Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less
Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity ....Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity, insulin resistance and various forms of cancers is well established) are leading to a rapid increase in new cancer cases, thus driving a rapid increase in demand for better treatments. This is particularly relevant in Indigenous health where obesity is on the rise following the transition from a traditional to an urban lifestyle.Read moreRead less
Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. Howeve ....Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. However, DNA vaccines often provide poor protection against infections. This project will explore a unique technology developed in Australia and that will greatly improve the effectiveness of DNA vaccines against a broad range of diseases. Read moreRead less
Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australia ....Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australians.Read moreRead less
Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight i ....Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight into CTL generation by providing greater understanding of how multicellular systems function both at the cellular and molecular level.Read moreRead less
Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur betwee ....Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur between cells of the immune system during infectious diseases. The insight provided by this project will facilitate the design of better vaccines for protection against diseases, including influenza.Read moreRead less
BIOSYNTHESIS OF A FUNGAL TOXIN AND ITS ROLE IN PLANT DISEASE. This project will determine how an important class of toxic molecules, epipolythiodioxopiperazines (EPTs), are made by fungi. Knowledge of the domains and actions of these genes in the biosynthetic pathway may lead to the ability to engineer secondary metabolites with altered specificity, and drugs that alleviate symptoms of secondary fungal toxicoses associated with leukemia, organ transplants and HIV AIDS. Also this project will a ....BIOSYNTHESIS OF A FUNGAL TOXIN AND ITS ROLE IN PLANT DISEASE. This project will determine how an important class of toxic molecules, epipolythiodioxopiperazines (EPTs), are made by fungi. Knowledge of the domains and actions of these genes in the biosynthetic pathway may lead to the ability to engineer secondary metabolites with altered specificity, and drugs that alleviate symptoms of secondary fungal toxicoses associated with leukemia, organ transplants and HIV AIDS. Also this project will also elucidate the role of an EPT, sirodesmin, in blackleg of canola, a disease that costs the Australian canola industry up to $50 million in losses annually. Outcomes of this project may lead to novel blackleg disease control strategies. Read moreRead less
Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifyin ....Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifying how they are formed and how they behave within the body. This work will therefore contribute to the development and production of new-generation vaccines to these so far uncontrollable infectious diseases.Read moreRead less
Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monas ....Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monash University, will permit a rational, structure-based drug discovery platform to be established. The ultimate goal of this innovative and mutlidisciplinary approach, namely a portfolio of phase I therapeutics, will be of substantial benefit in the medical health area.Read moreRead less
Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotec ....Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotechnology company, Cytopia Ltd.Read moreRead less