CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.Read moreRead less
Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will gene ....Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will generate significant economic spin-offs to the Australian biotechnology industry and will further relationships and training between research and development.Read moreRead less
Understanding the dynamics of T cell responses to chronic infection. The health, social, and economic impact of chronic infections on the Australian and global populations is enormous. A major obstacle to the development of vaccines against chronic infections is that we have a poor understanding of immune responses to persistent infections. We aim to use bioinformatics and mathematical modelling to understand immune responses to persistent viruses so that we can improve the long-term immune cont ....Understanding the dynamics of T cell responses to chronic infection. The health, social, and economic impact of chronic infections on the Australian and global populations is enormous. A major obstacle to the development of vaccines against chronic infections is that we have a poor understanding of immune responses to persistent infections. We aim to use bioinformatics and mathematical modelling to understand immune responses to persistent viruses so that we can improve the long-term immune control of chronic viral infections such as the human immunodeficiency virus (HIV). This project will strengthen Australian research in the area of interdisciplinary approaches to immunology, which is becoming crucial to interpreting the rapidly increasing volume of data obtained using advanced experimental techniques.Read moreRead less
T cell recognition and control of virus: the balance between T cell receptor diversity and degeneracy. T cells provide an important line of defence in the immune system's resistance against infectious diseases. However, changes to the T cell population during prolonged infection, and with age, can compromise the immune system's ability to fight effectively viral infections. The proposed research will greatly improve our understanding of the recognition and control of viral infections by T cells. ....T cell recognition and control of virus: the balance between T cell receptor diversity and degeneracy. T cells provide an important line of defence in the immune system's resistance against infectious diseases. However, changes to the T cell population during prolonged infection, and with age, can compromise the immune system's ability to fight effectively viral infections. The proposed research will greatly improve our understanding of the recognition and control of viral infections by T cells. The insights gained from this research will enable us to exploit key features of T cell responses to improve the outcome of viral infections in elderly individuals and to develop better vaccines for protection against a range of infectious diseases that affect the Australian population, including HIV and Hepatitis C.Read moreRead less
Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is ....Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is generated in the immune response, and how it becomes narrowed with age or prolonged infection. This information can be used to design vaccines for persistent infections such as HIV, and to improve immune control of infection in the elderly.Read moreRead less
Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow u ....Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow us to develop LipoVax as a new platform technology that can be applied to the development of human vaccines, veterinary vaccines, vaccines for companion animals and vaccines to target infections in feral animals and native wildlife population populations.Read moreRead less
Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and r ....Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and research skill base. Young scientists will be trained in state-of-the-art research techniques in a cross-disciplinary environment that is the way of future biological research. The project may identify potential drug targets for malaria or other infectious diseases. The Intellectual Property will be protected and commercialised.Read moreRead less
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
The effect of age on regulatory T cell control of the innate and adaptive antiviral immune responses. Viral pathogens are a lead cause of infant mortality in the world. This project will define how T regulatory cells limit protective antiviral immune responses in the young. This information is critical for the development of potent antiviral vaccines that are effective from the newborn period without inducing autoimmunity. It will also provide novel insight into the way T regulatory cells can b ....The effect of age on regulatory T cell control of the innate and adaptive antiviral immune responses. Viral pathogens are a lead cause of infant mortality in the world. This project will define how T regulatory cells limit protective antiviral immune responses in the young. This information is critical for the development of potent antiviral vaccines that are effective from the newborn period without inducing autoimmunity. It will also provide novel insight into the way T regulatory cells can be manipulated both to dampen immunity, which can be used to develop strategies to reduce immune mediated disease and limit transplant rejection. Read moreRead less
Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information ab ....Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information about the interaction of this family of viruses, flavivirus with the host.Read moreRead less