Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysica ....Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysical binding assays to characterise compounds that are produced on small scale using parallel chemistry. This approach will enable better chemical probes to be developed more rapidly at lower cost than is currently possible.Read moreRead less
Glycan-based prebiotic approaches to increase food safety in Australia. Since the launch of the first Australian Animal Sector National Antimicrobial Resistance Plan (2018) several approaches have been suggested to reduce the use antibiotics in agriculture, however no alternatives to antibiotics have been suggested or trialled. In this proposal we aim to develop a novel glycan-based prebiotic strategy to reduce Campylobacter jejuni colonisation in chicken and poultry by disrupting important glyc ....Glycan-based prebiotic approaches to increase food safety in Australia. Since the launch of the first Australian Animal Sector National Antimicrobial Resistance Plan (2018) several approaches have been suggested to reduce the use antibiotics in agriculture, however no alternatives to antibiotics have been suggested or trialled. In this proposal we aim to develop a novel glycan-based prebiotic strategy to reduce Campylobacter jejuni colonisation in chicken and poultry by disrupting important glycan-glycan interactions. Outcomes of this proposal is a cost-effective antibiotic- and vaccine-independent animal feed supplement strategy that will decrease the risk of human food-borne illness and therefore promoting food safety and public health in Australia. Read moreRead less
BioPPSy: An open source BIOchemical Property Prediction SYstem. Computer software will be developed for the prediction of the pharmacokinetic properties of small molecules to assist in the development of new compounds with drug-like properties. The software will be made freely available to promote its use and further development.
Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: sy ....Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: synthesise novel heteroarylalkylamines distinct from bedaquiline and designed to be more polar, less basic, and metabolically more stable; and, test all successfully synthesised target compounds for mechanism-based anti-tuberculosis activity, hERG-mediated cardiotoxicity, metabolic instability, and phospholipidosis.Read moreRead less
Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet ....Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet poorly understood issue in mitochondrial genomics and evolutionary biology. Knowledge from this project will also improve our understanding of other important issues that are associated with animal mitochondria; like the mechanisms of mitochondrial disease and ageing, and the evolution of modern humans and other animals.Read moreRead less
New models for the role of chromatin in controlling inducible gene expression. This proposal aims to test novel models of how packaging of DNA in the nucleus plays a fundamental role in gene expression. Understanding these concepts is important in the context of successful gene therapy where major hurdles need to be overcome. This work also has implications for somatic cell therapy since it is important to understand how genes are expressed in order to successfully reprogram cells. Both of these ....New models for the role of chromatin in controlling inducible gene expression. This proposal aims to test novel models of how packaging of DNA in the nucleus plays a fundamental role in gene expression. Understanding these concepts is important in the context of successful gene therapy where major hurdles need to be overcome. This work also has implications for somatic cell therapy since it is important to understand how genes are expressed in order to successfully reprogram cells. Both of these areas are important to the Biotechnology industry. Answering questions about higher order chromatin structure in gene transcription will provide cutting edge, innovative knowledge that will have international significance. Read moreRead less
A novel granular stress sensor for soil exploration. The project aims to develop a novel way to measure the state of soils and improve the perception of soft ground robots by combining advances in sensor development with granular physics. The project expects to produce new insights in geotechnical engineering by utilising innovative sensors compliant with the surrounding medium, thus improving measurements across broader deformation conditions than existing technologies. Expected outcomes includ ....A novel granular stress sensor for soil exploration. The project aims to develop a novel way to measure the state of soils and improve the perception of soft ground robots by combining advances in sensor development with granular physics. The project expects to produce new insights in geotechnical engineering by utilising innovative sensors compliant with the surrounding medium, thus improving measurements across broader deformation conditions than existing technologies. Expected outcomes include an increased ability to prevent soil failures by utilising these sensors to monitor stress levels underground. This should provide significant benefits for saving critical infrastructure from environmental and geotechnical failures, including landslides, tunnel collapses, and tailings dam damages.Read moreRead less
The Social Life of Death. This project aims to investigate experiences of death, dying and bereavement amidst rapid social, economic and political transformation. In the wake of COVID19, and as Australia’s anticipated ‘death boom’ approaches, how to foster good deaths has never been more uncertain, nor more urgent. Drawing on innovative methods and socio-cultural theory, and working in partnership with families and communities, this project aims to generate new knowledge to better inform and imp ....The Social Life of Death. This project aims to investigate experiences of death, dying and bereavement amidst rapid social, economic and political transformation. In the wake of COVID19, and as Australia’s anticipated ‘death boom’ approaches, how to foster good deaths has never been more uncertain, nor more urgent. Drawing on innovative methods and socio-cultural theory, and working in partnership with families and communities, this project aims to generate new knowledge to better inform and improve policy and spark cultural renewal around the end of life. Expected outcomes include setting the international benchmark for novel scholarly understandings of death, dying and bereavement, and centring community voices in addressing contemporary challenges to dying well.
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Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Origin and evolution of genes on the human X chromosome. Two groups of functionally related genes are found on the human X chromosome in disproportionately high numbers. I will test whether an uneven distribution of genes is common in mammalian genomes, or whether the human X is special. I will test hypotheses of how the gene groups arose on the human X by comparing their location and expression patterns in other mammals, and other vertebrates. It will then be clear whether the ancestral autosom ....Origin and evolution of genes on the human X chromosome. Two groups of functionally related genes are found on the human X chromosome in disproportionately high numbers. I will test whether an uneven distribution of genes is common in mammalian genomes, or whether the human X is special. I will test hypotheses of how the gene groups arose on the human X by comparing their location and expression patterns in other mammals, and other vertebrates. It will then be clear whether the ancestral autosome was ?chosen?, whether it ?selfishly? accumulated these genes, or whether the function of genes changed in response to selective pressures.Read moreRead less