The initial step of T cell activation of how the external ligand binding is translated to an increase of receptor phosphorylation at the cytoplasmic side is remain poorly understood. It is believed that the loss of immune recognition in cancer and over reactivity in auto-immune diseases are caused by abnormality of this transmembrane signalling transduction. Clarification of this molecular machinery can provide a molecular basis of those diseases and guidelines of more effective therapies.
Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understandi ....Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understanding of histone deacetylases and protein deacetylation in immune cell responses which can be harnessed to manipulate cell functions for basic science and biotechnology uses.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883068
Funder
Australian Research Council
Funding Amount
$150,000.00
Summary
Dako ACIS III Cellular Image Acquisition and Analysis System. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. The ability to visualize and analyze cells and tissues from many different animal species, to elucidate both normal and abnormal functions, will be enhanced by the use of this technology. This will lead to production of quantitative statistical data that in turn will ....Dako ACIS III Cellular Image Acquisition and Analysis System. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. The ability to visualize and analyze cells and tissues from many different animal species, to elucidate both normal and abnormal functions, will be enhanced by the use of this technology. This will lead to production of quantitative statistical data that in turn will inform new approaches to improve and maintain the health of humans and other animals.Read moreRead less
B Cell Survival And Responsiveness In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
I am an immunologist focused on identifying how B lymphocytes, the cells responsible for producing antibodies, survive and participate in immune responses within the body. I achieve this by using specially designed, genetically modified, mice that allow me to follow B lymphocytes within the body and identify their key genetic and external controls. My work is relevant to vaccine development as well as the control of certain autoimmune diseases and B lymphocyte cancers.
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.
Competition For Polarity Influences Lymphocyte Signaling And Function
Funder
National Health and Medical Research Council
Funding Amount
$500,460.00
Summary
Infectious diseases caused by viruses and bacteria remain a significant health problem. CD46 is a protein on the surface of human cells that is used by a number of viruses and bacteria to enter and infect host cells. Through binding to the CD46 protein, viruses and bacteria can induce changes in immune cells, such as T lymphocytes, that affect the way our immune system responds to infection. For example, immunosuppression induced by infection with measles virus is the primary cause of the mortal ....Infectious diseases caused by viruses and bacteria remain a significant health problem. CD46 is a protein on the surface of human cells that is used by a number of viruses and bacteria to enter and infect host cells. Through binding to the CD46 protein, viruses and bacteria can induce changes in immune cells, such as T lymphocytes, that affect the way our immune system responds to infection. For example, immunosuppression induced by infection with measles virus is the primary cause of the mortality and morbidity associated with the disease, and is a phenomenon that is poorly understood. However, there is evidence to suggest that the interaction between measles-infected cells with CD46 on the immune cells is partly responsible for the immunosuppression observed. Our laboratory has recently found that binding of CD46 (by antibody or measles antigen) on immune cells provides a signal to the cell to change its polarisation state (the way proteins are distributed within the cell) and impairs their ability to recognize and kill target cells, and become activated. These observations indicate a new paradigm by which competition of receptor signals for polarization determines signalling outcomes and provides a possible mechanism for how pathogens that bind CD46, such as measles, subvert normal immune cell communication and induce immunosuppression. This proposal aims to investigate the mechanisms behind the effect of polarising signals on immune cells, and will specifically use CD46 and measles virus as a model. The outcomes of this study will define new paradigms in lymphocyte biology and dissect the key pathways that underpin how CD46 influences immune outcome in response to infection.Read moreRead less
Regulation Of The Anti-tumour Immune Response By The Chemokine Decoy Receptor CCX-CKR
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Melanoma is a significant cause of cancer-related deaths in Australians. Death is usually due to metastasis of the cancer to the lungs and other organs. In this project, we will take advantage of unique mouse models to determine whether inhibition of the function of a novel protein can prevent melanoma growth and metastasis to different organs. The results of this study may lead to new therapeutic approaches to control malignant melanoma and other metastatic cancers.