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
The Role Of Vif In Enhancing HIV Replication And Effecting The Integrity Of The Replication Complexes Of HIV
Funder
National Health and Medical Research Council
Funding Amount
$260,200.00
Summary
HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral l ....HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral life cycle. We aim to investigate the action of Vif in stabilizing early HIV reverse transcription complexes to understand how it acts to enhance HIV replication and viral infection. The early stages of HIV replication are critical for establishing infection and hence ideal targets for therapeutic intervention. This research will help understand how Vif works in a cell and affects the infectivity of HIV viral particles and may be suggestive of potential targets for development of anti-viral drugs.Read moreRead less
THE CMRF-35 FAMILY OF MOLECULES: GENE STRUCTURE, EXPRESSION AND FUNCTION
Funder
National Health and Medical Research Council
Funding Amount
$367,669.00
Summary
White blood cells are the army which fights invasion by foreign organisms or cancer cells. Their main artillery and communication systems are located on the cell surface as protein molecules. These recognize foreign material and danger signals, and signal into the cell to direct interactions with other cells- soluble molecules in the immune system. We have discovered a new group of molecules called the CMRF-35 family which are found on the surface of different white blood cells. We have characte ....White blood cells are the army which fights invasion by foreign organisms or cancer cells. Their main artillery and communication systems are located on the cell surface as protein molecules. These recognize foreign material and danger signals, and signal into the cell to direct interactions with other cells- soluble molecules in the immune system. We have discovered a new group of molecules called the CMRF-35 family which are found on the surface of different white blood cells. We have characterized two members of the CMRF-35 family by studying the structure of their genes and the cells which express them. These studies will determine if the known CMRF-35 molecules are able to send signals from the cell surface into the cell to activate or inhibit a functional response by cells that express them. We hope to identify the triggers that initiate a signal from CMRF-35 molecules into the cell and whether there are molecules which bind CMRF-35 molecules and then get moved from the surface to inside the cell. Our data suggests that there are other unknown members of this family. We will determine how many members there are in this family by studying the DNA of genes that are related to the known CMRF-35 molecules. This will allow us to charactertize novel molecules that may be important for white cell function. Discovering new white cell surface molecules and determining their function increases our understanding of how the immune response works. If these CMRF-35 molecules represent a large family, it is highly likely that they have important roles in the immune response. By understanding the signals these molecules send to the cell nucleus we may be able to exploit their function to fight disease. For example where the immune system has not recognized cancer cells as dangerous, we might use the activating CMRF-35 molecules to stimulate a response. In the case of auto-immunity we may be able to reduce the responses via inhibitory CMRF-35 molecules.Read moreRead less
The Molecular Basis To The Development And Function Of The Thymic Microenvironment.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The ability of the body to defend itself against infection is dependent on white cells in the blood called T lymphocytes, so-named because they are produced in the thymus gland. In the absence of these T cells, there is severe immunodeficiency. On other hand if the T cells are hyperactive, they can confuse their role and destroy normal tissues (autoimmunity). Imbalances in the types of T cells can also predispose patients to allergies and failures in responses to tumours. This project seeks to i ....The ability of the body to defend itself against infection is dependent on white cells in the blood called T lymphocytes, so-named because they are produced in the thymus gland. In the absence of these T cells, there is severe immunodeficiency. On other hand if the T cells are hyperactive, they can confuse their role and destroy normal tissues (autoimmunity). Imbalances in the types of T cells can also predispose patients to allergies and failures in responses to tumours. This project seeks to identify the genes required to create T cells in the thymus. Specifically it addresses the structural cells of the thymus which provide the unique environment for converting bone marrow precursors exclusively into T lymphocytes. Understanding the genetic and thus molecular basis to this will be very important biologically but may also provide more sophisticated stratgies for treating diseases on T cell origin.Read moreRead less