The Role Of The Transcription Factor IRF4 In Peripheral Cd8 T Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$399,176.00
Summary
T cells protect against viral infections and fight cancer cells. In order to fulfill these roles T cells have to undergo significant phenotypic and functional changes. Our preliminary data indicate a central role for the regulator protein IRF4 in this process, as T cells that lack this protein are unable to grow and acquire the cellular tools necessary to provide protection. We wish to characterize the role of IRF4 in T cells in detail and aim to identify the processes regulated by IRF4.
The Role Of Proteinase Inhibitor 9 In Cytotoxic Lymphocyte Function
Funder
National Health and Medical Research Council
Funding Amount
$820,136.00
Summary
Cytotoxic lymphocytes eliminate virus-infected or cancerous cells from the body. This is achieved by the release of powerful cytotoxins that kill the abnormal cell. Unless carefully targeted these cytotoxins can damage surrounding normal tissue or the cytotoxic lymphocyte itself, and lead to autoimmune disease. One of the most important cytotoxins is a protease called granzyme B. We have discovered a natural inhibitor of granzyme B that is present in cytotoxic cells and testis. Our studies are a ....Cytotoxic lymphocytes eliminate virus-infected or cancerous cells from the body. This is achieved by the release of powerful cytotoxins that kill the abnormal cell. Unless carefully targeted these cytotoxins can damage surrounding normal tissue or the cytotoxic lymphocyte itself, and lead to autoimmune disease. One of the most important cytotoxins is a protease called granzyme B. We have discovered a natural inhibitor of granzyme B that is present in cytotoxic cells and testis. Our studies are aimed at understanding the role of the inhibitor in human immune and reproductive function. We will also design and evaluate synthetic compounds based on the natural inhibitor that will enable us to easily measure granzyme B levels and control its activity.Read moreRead less
Cytolytic Mechanisms Required For Virus Elimination.
Funder
National Health and Medical Research Council
Funding Amount
$698,567.00
Summary
Viruses provoke devastating disease. The immune system kills cells that are infected with viruses. To do this, immune cells release granules that are packaged with different killer molecules. It is unknown which killer molecules participate over the course of an immune response to virus. Here, we will investigate this process for cells that are infected with influenza A virus and herpes simplex virus. This study will allow the design of strategies to limit widespread damage inflicted by viruses.
Regulation Of Leukocyte Lifespan By Granzyme B And PI-9
Funder
National Health and Medical Research Council
Funding Amount
$816,673.00
Summary
To fight infection or cancer the body produces specialized cells called cytotoxic lymphocytes (CLs) which target and eradicate abnormal cells. The number of CLs increases dramatically during infection, and decreases following infection. How this population decrease is controlled is not fully understood, but we propose that a protein used by the CL to kill targets also triggers suicide of the CL after it has destroyed a certain number of targets. How this is achieved is the focus of this project.
The Impact Of Granzyme B On Cytotoxic T Cell Migration Through Tissue
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Cytotoxic T cells (CTL) are white blood cells that move in an orchestrated way into body tissues to target, and destroy, virus-infected or cancer cells. Destruction of these abnormal cells is achieved when they ingest cytotoxic enzymes (proteases) released by CTL. We propose that one of these cytotoxins, granzyme B, has a dual function, and that it is also involved in helping CTL to efficiently move towards the target cells by clearing a path through the local tissue structure.