T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We h ....T cells are a central component of the immune system and without T cells the body is very vulnerable to infections. One subgroup of T cells is the killer T cells that are important for identifying and killing cells infected by viruses and bacteria. The immune system works to maintain T cell numbers at a fairly constant level and part of this process includes sending signals to the killer T cells from other cells via cell surface protein interactions and soluble mediators, such as cytokines. We have been studying killer T cells, which are missing a protein SOCS1. SOCS1 is important for switching off the signals generated by a group of cytokines. As a consequence of being unable to correctly regulate cytokine signals these killer T cells multiply inappropriately and contribute to disease development. Our current work is aimed at achieving a better understanding of the particular interactions between killer T cells and other immune system cells and the soluble factors that deliver important signals for maintaining killer T cells in the immune system. The ability to better understand the factors controlling the maintenance of killer T cells will enable us to more intelligently target the immune system ,which is important for improving vaccine strategies and cancer immunotherapy as well as for controlling T cells that are activated inappropriately, such as in autoimmune disease.Read moreRead less
My research centers on the formation and function of T cells, with particular emphasis on normal T cell homeostasis and how T cells respond to foreign antigens while tolerating self antigens.
A Novel Mechanism For The Regulation Of T Cell Shape And Function.
Funder
National Health and Medical Research Council
Funding Amount
$384,398.00
Summary
T cells are a key component of the immune system, and an understanding of their regulation has already lead to important therapeutic interventions. It is now apparent that the shape of the T cell impacts upon its ability to be activated, to migrate through the body, and to kill target cells. We have identified a novel means by which T cell shape is controlled, involving a group of proteins which orchestrate molecular traffic throughout the cell. This project application is to elucidate the mecha ....T cells are a key component of the immune system, and an understanding of their regulation has already lead to important therapeutic interventions. It is now apparent that the shape of the T cell impacts upon its ability to be activated, to migrate through the body, and to kill target cells. We have identified a novel means by which T cell shape is controlled, involving a group of proteins which orchestrate molecular traffic throughout the cell. This project application is to elucidate the mechanisms by which the group of proteins regulates T cell shape and function. We will test whether the proteins act together to integrate signals throughout the entire T cell, and will test whether the proteins influence T cell function in the test tube and in the mouse.Read moreRead less
The Role Of Epigenetic And Transcriptional Regulation In CD8+ T Cell Effector Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$72,571.00
Summary
All cells contain DNA that is tightly wrapped around proteins, whereby changes in the structure allow for the expression of proteins. Cells of the immune system express proteins that can resolve viral infections. This study plans to examine the factors mediating the changes in DNA that allow for the expression of these proteins in immune cells. Insights will enable a greater understanding of how these proteins are generated and maintained, and hence will have implications for vaccine design.
Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. The ....Autoimmune diseases constitute a significant medical problem in the developed world and are increasing in incidence. Many control mechanisms exist in the body, but in people with genetic susceptibility to autoimmune disease, the mechanisms fail and the body's immune system attacks normal tissues or organs. We have developed a new approach, using the cells which train the immune system, to re-educate the cells that would otherwise attack normal healthy tissues in autoimmune-prone individuals. These cells (dendritic cells) are genetically modified to express the molecular targets of the autoimmune response. This in turn switches off the response to these targets. In this project, we will explore how these cells can be used to turn off the harmful cells present in the immune system.Read moreRead less
Transcriptional Regulation And The Role Of Key Histone Variants In Defining Gene-specific Chromatin States.
Funder
National Health and Medical Research Council
Funding Amount
$450,696.00
Summary
One of the most outstanding and significant questions within this genome era has been to unravel how chromatin structure within the nucleus of a cell is capable of regulating the complex expression patterns needed for cell proliferation, cell differentiation and cellular responses to environmental factors such as pathogens and signaling molecules. Studies on lower eukaryotes have demonstrated that deposition of histone variants provides a powerful mechanism for modulating chromatin structure. To ....One of the most outstanding and significant questions within this genome era has been to unravel how chromatin structure within the nucleus of a cell is capable of regulating the complex expression patterns needed for cell proliferation, cell differentiation and cellular responses to environmental factors such as pathogens and signaling molecules. Studies on lower eukaryotes have demonstrated that deposition of histone variants provides a powerful mechanism for modulating chromatin structure. To date, there is no comprehensive picture of the contribution of histone variants in the transcriptional process in higher eukaryotes. Preliminary results obtained in our laboratory have provided fascinating first insights into the role of key histone variants in the control of regulatory regions of key genes involved in the immune system. Importantly, these results have enabled us to identify a novel chromatin regulatory mechanism that this proposal aims to investigate in necessary detail. The outcome of the proposed research will give an in depth understanding on how chromatin structure is influenced by the recruitment of histone variants and how this mechanism is crucially involved in gene regulation. Crucially, we will attempt to answer some of the most outstanding and significant questions about how chromatin dynamics within the nucleus switch on-off a defined subset of genes in response to a particular environmental stimulus. In addition, the new level of understanding of the events in metastasis-invasion will help provide advances in cancer and gene therapy.Read moreRead less
Chromatin Remodelling And Transcriptional Regulation Of CD8 T Cell Effector Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
A major role for cytotoxic, or killer, T cells is the recognition and removal of virus infected or tumor cells from a host. Upon recognition of a target host cell, killer T cells deliver a package of proteins, termed granzymes, that mediate the removal of these virus infected and tumor cells. Naive killer T cells need to be activated to start producing these effector molecules. This proposal plans to examine the factors that regulate both induction and maintanence of cell specific expression of ....A major role for cytotoxic, or killer, T cells is the recognition and removal of virus infected or tumor cells from a host. Upon recognition of a target host cell, killer T cells deliver a package of proteins, termed granzymes, that mediate the removal of these virus infected and tumor cells. Naive killer T cells need to be activated to start producing these effector molecules. This proposal plans to examine the factors that regulate both induction and maintanence of cell specific expression of these effector molecules. We plan to identify the molecular events that occur within a cells genome to turn on granzyme gene expression and how these factors influence subsequent killer T cell function. The conclusions from these studies will enable us to determine why some killer T cell responses are not effective and what can be done to improve killer T cell function. This has implications for the development of novel vaccine strategies designed to induce immunity against both viral and tumour challenges.Read moreRead less