life and death. This has the potential to make the side effects of chemotherapy less severe.
Structure And Function Of Receptors For IgG (FcgammaR)
Funder
National Health and Medical Research Council
Funding Amount
$748,500.00
Summary
How FcR function in normal and destructive immunity: This research project is studying one of the most important receptor families of inflammatory white blood cells known in immunology. These receptors called Fc Receptors (FcR) bind complexes of specialised proteins called antibodies with foreign antigens, i.e. bacteria, viruses, called immune complexes. As a direct consequence of this binding, a chain of events in inflammatory white blood cells is set in motion, leading to the destruction of fo ....How FcR function in normal and destructive immunity: This research project is studying one of the most important receptor families of inflammatory white blood cells known in immunology. These receptors called Fc Receptors (FcR) bind complexes of specialised proteins called antibodies with foreign antigens, i.e. bacteria, viruses, called immune complexes. As a direct consequence of this binding, a chain of events in inflammatory white blood cells is set in motion, leading to the destruction of foreign pathogens, however in autoimmune diseases this same processes leads to the severe inflammation causing destruction of joints in rheumatoid arthritis and kidneys in glomerulonephritis or allergies, bleeding disorders. Our studies are aimed at understanding the very first events that initiate this inflammatory cascade, i.e. how immune complexes bind to FcR and having bound these, how these receptors are organised to initiate the inflammatory cascade. Our studies will use new techniques such as X-ray crystallography to take 3D photographs of FcR interacting with immune complexes and genetic engineering studies to validate our 3D photographs. If we understand how immune complexes bind to FcR and how the receptors are organised on the cell membrane, we will be able to apply this information to the development of new treatments that either interfere with immune complex binding or receptor organisation. Although these concepts are well established in other fields e.g. growth hormone receptors, very little is known about the organisation of receptors involved directly in immunity. These novel studies will provide us with powerfully useful insights into the first steps in antibody driven tissue destruction.Read moreRead less
Structure And Function Of Receptors For IgG (FcgammaR)
Funder
National Health and Medical Research Council
Funding Amount
$905,280.00
Summary
This reasearch project is attempting to understand one of the most important mechanisms of resistance to infectious disease and one of the most important mechanisms of induction of destructive inflammation in autoimmune disease. These studies will define how blood proteins called antibodies, antibodies bind to the surface of white blood cells via proteins called Fc receptors that activate these white blood cells. Under normal circumstances this system provides resistance to infection but is invo ....This reasearch project is attempting to understand one of the most important mechanisms of resistance to infectious disease and one of the most important mechanisms of induction of destructive inflammation in autoimmune disease. These studies will define how blood proteins called antibodies, antibodies bind to the surface of white blood cells via proteins called Fc receptors that activate these white blood cells. Under normal circumstances this system provides resistance to infection but is involved in some of the most debilitating diseases, including allergies, bleeding disorders called thrombocytopoenias, inflammation of blood vessels, vasculitis, as well as aspects of rheumatoid arthritis. The successful conclusion of this project will result in knowledge that will enable the development of more effective and highly specific therapeutic approaches to the treatment of disease and a better understanding of the functioning of the immune system.Read moreRead less