Statistical methods and tools for integrative microarray analysis. Tools used for biological and medical research have been evolving and there has been an increase in high-throughput technologies such as genome sequencing and DNA microarray. The growing number of entries and the increasing availability of public microarray repositories and other sequence databases have generated the new challenge of developing tools to efficiently integrate data by different research groups. This research provi ....Statistical methods and tools for integrative microarray analysis. Tools used for biological and medical research have been evolving and there has been an increase in high-throughput technologies such as genome sequencing and DNA microarray. The growing number of entries and the increasing availability of public microarray repositories and other sequence databases have generated the new challenge of developing tools to efficiently integrate data by different research groups. This research provides new statistical methods to integrate different data sets. Its application in the biomedical field will allow researchers to effectively interpret the myriad of data generated within the community.Read moreRead less
Quantitative dynamics of functional magnetic resonance imaging. By modeling and verifying the dynamics of brain activity and blood flow that underlie functional magnetic resonance imaging (fMRI), this project will yield improved scientific outcomes and imaging sensitivity. The new data analysis techniques and technologies that result will yield potentially patentable intellectual property, and will increase the standing of Australia in this rapidly developing field, including via links being bu ....Quantitative dynamics of functional magnetic resonance imaging. By modeling and verifying the dynamics of brain activity and blood flow that underlie functional magnetic resonance imaging (fMRI), this project will yield improved scientific outcomes and imaging sensitivity. The new data analysis techniques and technologies that result will yield potentially patentable intellectual property, and will increase the standing of Australia in this rapidly developing field, including via links being built to leading international workers. The National Research Priority Goals of Frontier Technologies, Breakthrough Science, Smart Information Use, and Promoting an Innovation Economy will thus be advanced.Read moreRead less
Biophysics of the brain’s waste disposal system: Understanding why we sleep. This project aims to develop a new biophysical model of the brain, founded on the recently discovered glymphatic system responsible for waste disposal during sleep. It sets out to formulate, analyse, and validate rigorous new multiscale quantitative modelling – to advance the study of sleep and brain clearance dynamics, at timescales from hours to decades. Among expected outcomes are powerful models ready for applicatio ....Biophysics of the brain’s waste disposal system: Understanding why we sleep. This project aims to develop a new biophysical model of the brain, founded on the recently discovered glymphatic system responsible for waste disposal during sleep. It sets out to formulate, analyse, and validate rigorous new multiscale quantitative modelling – to advance the study of sleep and brain clearance dynamics, at timescales from hours to decades. Among expected outcomes are powerful models ready for application at both population and individual level, and testable predictions concerning the sleep patterns that lead to aggregation of waste in the brain and eventual cognitive decline. Project outcomes should also benefit society and the economy though translation into interventions for sleep disturbance – in future applied research.Read moreRead less
Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Development of Pyrrolopyrimidines as Inhibitors of ATP-Binding Proteins. This project seeks to generate analogues of natural products that have been found to be active against cancer cells and tropical parasites. The new materials produced by this project will aid in the study of biochemical processes involved in diseases such as cancer and lymphatic filariasis, thus leading the way to development of these compounds as potential treatments for such diseases.
Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that ma ....Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that may represent targets for therapeutic intervention. Additionally a precise understanding of the mechanisms of secretion of anchorless proteins will have an important impact in the biotechnology field, as new methodologies for the secretion of recombinant proteins of industrial value is a potential outcome.Read moreRead less
Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid i ....Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid in developing and designing artificial tactile sensors inspired by their biological models studied in this project. Long-term, the project is expected to make an original contribution towards developing new technologies and novel medical applications, both of which promise to be of great national benefit.Read moreRead less
Neural spike variability: unifying conflicting views of neural dynamics. The project aims to improve our understanding of neural dynamics. The brain represents and processes information by means of neural voltage spikes, which show great variability in their timing. Understanding the origin of such variable neural dynamics is a long-standing problem in neuroscience. The aim of this project is to develop a novel account of variable neural dynamics, unravelling their computational principles in th ....Neural spike variability: unifying conflicting views of neural dynamics. The project aims to improve our understanding of neural dynamics. The brain represents and processes information by means of neural voltage spikes, which show great variability in their timing. Understanding the origin of such variable neural dynamics is a long-standing problem in neuroscience. The aim of this project is to develop a novel account of variable neural dynamics, unravelling their computational principles in the brain, and unifying current leading but conflicting theories. The model developed in this project would be used to explain a range of empirical observations, and the principles unravelled would be applied to understand spike-timing based neural coding. The new knowledge gained in this project may have profound implications for designing brain-like computing devices.Read moreRead less
Retracing the Early Evolution of Metazoa using Novel Methods and Strategies. Metazoa is one of the best-characterised groups of species in terms of its morphology, fossil record, development, and genetic make-up, but the phylogeny remains obscure because the fossil record is incomplete and because molecular phylogenetic methods have not yet been developed with the complexity of genomic data in mind. We will develop methods and strategies for the analysis of whole genomes, and use them in studies ....Retracing the Early Evolution of Metazoa using Novel Methods and Strategies. Metazoa is one of the best-characterised groups of species in terms of its morphology, fossil record, development, and genetic make-up, but the phylogeny remains obscure because the fossil record is incomplete and because molecular phylogenetic methods have not yet been developed with the complexity of genomic data in mind. We will develop methods and strategies for the analysis of whole genomes, and use them in studies of the mitochondrial genome. We will infer the animal phylogeny, and use it to chart the evolution of animal morphology and development, and the evolution of mitochondrial genetic codes, gene order, and nucleotide content.Read moreRead less
Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidat ....Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidation in these events, the fundamental chemistry and biochemistry of protein oxidation is incompletely understood. This is addressed in this project. Knowledge of the mechanisms of these reactions is a vital pre-requisite to the rational design of preventative strategies that might enhance food quality, minimise UV damage and enhance human health.Read moreRead less