Investigating Wnt signaling during human nephron commitment and patterning. Aims: To use gene edited stem cell lines that display cell location, identity and cell state to map human kidney tissue formation in the laboratory. By monitoring how each cell responds to those around it across time and space, we will for the first time map the formation of kidney tissue in the dish.
Significance: Understanding how stem cells form a tissue will help us to improve and control the process. This is key to ....Investigating Wnt signaling during human nephron commitment and patterning. Aims: To use gene edited stem cell lines that display cell location, identity and cell state to map human kidney tissue formation in the laboratory. By monitoring how each cell responds to those around it across time and space, we will for the first time map the formation of kidney tissue in the dish.
Significance: Understanding how stem cells form a tissue will help us to improve and control the process. This is key to advancing tissue engineering.
Expected outcomes: The proposal will pioneer state-of-the-art imaging, gene editing and machine learning approaches, generating models of human development that are currently unavailable.
Benefits: This understanding will guide the development of novel approaches to tissue engineering.
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Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolu ....Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolution crystal structures are being used to identify function. Intriguingly, preliminary data indicates that the mutations do not affect the native antibody structure, but rather influence dynamic states. The project plans to use a combination of mutagenesis, molecular dynamics simulation and deuterium exchange to study antibody dynamics.Read moreRead less
Design and Fabrication of Molecular Machines: the Nanomachines of the Future. Nanotechnology that incorporates the use of nanomachines and molecular machines is an exciting new area of translational research, with broad potential in biomedical technology and industrial applications. We are developing new molecular machines and optimising their assembly. Recent innovation in the world of nanotechnology concerns the design and manufacture of synthetic and hybrid machines, based on existing biologi ....Design and Fabrication of Molecular Machines: the Nanomachines of the Future. Nanotechnology that incorporates the use of nanomachines and molecular machines is an exciting new area of translational research, with broad potential in biomedical technology and industrial applications. We are developing new molecular machines and optimising their assembly. Recent innovation in the world of nanotechnology concerns the design and manufacture of synthetic and hybrid machines, based on existing biological molecular machines but incorporating synthetic parts. Australia has an opportunity to be at the forefront of these new developments in nanotechnology, with a new generation of Australian scientists being trained across the foundation disciplines of chemistry, physics and molecular biology.Read moreRead less
Surveillance of the mechanisms controlling proteome foldedness. This project aims to measure how cells keep the proteome folded. Cells have extensive quality control networks to govern synthesis, folding and transport of every protein but the buffering capacity of this system is not definable. This capacity is needed to understand how problems arise in managing proteome foldedness, a central feature of human diseases and biotechnology and synthetic biology applications that need cell-based produ ....Surveillance of the mechanisms controlling proteome foldedness. This project aims to measure how cells keep the proteome folded. Cells have extensive quality control networks to govern synthesis, folding and transport of every protein but the buffering capacity of this system is not definable. This capacity is needed to understand how problems arise in managing proteome foldedness, a central feature of human diseases and biotechnology and synthetic biology applications that need cell-based production of engineered proteins such as hormones and antibodies. The outcomes are expected to provide basic knowledge of this fundamental process and provide biosensors and screening methods for use in health and biotechnology industries.Read moreRead less
Spatio-temporal activation of genes in cells and mice. This project aims to develop novel genetic methods and instrumentation for the local, rapid and reversible activation of genes in cells and mice. This project expects to generate highly innovative light- and sound-based technologies that will permit to study living systems on the gene-level with unprecedented precision. Expected outcomes include new research and technology capacity to broadly address fundamental biological questions and to c ....Spatio-temporal activation of genes in cells and mice. This project aims to develop novel genetic methods and instrumentation for the local, rapid and reversible activation of genes in cells and mice. This project expects to generate highly innovative light- and sound-based technologies that will permit to study living systems on the gene-level with unprecedented precision. Expected outcomes include new research and technology capacity to broadly address fundamental biological questions and to create new applied processes. This project intends to provide significant benefits, such as enhanced knowledge generation, multidisciplinary training opportunities and patentable technologies.Read moreRead less
The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity f ....The hidden secondary metabolite biosynthetic potential of fungi. This proposal aims to develop synthetic biology tools to allow rapid access to the hidden metabolites encoded in fungal genomes and discover how they interact with plant and animal hosts. Genome sequencing reveals that fungi harbour vast hidden potential for biosynthesis of bioactive small molecules. The lack of tools to efficiently access this hidden potential has hindered the ability to develop this uncharted chemical diversity for pharmaceutics and agriculture, and understand their biological roles in pathogens. Expected outcomes include sources of bioactive molecules and better management of fungal diseases in crops and humans.Read moreRead less
ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and ne ....ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and new to nature biological pathways and enzymes. CoESB will combine engineering with molecular biology to design and construct novel biological systems that can convert biomass from agriculture or waste streams to biofuel, bioplastics and other high-value chemicals.Read moreRead less
Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors w ....Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors will be used to devise a simple portable colorimetric test that can be performed in the vineyard or the winery. The ability to rapidly determine the level of grape contamination with phenolic glucosides would give Australian wine growers and wine makers a powerful tool to mitigate the effects of bushfires.Read moreRead less
Engineered plant receptors as orthogonal neuronal switches. This project aims to develop synthetic biology methods to study brain function by utilising engineered plant receptors. This project will expand our ability to manipulate nerve cell function with high specificity and without side effects in freely behaving animals. Plant receptors will be developed into molecular tools in an iterative process that improves key properties using rational protein design. Expected outcomes include innovativ ....Engineered plant receptors as orthogonal neuronal switches. This project aims to develop synthetic biology methods to study brain function by utilising engineered plant receptors. This project will expand our ability to manipulate nerve cell function with high specificity and without side effects in freely behaving animals. Plant receptors will be developed into molecular tools in an iterative process that improves key properties using rational protein design. Expected outcomes include innovative and broadly-applicable neuroscience methods and an understanding of receptors involved in plant growth and defense. Benefits of this project include an enhanced capacity to generate knowledge, multidisciplinary training opportunities and patentable synthetic biology technologies.Read moreRead less
A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societa ....A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societal benefit as a fundamental scientific platform, improving Australia's capacity and impact in the agriculture and the healthcare sectors. The platform technology has the potential to increase the quality of life for patients and their carers, while also produce fitter, healthier livestock.Read moreRead less