The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produc ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced in this study will be evaluated for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cel ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced will be assayed for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. The ....Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipa ....Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipates the contribution of innovative tools for molecular biology research, benefiting therapeutic and biotechnology applications. This project will support advanced training of young researchers in frontier technologies, which will expand Australian research capabilities and help produce a higher quality workforce.Read moreRead less
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
Sonification for complex, mission-critical work environments. Human operators must often pay attention to an immediate task while monitoring background information, but intrusive alarms often capture operators' attention inappropriately. We investigate how continuous auditory information ("sonification") can provide low-level background information when all is normal, yet capture attention to abnormalities only when needed. The results of three experiments will determine the most effective combi ....Sonification for complex, mission-critical work environments. Human operators must often pay attention to an immediate task while monitoring background information, but intrusive alarms often capture operators' attention inappropriately. We investigate how continuous auditory information ("sonification") can provide low-level background information when all is normal, yet capture attention to abnormalities only when needed. The results of three experiments will determine the most effective combination of visual and auditory information delivery; how well sonification captures attention when needed; and whether sonification captures attention to deviations from expected changes. Our findings will help establish principles of attentional mapping that significantly extend current approaches to interactive systems design.Read moreRead less
Reducing the harms associated with conscientious objection to abortion. This project aims to critically evaluate the regulation of conscientious objection to abortion. A range of state-based laws regulate this practice in Australia, and there is evidence that all result in inequitable access, harms to women and lack clarity for providers. The project will critically evaluate the legal and regulatory options for managing conscientious objection and interview conscientious objectors to develop a c ....Reducing the harms associated with conscientious objection to abortion. This project aims to critically evaluate the regulation of conscientious objection to abortion. A range of state-based laws regulate this practice in Australia, and there is evidence that all result in inequitable access, harms to women and lack clarity for providers. The project will critically evaluate the legal and regulatory options for managing conscientious objection and interview conscientious objectors to develop a conceptual model to explain their practices. A participatory process with experts will identify the optimal model for regulation and how to translate the model to practice. Expected outcomes are world first evidence on practice, progress towards effective regulation, and benefits will be reduced conflict and harms.Read moreRead less