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
Activation mechanisms of store-operated calcium channels in liver cells. Currently, one of the most active areas of research in biology involves the molecular mechanisms that control the activity of cells. Defining these will provide a deeper understanding of normal function and disease, and provide potential therapeutic targets. This group has an international reputation for its work and it makes a major input to maintaining Australia as a significant contributor to this field. While its resea ....Activation mechanisms of store-operated calcium channels in liver cells. Currently, one of the most active areas of research in biology involves the molecular mechanisms that control the activity of cells. Defining these will provide a deeper understanding of normal function and disease, and provide potential therapeutic targets. This group has an international reputation for its work and it makes a major input to maintaining Australia as a significant contributor to this field. While its research has broad application in biology, its specific focus, calcium signalling in the liver, will provide the basis for understanding liver function and disease and, potentially, for developing new treatments for liver disease associated with abnormal calcium homeostasis.Read moreRead less
High Resolution EM Tomography of Specialised Plasma Membrane Domains. This project will provide National benefits in two major areas. Firstly, these studies will greatly increase our understanding of the cellular structures which are crucial to the functioning of cells in the body. Understanding the structure of the components of animal cells in three dimensions will provide long-term benefits in the quest to understand how a cell works in health and what goes wrong in disease. Secondly, this pr ....High Resolution EM Tomography of Specialised Plasma Membrane Domains. This project will provide National benefits in two major areas. Firstly, these studies will greatly increase our understanding of the cellular structures which are crucial to the functioning of cells in the body. Understanding the structure of the components of animal cells in three dimensions will provide long-term benefits in the quest to understand how a cell works in health and what goes wrong in disease. Secondly, this project will allow us to develop the new method of electron microscope tomography and apply it to a crucial question in biology. This will be a vital technique for Australian investigators in the coming years and this project will allow scientists and students to be trained in these state-of-the-art techniques.Read moreRead less
Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens ....Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens of which account for billions of dollars and millions of Australians. This project aims to understand one of the major mechanisms that controls cell migration, which is expected to produce significant economic and social outcomes in the areas of basic science knowledge, human health, and biotechnology. Read moreRead less
Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of ele ....Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of electrophysiology and molecular biology we expect to learn the fundamental mechanisms that modulate the opening and closing of store-operated calcium channels and to gain an important information that can be used for determining the molecular structure of these channelsRead moreRead less
Calcium signalling in neurons of the central nervous system. Understanding of the processes of cell-to-cell communication between neurons that comprise the brain and central nervous system is of primary importance to our understanding of fundamental phenomena such as voluntary and reflex movement, sensory responses and learning and memory. We would like to obtain a better understanding of how calcium controls neuronal and synaptic function. These studies will combine high-speed fluorescence ima ....Calcium signalling in neurons of the central nervous system. Understanding of the processes of cell-to-cell communication between neurons that comprise the brain and central nervous system is of primary importance to our understanding of fundamental phenomena such as voluntary and reflex movement, sensory responses and learning and memory. We would like to obtain a better understanding of how calcium controls neuronal and synaptic function. These studies will combine high-speed fluorescence imaging, electrophysiological recording, gene transfer using Adeno- and Sindbis viruses, and genetically designed and targeted biosensors to describe key "descriptors" of the calcium signals generated as neurons of the central nervous system ?talk? to each other.Read moreRead less
Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also disco ....Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also discovered that this cross-talk between prostaglandin- and cytokine-receptor signalling pathways occurs in preadipocyte and breast cell lines and propose that this research will serve as a paradigm for understanding how sensitivity to cytokines can be controlled at a molecular level.Read moreRead less