Population Genomics Of Plasmodium Falciparum Surface Antigen Genes
Funder
National Health and Medical Research Council
Funding Amount
$385,319.00
Summary
Like most other organisms, each malaria parasite has unique characteristics. A malaria vaccine will need to incorporate these differences to be effective against all parasites in a population. This project will measure the variability and fluctuations of eight of the most promising vaccine targets in a number of natural malaria populations. With this knowledge, a vaccine that is effective against all parasites in the population can be developed and its future success maintained.
Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to th ....Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to the immune system. We have already identified some proteins that are expressed on the surface of only one type of dendritic cell. We will explore the possible use of these proteins as a means of delivering a vaccine to only one type of dendritic cell. This project will also identify new genes that are expressed in some types of dendritic cells but not others. These new genes whose expression does differ amongst the dendritic cells are potential targets for manipulating the immune system and ensuring more efficient vaccination.Read moreRead less
Molecular Interactions Of The Tetraspanins CD37, TSSC6 And CD151 In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$566,575.00
Summary
The tetraspanins are a new type of protein that are found at the surface of cells. Cells of the immune system, such as white blood cells, display at their surface, up to 20 different tetraspanin proteins. However, the precise contributions of these tetraspanin proteins to immunity is still not clear, nor is it clear exactly how tetraspanin proteins differ from one another and why white blood cells need to display so many different tetraspanins. Using genetic technology we have created mice which ....The tetraspanins are a new type of protein that are found at the surface of cells. Cells of the immune system, such as white blood cells, display at their surface, up to 20 different tetraspanin proteins. However, the precise contributions of these tetraspanin proteins to immunity is still not clear, nor is it clear exactly how tetraspanin proteins differ from one another and why white blood cells need to display so many different tetraspanins. Using genetic technology we have created mice which are unable to express certain individual tetraspanin proteins at their cell surface. Excitingly, the immune systems of these mice are not normal, in particular one type of white blood cell, the T cell responds in an exaggerated manner to stimulation. These results suggest a role for tetraspanins in the control and regulation of the immune system. This project will extend these results and work out the precise molecular mechanism by which the tetraspanins exert this control. In the future, a full understanding of how tetraspanins control T cells may ultimately lead to novel ways of controlling the immune system.Read moreRead less
Receptors And Ligands Regulating Human NK Cell Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$692,040.00
Summary
A white blood cell called a Natural Killer (NK) cell is critical in the early control of viral infections and cancer. NK cells kill the diseased cells and secrete immunological hormones (cytokines) that alter how cells of the blood and immune systems respond. These functions of NK cells are markedly increased when NK cells are stimulated to divide. This project seeks to understand how NK cell proliferation is controlled. Receptors that recognise 'self' inhibit NK cell function and cell division ....A white blood cell called a Natural Killer (NK) cell is critical in the early control of viral infections and cancer. NK cells kill the diseased cells and secrete immunological hormones (cytokines) that alter how cells of the blood and immune systems respond. These functions of NK cells are markedly increased when NK cells are stimulated to divide. This project seeks to understand how NK cell proliferation is controlled. Receptors that recognise 'self' inhibit NK cell function and cell division thereby preserving self and destroying diseased cells. Yet many NK cells express both an inhibitory and activating receptor for this same 'self' protein. We will investigate what determines the outcome of this competing information. Many NK cell receptors remain to be identified and we will use a gene expression approach and monoclonal antibodies to identify these and determine how they affect NK cell proliferation. We will use molecular engineering to construct multimeric arrays of new NK cell receptors to search for the ligand molecules that they interact with on other cells. Identifying NK cell receptors and their ligands regulating NK cell proliferation and function will enable us to understand the role of these cells in health and in inflammatory diseases and cancer.Read moreRead less
Expression And Role Of Integrins During Lens Development And Cataractogenesis
Funder
National Health and Medical Research Council
Funding Amount
$336,760.00
Summary
Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous rese ....Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous research, which has identified molecules (growth factors) that are involved in either the regulation of normal lens development and growth (FGF and TGF-beta) or the induction of cataractous changes in the lens epithelium (TGF-beta). The studies are directed at identifying members of an important family of cell adhesion molecules, the integrins, in the lens and examining the role that these molecules play in controlling lens structure and function. These cell surface glycoproteins function in adhesion of cells to each other and to extracellular matrix, and transmit signals in response to changes in the extracellular environment. Such responses include cell proliferation, migration and differentiation. In this regard they often act in concert with growth factor receptors (eg. FGF and TGF-beta). After defining where and when integrins are expressed in the developing lens we will investigate their function in mediating various lens cell responses by using genetic manipulations to alter the expression of integrins or their intracellular signaling mediators in lenses of transgenic mice. In addition, a lens explant culture system will be used to investigate the roles integrins play during lens development and during formation of anterior subcapsular cataract by TGF-beta. These studies will provide important insights into the molecular mechanisms that control cellular events in normal and abnormal lens development.Read moreRead less
The Role Of The Dendritic Cell Surface Molecule Clec9A In Dendritic Cell Subset Function And Dead Cell Recognition
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Dendritic cells (DC) are sentinels of the immune system. DC monitor the environment and regulate tolerance to self versus immunity to dangerous material. Different types of DC perform different jobs. We have identified a new surface molecule, Clec9A, on some mouse and human DC. We will investigate the function of Clec9A in the immune response. We will also use Clec9A to help unite mouse and human DC biology, since until now there have been few useful marker molecules common to both species.
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