Functional Aspects Of CD52 Signalling In Immune Regulation
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Autoimmune disease, such as Rheumatoid arthritis, Type 1-Diabetes, Lupus and Multiple Sclerosis, is caused by disruptions in the normal control of the immune system. A type of cell called a regulatory T-cell can prevent these damaging immune reactions. However, we do not know how T-cells do this. CD52 is a protein found on the surface of T-cells. Our preliminary work shows that CD52 also suppresses these damaging immune responses. This project researches how CD52 influences the immune system.
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
Understanding The Role Of Innate Immune Cells In Regulating Gut-associated Lymphoid Tissues At Steady-state And In Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immuno ....The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immunotherapeutics.Read moreRead less
Understanding the immune response is proving extremely complex and promising results for disease treatments from animal models are often difficult to translate to new clinical therapies. My research is unearthing weaknesses in our current knowledge of the immune system and seeking to replace them with a foundation that can exploit new developments in computer modelling and systems biology. In this way I aim to rationally manipulate the immune response.
Molecular And Functional Charcterization Of A Novel Population Of Foxp3+ Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,274.00
Summary
Regulatory T cells (Tregs) are essential for the prevention of autoimmunity and death. We have identified a new population of effector or ïactiveÍ Tregs, and identified some of the proteins that are required for these cells to function. We now aim to examine the development of these cells in detail, illuminate their precise function, their distribution and mode of action. This has potentially huge implications in treatment and diagnosis of autoimmunity, cancer or transplantation.
Dissecting In Vivo Cellular Responses To Interferons In Pathogen-infected Hosts
Funder
National Health and Medical Research Council
Funding Amount
$479,694.00
Summary
Tuberculosis (TB) is caused by virulent bacterium Mycobacterium tuberculosis and is a leading cause of death worldwide. Mechanisms underlying host resistance to the pathogen are poorly understood. Using a novel reporter mouse, the function of interferons in Mtb infection will be defined in vivo by tracking the cytokine-responsive cells. This will increase our understanding of the effects of these important cytokines in vivo, and could provide new candidate biomarkers for TB diagnosis.