Costimulation In Progressive Non-immune Tubulointerstitial Renal Disease.
Funder
National Health and Medical Research Council
Funding Amount
$434,875.00
Summary
Current treatments for chronic kidney disease are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason and many more die of kidney failure or its complications. This project will examine the role of costimulatory molecules in causing chronic kidney disease (CRD) to progress and their potential as targets for specific ....Current treatments for chronic kidney disease are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason and many more die of kidney failure or its complications. This project will examine the role of costimulatory molecules in causing chronic kidney disease (CRD) to progress and their potential as targets for specific therapy to slow the progression of CRD. In chronic kidney diseases of all types, the kidney becomes infiltrated with inflammatory cells. The amount of inflammation has an important bearing on the severity of kidney failure and the rate at which kidney disease progresses. There are a range of different cells that invade the inflamed kidney, some may worsen disease while some may protect against it. Current treatments are non-selective and may, by suppressing inflammation, prevent both repair and protection. Costimulatory molecules have been shown to be important in the regulation of inflammatory cell activation in transplantation and some autoimmune diseases. We, and others, have evidence to suggest that costimulatory molecules may be pivotal to the development and progression of kidney inflammation in CRD as well. This project will use two robust animal models of human CRD to define the role of costimulatory molecules in progression of kidney disease. If, as our preliminary evidence suggests, costimulatory molecules are shown to alter disease progression, then they will provide excellent targets for new treatments. Eventually, treatment directed against costimulatory molecules may be used as more effective and safer therapy for human kidney disease.Read moreRead less
Co-administration Of DNA Encoding Co-stimulatory Molecules Enhances The Efficacy Of Immune Response To Foreign Antigen
Funder
National Health and Medical Research Council
Funding Amount
$182,000.00
Summary
Vaccines to prevent or treat infectious diseases and some cancers are urgently needed. Infected cells and some cancer cells display unique proteins which the body's immune system can recognises as 'foreign'. The body will then mount an immune response, which, if successful, will eradicate the infected or cancerous cells. Dendritic cells (DCs) initiate the body's immune response by instructing other immune cells to mount a response. For a vaccine to be successful it is important that the vaccine ....Vaccines to prevent or treat infectious diseases and some cancers are urgently needed. Infected cells and some cancer cells display unique proteins which the body's immune system can recognises as 'foreign'. The body will then mount an immune response, which, if successful, will eradicate the infected or cancerous cells. Dendritic cells (DCs) initiate the body's immune response by instructing other immune cells to mount a response. For a vaccine to be successful it is important that the vaccine activates the DCs in the right way. We propose to activate DCs by vaccinating with DNA encoding recently identified costimulatory molecules, as well as DNA encoding the foreign antigen. Our earlier work leads us to believe that this will enhance the immune response, and lead to a more effective state of immunityRead moreRead less
Inhibition Of Endothelial Cell Adhesion Molecule Expression By High Density Lipoproteins
Funder
National Health and Medical Research Council
Funding Amount
$80,550.00
Summary
It is well known that high levels of cholesterol in blood cause coronary heart disease. However, it is also known that not all of the blood cholesterol is bad. If it is carried in particles called low density lipoproteins or LDLs it causes heart disease. But if it is carried in other particles known as high density lipoproteins or HDLs it does not. In fact, it is now well known that HDLs actually protect against the development of coronary heart disease. There are two main actions of HDLs that c ....It is well known that high levels of cholesterol in blood cause coronary heart disease. However, it is also known that not all of the blood cholesterol is bad. If it is carried in particles called low density lipoproteins or LDLs it causes heart disease. But if it is carried in other particles known as high density lipoproteins or HDLs it does not. In fact, it is now well known that HDLs actually protect against the development of coronary heart disease. There are two main actions of HDLs that contribute to their ability to protect. Firstly, they are known to drain cholesterol out of coronary arteries. We have recently shown that they have a second action. The end result of this second action is a slowing down of the entry into coronary arteries of cells called monocytes that are necessary for the development of the atherosclerosis that causes the heart disease. This project is concerned with this ability of HDLs to slow down the development of atherosclerosis by the second action. We have found that this second action of HDLs is influenced by the type of fats they carry. We propose now to investigate the mechanism by which different fats influence this action of HDLs with a view to devising new strategies for the prevention of heart disease.Read moreRead less
Structural Biology Of Malaria Parasite Invasion And Antibodies-mediated Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$1,562,250.00
Summary
Malaria results in significant mortality but an effective vaccine does not yet exist. The Rh5-CyRPA-Ripr complex is essential for malaria parasite to invade erythrocytes and is the leading vaccine candidate. We aim to visualise the atomic details of the Rh5-CyRPA-Ripr complex during parasite invasion of erythrocytes and how antibodies neutralise this key protein complex. This information will advance knowledge on malaria parasite invasion, which will help to design an effective malaria vaccine.