High-resolution multiscale modelling of pandemics: COVID-19 and beyond. The project aims to develop high-resolution computational models for pandemic mitigation and control, focussing on the novel coronavirus and its emerging variants, and leveraging demographic, genomic and epidemiological data. It expects to rigorously compare multi-scale effects of complex vaccination and social distancing strategies and quantify optimal responses under the COVID-19 induced uncertainty. The intended outcomes ....High-resolution multiscale modelling of pandemics: COVID-19 and beyond. The project aims to develop high-resolution computational models for pandemic mitigation and control, focussing on the novel coronavirus and its emerging variants, and leveraging demographic, genomic and epidemiological data. It expects to rigorously compare multi-scale effects of complex vaccination and social distancing strategies and quantify optimal responses under the COVID-19 induced uncertainty. The intended outcomes include computational models of how the most infectious viral variants emerge and spread in presence of interventions, how to predict the outbreaks, and which are the most vulnerable communities. This should make a significant economic and social impact, improving population health while maintaining a resilient economy.Read moreRead less
Quantifying emergence and dynamics of foodborne epidemics in Australia. The project aims to greatly improve the accuracy and scope of computational epidemiological models predicting emergence and evolution of foodborne diseases in Australia. It expects to reveal key pathways for both biological evolution of microorganisms, and their spread though food supply chains and human interactions. The intended outcomes include discovering how the most dominant strains of foodborne infection emerge and se ....Quantifying emergence and dynamics of foodborne epidemics in Australia. The project aims to greatly improve the accuracy and scope of computational epidemiological models predicting emergence and evolution of foodborne diseases in Australia. It expects to reveal key pathways for both biological evolution of microorganisms, and their spread though food supply chains and human interactions. The intended outcomes include discovering how the most dominant strains of foodborne infection emerge and self-organise in complex networks, how to predict and contain the epidemics closer to their source, and which are the most vulnerable groups and communities. This should make a significant economic and social impact, improving health of the population, while also safeguarding national and international supply chains.Read moreRead less
Multiscale models in immuno-epidemiology. The spread of a pathogen (for example, a virus or bacteria) through a population is a multi-scale phenomena, influenced by factors acting at both the population and within-host scales. At the population scale, transmission is influenced by how infectious an infected host is. Infectiousness in turn depends on the balance between pathogen replication within the host and immune/drug control mechanisms. This project aims to develop new mathematical framework ....Multiscale models in immuno-epidemiology. The spread of a pathogen (for example, a virus or bacteria) through a population is a multi-scale phenomena, influenced by factors acting at both the population and within-host scales. At the population scale, transmission is influenced by how infectious an infected host is. Infectiousness in turn depends on the balance between pathogen replication within the host and immune/drug control mechanisms. This project aims to develop new mathematical frameworks for simultaneously modelling these two scales. This will provide a platform for the rigorous study of complex biological interactions - such as the emergence and combat of drug-resistance - that shape society's ability to control infectious diseases in human, animal and plant systems.Read moreRead less
The cellular basis of sex-specific responses to virus infection. This project aims to explore how the sex of cells impacts virus infections in culture. To date, the sex of cells in culture has been overlooked as an important source of biological variability, but may be found to affect basic science through to anti-viral drug discovery. Using a model in which a virus can be adapted to grow better in cells of a single sex, this project expects to generate new knowledge about how sex differences im ....The cellular basis of sex-specific responses to virus infection. This project aims to explore how the sex of cells impacts virus infections in culture. To date, the sex of cells in culture has been overlooked as an important source of biological variability, but may be found to affect basic science through to anti-viral drug discovery. Using a model in which a virus can be adapted to grow better in cells of a single sex, this project expects to generate new knowledge about how sex differences impact virus-host interactions. This project expects to provide new insights into sex-based differences in how cells detect and respond to virus infection, and the extent to which the sex of cells impacts viruses in general.Read moreRead less
Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develo ....Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develop innovative methods to investigate, and importantly modulate, DNA and RNA triple helix assembly, specificity and molecular interactions. Resulting insights will underpin novel approaches to gene regulation, principally in the context of designing new antibacterial agents to address the antibacterial resistance problem.Read moreRead less
Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel mol ....Roadblocks in DNA replication. This project aims to develop the technology to visualise and understand the molecular processes responsible for the faithful copying of cellular DNA in the presence of roadblocks caused by chemical pressures and competing intracellular events. Understanding this process is important as DNA replication is responsible for copying the DNA genetic blueprint of cells and is crucial to all life on earth. This project will have as key outcomes the development of novel molecular visualisation technology and the first molecular description of the dynamic processes used by the DNA-replication machinery to navigate roadblocks. These outcomes should provide significant benefits including enhanced collaboration and scientific capacity in Australia.Read moreRead less
Creation of a super-resolution map of the bacterial cytokinesis machinery . Cell division is a fundamental process essential for life. Yet our understanding of this process on a molecular level is limited, mostly hampered by the inability to visualize the different components of the division machinery inside these tiny cells with adequate resolution. To overcome this barrier, capitalizing on recent advancements in imaging and molecular technologies combined with innovative engineering, this proj ....Creation of a super-resolution map of the bacterial cytokinesis machinery . Cell division is a fundamental process essential for life. Yet our understanding of this process on a molecular level is limited, mostly hampered by the inability to visualize the different components of the division machinery inside these tiny cells with adequate resolution. To overcome this barrier, capitalizing on recent advancements in imaging and molecular technologies combined with innovative engineering, this project aims to create a spatial and temporal map of the division machinery inside bacterial cells at unprecedented resolution. The expected outcomes are new knowledge on the mechanism of bacterial division and technological advances in biological imaging, informing applications in a wide variety of sectors.Read moreRead less
Peril and promise: Origins and spread of integron gene cassettes. Integrons have a major role in spreading antibiotic resistance genes among pathogens. They do so by capturing gene cassettes encoding resistance, yet how these cassettes are generated, the taxa in which they originate, and the range of traits that cassettes can encode have been outstanding questions for 30 years. This project addresses these long standing questions. The project will analyze single bacterial cells to detect newly ....Peril and promise: Origins and spread of integron gene cassettes. Integrons have a major role in spreading antibiotic resistance genes among pathogens. They do so by capturing gene cassettes encoding resistance, yet how these cassettes are generated, the taxa in which they originate, and the range of traits that cassettes can encode have been outstanding questions for 30 years. This project addresses these long standing questions. The project will analyze single bacterial cells to detect newly generated cassettes and assign them to specific taxa, using an innovative method that links cassette DNA to bacterial 16S rDNA. Understanding cassette origins is the key to controlling their activity, both to harness integrons for biotechnology, and to prevent pathogens from acquiring new, dangerous traits. Read moreRead less
Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others a ....Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others are used in biotechnology for biosynthetic chemical production or bioremediation. This project expects to help the future development of new antibiotics and assist in the design of strains to be used in biotechnological applications.Read moreRead less
Determining features that separate groups of protein sequences. This project aims to develop mathematical approaches for determining features that distinguish one group of proteins from another, based on their amino acid sequences. The groups of sequences will reflect different outcomes, so that identifying the fundamental features can result in targeted interventions against the poorer outcome. A simple comparison at each position or of known features can fail to determine robust differentiator ....Determining features that separate groups of protein sequences. This project aims to develop mathematical approaches for determining features that distinguish one group of proteins from another, based on their amino acid sequences. The groups of sequences will reflect different outcomes, so that identifying the fundamental features can result in targeted interventions against the poorer outcome. A simple comparison at each position or of known features can fail to determine robust differentiators and so more complex methods are required. The project will, for example, help identify HIV vaccine targets by comparing early HIV transmission sequences from those in chronic infection. The methods will be applicable to viral proteins where high mutation rates make this task even more complex.Read moreRead less