Sculpting a masterpiece: synthesis and evolution of minimal yeast genomes. This project aims to better understand genome complexity by engineering minimal yeast genomes that have fewer genes, and are therefore easier to characterise and engineer. Yeast is a model organism and industrial food, fuel, and chemical producer. This project expects to increase our basic understanding of yeast genomes, and develop new tools for engineering whole genomes. Expected outcomes of this project include the eng ....Sculpting a masterpiece: synthesis and evolution of minimal yeast genomes. This project aims to better understand genome complexity by engineering minimal yeast genomes that have fewer genes, and are therefore easier to characterise and engineer. Yeast is a model organism and industrial food, fuel, and chemical producer. This project expects to increase our basic understanding of yeast genomes, and develop new tools for engineering whole genomes. Expected outcomes of this project include the engineering and characterisation of the world's first minimal yeast genome, and the development of novel industrial yeast strains. This will provide significant benefits for both fundamental genetics and biochemistry research, and the industrial use of yeast for bio-manufacturing of sustainable foods, fuels, and chemicals.Read moreRead less
A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synt ....A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synthetic biology techniques to characterise, modify and express saxitoxin biosynthesis pathways, thereby providing a sustainable source of toxin analogues of value to industry and research. This novel 'green technology' will benefit the environment, human health and the Australian economy.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100608
Funder
Australian Research Council
Funding Amount
$359,000.00
Summary
Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibod ....Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibodies resistant to aggregation. Preliminary data indicates that stabilising mutations improves the biophysical properties of monoclonals without affecting the native antibody structure. The project aims to provide detailed insights into the molecular basis of antibody stability.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100016
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Synthetic Biology: from Genomics to Valuable Bioproducts. Genomics has led to the discovery of both the fine and gross characteristics of specific microbial physiologies. This project aims to take the genetic diversity inherent in microbial systems and exploit it for biotechnology applications, using the cutting-edge facilities available for synthetic biology. The acquisition of a long-read sequencing platform, droplet digital PCR machine, pulsed-field electrophoresis apparatus, DNA library syst ....Synthetic Biology: from Genomics to Valuable Bioproducts. Genomics has led to the discovery of both the fine and gross characteristics of specific microbial physiologies. This project aims to take the genetic diversity inherent in microbial systems and exploit it for biotechnology applications, using the cutting-edge facilities available for synthetic biology. The acquisition of a long-read sequencing platform, droplet digital PCR machine, pulsed-field electrophoresis apparatus, DNA library system and small scale bioreactor will address the limitations of short-read sequencing, large fragment cloning and gene expression technologies, currently creating bottlenecks for synthetic biologists.Read moreRead less
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
Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonst ....Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonstrates that such a primordial receptor can in principle be reconstructed and characterised. The project proposes to expand this work, which will provide intriguing insights into antigen receptor evolution. The reconstruction of basic recognition modules will also be highly beneficial for biosensor applications. Read moreRead less
Artificially building the bacterial flagellar motor. This project will allow us to learn how nature’s most sophisticated rotary motor works and how to build these artificially, establishing a new field of research into man-made biological machines. This has potential applications for the emerging field of nanotechnology to make nanometre-scale devices that are powered by efficient biological machines.
From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this proj ....From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this project include new manufacturing processes for chemicals and foods, discovery of novel metabolism in yeast, and enhanced collaboration between Australia, Denmark, and the United States. This Project will provide benefits through sustainable bio-manufacturing, new economic activity, and reduced greenhouse gas emissions.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100262
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Artificial synthesis of bacteria's molecular syringe. The type III secretion system. The type III secretion system is an impressive protein superstructure consisting of hundreds of subunits that act cooperatively to specifically inject virulence factors directly into the cytoplasm of host cells. Its size and complexity make it a formidable challenge to understand at a molecular level with conventional methods. This project adopts a fundamentally new approach that will put Australian science in t ....Artificial synthesis of bacteria's molecular syringe. The type III secretion system. The type III secretion system is an impressive protein superstructure consisting of hundreds of subunits that act cooperatively to specifically inject virulence factors directly into the cytoplasm of host cells. Its size and complexity make it a formidable challenge to understand at a molecular level with conventional methods. This project adopts a fundamentally new approach that will put Australian science in the spotlight of a highly active research field. Artificial synthesis of bacteria's molecular syringe using DNA nanotechnology will revolutionise its study by providing unprecedented dexterity in its manipulation and, for the first time, allow the isolation of functional subcomplexes for high-resolution structural studies.Read moreRead less
A scalable, synthetic retina: signal processing in droplet systems with DNA. This project aims to design DNA-based nanotechnology for processing optical signals in synthetic biological systems. The intended outcome of this project is to develop a system for signal transduction in artificial bilayers using new DNA nanostructures. The anticipated goal of the project is to deliver: 1) light-based control of membrane protein insertion into artificial bilayers; 2) novel DNA-based pores that can trans ....A scalable, synthetic retina: signal processing in droplet systems with DNA. This project aims to design DNA-based nanotechnology for processing optical signals in synthetic biological systems. The intended outcome of this project is to develop a system for signal transduction in artificial bilayers using new DNA nanostructures. The anticipated goal of the project is to deliver: 1) light-based control of membrane protein insertion into artificial bilayers; 2) novel DNA-based pores that can transduce signals across membranes; 3) signal processing using multi-compartment biological components composed. Together, this technology allows us to use light and external signals to control biochemical pathways in synthetic systems.Read moreRead less