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
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
A novel role for the proteins Scribble & Dlg in the formation of cell protrusions and their effects on cell function. Dlg and Scribble are recently discovered proteins that are required during development, immune regulation, neural signalling and tumour suppression. Understanding how they work will enable the development of diagnostic and therapeutic tools that have the potential to influence an enormous range of diseases, from cancer to immunodeficiencies and autoimmune diseases. Researchers at ....A novel role for the proteins Scribble & Dlg in the formation of cell protrusions and their effects on cell function. Dlg and Scribble are recently discovered proteins that are required during development, immune regulation, neural signalling and tumour suppression. Understanding how they work will enable the development of diagnostic and therapeutic tools that have the potential to influence an enormous range of diseases, from cancer to immunodeficiencies and autoimmune diseases. Researchers at the PeterMac perform world-leading research into the biology of Scribble and Dlg, and their role in cancer biology and immune function. The mechanistic insight provided by this project will continue that tradition, and facilitate translation of our basic research into clinical applications in important disease areas.Read moreRead less
Investigation of Macrophage Function in an Immunologically Privileged Site. The unique phenotype of the testicular macrophage demands understanding, and this project has the potential to open up an entirely new direction of research. The basic information so generated could facilitate development of strategies to alter either host or donor tissue macrophage functions in order to prevent rejection responses in humans, and be used in the development of new anti-inflammatory drugs. Such technologie ....Investigation of Macrophage Function in an Immunologically Privileged Site. The unique phenotype of the testicular macrophage demands understanding, and this project has the potential to open up an entirely new direction of research. The basic information so generated could facilitate development of strategies to alter either host or donor tissue macrophage functions in order to prevent rejection responses in humans, and be used in the development of new anti-inflammatory drugs. Such technologies will have application in development of novel therapeutics for transplantation and the treatment of chronic inflammatory diseases. Read moreRead less
Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases includ ....Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases including infectious disease, auto-immune disease and leukaemia, and thus a long-term outcome may be improved treatments for such disease. Read moreRead less
Polarity in lymphocytes: Regulation of immune function and cancer. The Fellow will elucidate the mechanisms and consequences of a fundamental new phenomenon in immunology. This is likely to profoundly impact upon approaches to detecting and treating immune-related diseases such as autoimmunity, transplantation, vaccination and immunodeficiencies. The ongoing project and the work that led to our discovery involves interdisciplinary collaborations between physicists and biologists to apply frontie ....Polarity in lymphocytes: Regulation of immune function and cancer. The Fellow will elucidate the mechanisms and consequences of a fundamental new phenomenon in immunology. This is likely to profoundly impact upon approaches to detecting and treating immune-related diseases such as autoimmunity, transplantation, vaccination and immunodeficiencies. The ongoing project and the work that led to our discovery involves interdisciplinary collaborations between physicists and biologists to apply frontier laser technologies to biological studies. These technologies will not only facilitate our elucidation of immune development and function, but will also be made available to other research in Australia and overseas.Read moreRead less
Inside our cells is a complex traffic system. The vehicles are vesicles that come in different shapes and sizes and travel to specific destinations in the cell to deliver cargo such as: surface growth factor receptors that are to have their signalling terminated, proteins and lipids destined for the cell wall for growth or development (like neurite outgrowth) and proteins and hormones destined for secretion (like neurotransmitter release). More than 100 human genetic disorders map to defects in ....Inside our cells is a complex traffic system. The vehicles are vesicles that come in different shapes and sizes and travel to specific destinations in the cell to deliver cargo such as: surface growth factor receptors that are to have their signalling terminated, proteins and lipids destined for the cell wall for growth or development (like neurite outgrowth) and proteins and hormones destined for secretion (like neurotransmitter release). More than 100 human genetic disorders map to defects in one of the components of this system. Proteins called small GTPases provide order for this traffic and allow specific cargo to reach specific destinations. They regulate cell functions by acting as switches, turning biochemical processes on and off inside the cell. Ral is a small GTPase enzyme found in brain and broadly distributed in other cells. We have discovered that Ral is part of a large signalling complex. When activated Ral stimulates effectors, either the exocyst or RalBP1. In turn, mild oxidative stress controls a Ral inhibitor protein called ERp57. The research proposed aims to establish the functional role for the Ral signalling complex in cells. We will determine with which vesicle trafficking events Ral is associated, which effector it utilises in that pathway, and how that effector directs the traffic. We will also map the steps that may lead to inactivation of Ral via ERp57 in cells, and propose that this is mediated by mild oxidative stress. Techniques of molecular biology, biochemistry, molecular biology, proteomics and microscopy will be used to establish these functions. The research will lead to increased knowledge of the significance of this protein to cellular and particularly neuronal cell function. This forms the basis for understanding normal cell function and for identification of further factors causing diseases of vesicle transport. In time, such research aids in the development of specific therapies for sufferers of such diseases.Read moreRead less