Consequences Of Disulfide Exchange In CD4 For Function
Funder
National Health and Medical Research Council
Funding Amount
$332,580.00
Summary
CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells res ....CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells respond to infection and how the HIV virus infects immune cells. Moreover, we have designed a small synthetic compound that blocks the redox chemistry in CD4 and prevents HIV infection in the test tube. We propose to investigate how the redox chemistry in CD4 controls the function of immune cells and infection by HIV.Read moreRead less
Spatial And Temporal Aspects Of Epigenetic Remodelling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$626,707.00
Summary
Epigenetic deregulation occurs commonly in cancer, and can affect not only single genes but can encompass large chromosomal domains, leading to altered expression of oncogenes and tumour suppressor genes, and genomic instability. We will investigate the role of epigenetic remodeling, how spacial reorganisation of the genome, nuclear architecture, chromatin looping and replication timing may affect long range epigenetic deregulation, and ultimately contribute to cancer formation and progression.
How Does Basal Chromatic Structure Predict Cytokine Gene Responses?
Funder
National Health and Medical Research Council
Funding Amount
$521,961.00
Summary
To recognise foreign pathogens and eradicate them from the body, immune cells need to quickly switch on genes encoding factors which communicate between cells and drive the immune response. Incorrect expression of these genes contributes to immune diseases such as asthma, arthritis and leukaemia. The aim of this project is to study how the DNA environment of immune genes controls their ability to be switched on and off, and how altering this environment leads to incorrect gene expression.
An Alternate Function Of The MicroRNA Biogenesis Machinery
Funder
National Health and Medical Research Council
Funding Amount
$302,981.00
Summary
Controlling the activity of genes is crucial. Too much or too little can result in a cell not functioning properly. We have discovered a new way genes are controlled. We have found that an enzyme called Drosha can prevent too much activation of some genes by chopping up the products of these genes. This way of controlling genes appears to be especially important for developmental processes, such as occurs in the embryo. Our goal is to understand this mechanism precisely at the molecular level.
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
Molecular Mechanisms For The Cell-type Specific Regulation Of The Tissue-type Plasminogen Activator Gene
Funder
National Health and Medical Research Council
Funding Amount
$490,500.00
Summary
Tissue-type plasminogen activator (t-PA) is an important enzyme that is widely known for its ability to remove blood clots. More recently, t-PA has been shown to influence memory development and under pathological conditions can promote neuronal cell death. t-PA is produced by many cells including the endothelial cells that line the blood vessels, fibroblasts, as well as cells within the central nervous system. The t-PA gene is regulated very differently in these cell types and this project will ....Tissue-type plasminogen activator (t-PA) is an important enzyme that is widely known for its ability to remove blood clots. More recently, t-PA has been shown to influence memory development and under pathological conditions can promote neuronal cell death. t-PA is produced by many cells including the endothelial cells that line the blood vessels, fibroblasts, as well as cells within the central nervous system. The t-PA gene is regulated very differently in these cell types and this project will address the mechanisms underlying the cell-type specific regulation of the t-PA gene. Endothelial cells, fibroblasts and neuronal cell cultures will be used to study the regulation of t-PA expression. Information gained will not only add to the understanding of the broader field of gene regulation, but may also provide clues to manipulate the expression of the t-PA gene in different cells.Read moreRead less
Role Of NF-kB Recruited SWI/SNF Chromatin Remodeling Complexes In Inducible Gene Expression In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$243,500.00
Summary
The immune system consists of a group of cell types, including T cells, which are capable of recognising foreign agents and eradicating them from the body. T cells are activated by foreign antigen and respond by producing an array of soluble factors including cytokines, which act as communicators between cells. The correct expression of these factors is critical for the maintenance and function of the immune system, and is therefore tightly regulated. The genes encoding these factors are general ....The immune system consists of a group of cell types, including T cells, which are capable of recognising foreign agents and eradicating them from the body. T cells are activated by foreign antigen and respond by producing an array of soluble factors including cytokines, which act as communicators between cells. The correct expression of these factors is critical for the maintenance and function of the immune system, and is therefore tightly regulated. The genes encoding these factors are generally maintained in an 'inactive' state but are switched on rapidly when required. Within the cell, genes or DNA are found wrapped up in a complex protein structure called chromatin which plays an important role in regulating gene expression. Chromatin forms a barrier to active gene expression which must be overcome before the gene can be switched on. There are protein complexes within the cell that are able to alter or remodel chromatin structure from an 'inactive' to an 'active' state. We are investigating one of these chromatin remodeling complexes to determine which genes it is able to switch on and how it targets these particular genes. Aberrant gene expression within T cells contributes to a range of diseases including certain leukemias and inflammatory conditions such as asthma and rheumatoid arthritis. Understanding the events and protein complexes involved in switching on specific genes in T cells will potentially identify molecules which can be targeted in an effort to control inappropriate gene expression in these disease states.Read moreRead less