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
Australian Laureate Fellowships - Grant ID: FL210100071
Funder
Australian Research Council
Funding Amount
$3,246,000.00
Summary
“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics wo ....“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics work, as models for early steps in the evolution of cellular life, and as a significant new platform for the production of proteins and fine chemicals. Outcomes and benefits include improved understanding of how to generate new antibiotics, and the development of new platforms for Australian biotechnology and biocommerce.Read moreRead less
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
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and ....Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and validated platform technology for accelerating drug discovery and development. This should substantially reduce the costs associated with fighting human and animal diseases, leading to improved health, productivity and quality of life.Read moreRead less