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
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
Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A b ....Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A better understanding of gene regulation in malaria parasites will help us to better combat the tricks utilised by this and other organisms to elude our immune systems.Read moreRead less
Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international effo ....Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international efforts in this area, via the development of statistical methods for segmenting genomes, classification of those segments, and study of the resulting classes. In the long term, enhanced understanding of eukaryotic cells will lead to breakthroughs in biology, and to medical, pharmaceutical, agricultural and scientific advances.Read moreRead less
Enhancing sleep and wellbeing in working families. This project aims to investigate the role of sleep on individuals’ health by measuring Australians' sleep patterns relative to work and family demands. This project expects to generate new knowledge in the sociology of sleep using innovative data collection bringing together cross-national, nationally representative, longitudinal and physiological data on Australians’ sleep patterns. Expected outcomes of this project are to identify the social a ....Enhancing sleep and wellbeing in working families. This project aims to investigate the role of sleep on individuals’ health by measuring Australians' sleep patterns relative to work and family demands. This project expects to generate new knowledge in the sociology of sleep using innovative data collection bringing together cross-national, nationally representative, longitudinal and physiological data on Australians’ sleep patterns. Expected outcomes of this project are to identify the social and biological determinants of sleep and their links with health, family and economic policy recommendations.Read moreRead less
Characterisation of Genes involved in Secondary Metabolism in the Blackleg Pathogen of Canola. Blackleg caused by the fungus Leptosphaeria maculans is the major disease of canola. In spite of the economic importance of this fungus, little is known about its metabolic pathways, its genes and how they are organised. We have sequenced a large piece of L. maculans DNA comprising eight genes, including a regulatory gene and one that may be may be involved in producing secondary metabolites such as ....Characterisation of Genes involved in Secondary Metabolism in the Blackleg Pathogen of Canola. Blackleg caused by the fungus Leptosphaeria maculans is the major disease of canola. In spite of the economic importance of this fungus, little is known about its metabolic pathways, its genes and how they are organised. We have sequenced a large piece of L. maculans DNA comprising eight genes, including a regulatory gene and one that may be may be involved in producing secondary metabolites such as phytotoxins. We will determine the role of these genes in metabolism and the disease process, thus providing insights into secondary metabolism and gene regulation in this important plant pathogen.Read moreRead less
Violence, Religion and Well-being in Contemporary Burma (Myanmar): A Medical Anthropological Study of Everyday Life Under Dictatorship. For 40 years, Burma has been controlled by a military dictatorship with human rights abuses occurring daily. Terror and political violence are used as tools of repression. An in-depth ethnographic study will be conducted into the relationship between emotional/psychological distress and the violence and fear that pervades everyday Burmese life. The project will ....Violence, Religion and Well-being in Contemporary Burma (Myanmar): A Medical Anthropological Study of Everyday Life Under Dictatorship. For 40 years, Burma has been controlled by a military dictatorship with human rights abuses occurring daily. Terror and political violence are used as tools of repression. An in-depth ethnographic study will be conducted into the relationship between emotional/psychological distress and the violence and fear that pervades everyday Burmese life. The project will test the hypothesis that religion plays an important role in mediating responses to fear. No other study has been conducted of everday life under this dictatorship, or of survival strategies created to alleviate fear. Outcomes will include refereed articles, a major monograph on the subject and the development of a new methodology appropriate for aiding victims of terror and torture.Read moreRead less
The sociology of antibiotics and the antimicrobial resistance crisis. This project aims to investigate the sociological dimensions of antibiotics consumption by examining the views and experiences of clinicians, decision-makers, and members of the general population. The project expects to generate new knowledge about the social aspects of antibiotics use and consumer-provider interactions. Expected outcomes of this project include stronger consumer-provider collaborations about antibiotic use a ....The sociology of antibiotics and the antimicrobial resistance crisis. This project aims to investigate the sociological dimensions of antibiotics consumption by examining the views and experiences of clinicians, decision-makers, and members of the general population. The project expects to generate new knowledge about the social aspects of antibiotics use and consumer-provider interactions. Expected outcomes of this project include stronger consumer-provider collaborations about antibiotic use and a new evidence-base to guide policy decisions. This project should provide significant benefits for the national response to antimicrobial resistance, including enhanced public education and public policy.Read moreRead less
Understanding how cells compact and segregate DNA in vertebrates. How a cell compacts and divides its DNA is still a major unanswered question in biology. This project will determine the way in which a cell compacts its DNA nearly ten thousand fold to allow the faithful and accurate segregation to daughter nuclei.