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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
Multifunctional biodegradable nanoparticles for enhanced DNA vaccine delivery. DNA vaccine, which shows better immunological and economic merits than conventional vaccines, suffers clinical failure due to the difficulty of delivering intact DNA molecules to relevant cells. This project seeks to develop smart polymer nanospheres to protect the DNA molecules from premature degradation in order to improve its efficacy.
A novel link between metabolism and host defence. This project aims to delineate how a protein modification that consists of the addition of a small sugar to cellular proteins, known as O-GlcNAcylation, provides a link between metabolism and complex cell functions. The model for these studies is a cell type of the immune system known as dendritic cells. Upon encountering pathogens these cells undergo metabolic changes that increase the rate of O-GlcNAcylation of proteins involved in immune respo ....A novel link between metabolism and host defence. This project aims to delineate how a protein modification that consists of the addition of a small sugar to cellular proteins, known as O-GlcNAcylation, provides a link between metabolism and complex cell functions. The model for these studies is a cell type of the immune system known as dendritic cells. Upon encountering pathogens these cells undergo metabolic changes that increase the rate of O-GlcNAcylation of proteins involved in immune responses, altering their function. This project will study how O-GlcNAcylation works and is regulated. The project expects to develop new technology and provide high-level training, increasing the competitiveness of the strategic biotechnology sector in AustraliaRead moreRead less
Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices w ....Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices will be designed with precision and function to meet the delivery needs in vivo. These polymer structures will be suitable for use in drug and gene delivery providing Australian products with advanced features and capabilities, significantly improving product performance.Read moreRead less
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restricti ....Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restriction). T lymphocytes that can recognise antigens in the absence of MHC or MHC like molecules challenges a major paradigm in the field of immunology. As T cell based therapy underpins treatments for cancer and infection, new mechanisms of T cell activation that are independent of patient genotype should ultimately create opportunities for therapeutic and commercial development, leading to both health and economic benefits.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
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
A structural and functional investigation into events within the immunological synapse. This project will provide fundamental insight into processes that control infection. Investigating processes central to immunity is important, as it will further the understanding of these critically-important events. Such knowledge will increase Australia's research standing, as well as having the potential to generate novel therapies
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