The Cellular And Molecular Basis To The Paradox Of Positive Versus Negative T Cell Selection
Funder
National Health and Medical Research Council
Funding Amount
$278,090.00
Summary
The protection against disease requires the generation of white blood cells called T lymphocytes that are produced in the thymus. Each T cell has a specific surface receptor, generated by random gene switching, that can react against foreign pathogens. Since there is a very high conservation of molecules used in all organisms, some of these receptors could by chance also react against normal cells in the host. Eliminating all such self-reactive cells would mean, however, the repertoire remaining ....The protection against disease requires the generation of white blood cells called T lymphocytes that are produced in the thymus. Each T cell has a specific surface receptor, generated by random gene switching, that can react against foreign pathogens. Since there is a very high conservation of molecules used in all organisms, some of these receptors could by chance also react against normal cells in the host. Eliminating all such self-reactive cells would mean, however, the repertoire remaining for eliminating infection would be too low and immunodeficiency develops. This project investigates the mechanisms controlling the balance between defence infection and the need to prevent immune-based self destruction termed autoimmunity.Read moreRead less
The Generation, Fate And Functional Potential Of Recent Thymic Emigrants
Funder
National Health and Medical Research Council
Funding Amount
$318,856.00
Summary
A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called auto ....A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called autoimmunity. Since these developing T lymphocytes will not see all kinds of self tissue while in the thymus, we propose that their education to prevent self-tissue reactivity may continue for some time after they leave the thymus.Read moreRead less
DETERMINING THE ROLE OF ER STRESS INDUCED APOPTOSIS IN THYMIC NEGATIVE SELECTION
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
Apoptosis is an evolutionarily conserved mechanism for killing unwanted cells that are no longer needed, damaged, infected with pathogens or dangerous. Defects in apoptosis can cause a number of diseases. For example, abnormal survival of cells can cause cancer or autoimmune disease. Bim is a protein that induces apoptosis and act as a barrier against cancer and autoimmune diseases. This work is aimed at understanding how Bim acts as a barrier against the development of autoimmunity.
The establishment of an immune system that is able to distinguish between self and non-self is of fundamental importance for good health and survival. How this specificity is achieved has been an area of intense investigation for many years because a breakdown of this process leads to the development of autoimmune diseases, such as diabetes, or an inability to fight pathogenic organisms. It has been known for many years that the development T cells, a subset of cells involved in mounting immune ....The establishment of an immune system that is able to distinguish between self and non-self is of fundamental importance for good health and survival. How this specificity is achieved has been an area of intense investigation for many years because a breakdown of this process leads to the development of autoimmune diseases, such as diabetes, or an inability to fight pathogenic organisms. It has been known for many years that the development T cells, a subset of cells involved in mounting immune responses, occurs in the thymus. The thymus produces large numbers of immature T cells (called thymocytes) from which a small number receive the appropriate signals to survive and develop into mature T cells. These tailor-made T cells can then enter the blood and peripheral lymphoid organs where they fight infectious organisms without reacting against host (i.e. self) tissues. The work for this project is aimed at determining how proteins inside thymocytes transmit signals that determine whether thymocytes either survive, and develop into T cells, or are eliminated because they react too strongly with self proteins. We have established that a protein called c-Cbl is central to this process as it regulates the initial strength of the signal that determines the fate of thymocytes. Our aim is to identify the putative key protein regulated by c-Cbl that can sense when a signal is too strong following the binding of a thymocyte to a self protein and directs a cell death signalling response. From this critical point of signal splitting we also aim to identify proteins that relay the death signal to the nucleus where they trigger the production of well-characterised proteins required to mediate cell death. By identifying the proteins in this signalling pathway we will have a greater capacity to control the magnitude of immune responses and therefore be able to lessen tissue damage caused by autoimmune reactions.Read moreRead less
Germinal Centres, Rogue B Cells And The Genesis Of Immunological Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$753,300.00
Summary
This study will determine how the immune system is normally prevented from producing autoantibodies that target the body's own cells and how this fails in autoimmune diseases such as lupus. Targeted studies of a newly discovered "rogue" white blood cell will also provide new clues on how autoimmune diseases arise. In addition, modeling of human immunological disease in mice via CRISPR/Cas9 mutagenesis will provide valuable new insights into their causes and potential treatments.
Positive And Negative Selection In The Germinal Centre Reaction
Funder
National Health and Medical Research Council
Funding Amount
$1,289,965.00
Summary
We will investigate the processes that control the production of antibodies by the immune system. In particular, we will determine how the immune system is normally prevented from producing autoantibodies that target the body's own cells and how this fails in the case of autoimmune diseases such as lupus. Targeted studies of a new type of "rogue" white blood cell we have identified will also provide important clues on how autoantibody-producing cells escape and cause autoimmune disease.
I am an Immunologist interested in the role of B-lymphocytes, their survival and expression of a novel chemoreceptor in Autoimmunity. I also study the important role of Neuropeptide Y in modulating key immune functions.
Long Term Outcome From Early Childhood Brain Injury: 10 Year Follow Up
Funder
National Health and Medical Research Council
Funding Amount
$338,900.00
Summary
The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally he ....The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally held view that children are resilient and recover fully from early brain insult. Rather, we have shown that, up to 5 years post-TBI, many children experience impairments in physical, cognitive and behavioural function. These impairments result in educational, vocational, social and emotional problems, limiting the child's capacity to meet developmental expectations and achieve adequate quality of life. The implication is that these problems will lead to life-long disability, resulting in high levels of individual, family and community burden. However, with follow-up data limited to 5 years, there remains a possibility that ongoing developmental processes may support an extended recovery period in childhood TBI, in comparison to the 2-year period cited in adult models. The review of this sample, 10 years post-injury, provides an unprecedented opportunity to address this possibility and to document recovery-outcome as children move into adolescence and adulthood. Not all children experience problems post-injury. However, predicting individual outcome remains a significant challenge, with particular clinical relevance to treatment and follow-up. Thus, the second aim of the proposed study is to examine factors that contribute to recovery and outcome.Read moreRead less
Indigenous Community Action To Reduce Harms Associated With Heavy Cannabis Use In Cape York
Funder
National Health and Medical Research Council
Funding Amount
$814,163.00
Summary
Cape York Indigenous communities together with Queensland Police, are working to reduce cannabis availability. Community leaders report that cannabis use is widespread in their communities with associated problems such as violence, mental illness and economic hardship. This project will deliver tailored strategies to reduce the demand for cannabis whilst providing support and education about the effects of cannabis and reasons to avoid using it over a three year period.