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
Discovery Early Career Researcher Award - Grant ID: DE230101081
Funder
Australian Research Council
Funding Amount
$458,238.00
Summary
Developing CRISPR Prime Editing for highly efficient precise gene editing. This project will further develop a recent breakthrough in gene editing technology named CRISPR prime editing to improve its performance in generating specific genome modifications in cells and organisms. This project expects to generate new knowledge regarding optimal strategies for its deployment as well as create novel enhanced versions of the technology. This would significantly enhance our ability to perform precise ....Developing CRISPR Prime Editing for highly efficient precise gene editing. This project will further develop a recent breakthrough in gene editing technology named CRISPR prime editing to improve its performance in generating specific genome modifications in cells and organisms. This project expects to generate new knowledge regarding optimal strategies for its deployment as well as create novel enhanced versions of the technology. This would significantly enhance our ability to perform precise genome modification of organisms and lead to substantial benefits for a vast array of applications in fundamental and applied biology. Future applications will include generating mutations in cells and model organisms for basic research and creating genetically enhanced agricultural animals or plants.Read moreRead less
Flipping the mattress: infinite polyurethane recycling by synthetic biology. Australia is covered in billions of tonnes of plastic and yet <10% is recycled today. Polyurethane (PU) is ubiquitous in our everyday lives, from lacquer coatings to elastane clothing to durable foam padding in car seats, cushions and mattresses. Currently, there are few avenues for PU recycling and much ends up in landfill e.g., a single mattress produces 15-20kg of PU foam waste. Luckily, biodegradation of PU can occu ....Flipping the mattress: infinite polyurethane recycling by synthetic biology. Australia is covered in billions of tonnes of plastic and yet <10% is recycled today. Polyurethane (PU) is ubiquitous in our everyday lives, from lacquer coatings to elastane clothing to durable foam padding in car seats, cushions and mattresses. Currently, there are few avenues for PU recycling and much ends up in landfill e.g., a single mattress produces 15-20kg of PU foam waste. Luckily, biodegradation of PU can occur naturally via various microbial means and from insects, like Galleria mellonella larvae. The overall aim of this research project is to understand plastic biodegradation and translate nature’s solutions into flexible and efficient synthetic enzyme technologies that can sustainably recycle commonly used PU foams. Read moreRead less
Synthetic biology tools for integration into bacterial chromosomes. The aim of the project is to develop a set of versatile chromosomal integration tools for bacteria, enabling rapid development of novel biological outputs. A major goal in the emerging discipline of synthetic biology is to apply engineering principles to the design and construction of new biological entities such as proteins, genetic circuits and cells. Custom-designed genetic circuits, integrated in an appropriate host genome, ....Synthetic biology tools for integration into bacterial chromosomes. The aim of the project is to develop a set of versatile chromosomal integration tools for bacteria, enabling rapid development of novel biological outputs. A major goal in the emerging discipline of synthetic biology is to apply engineering principles to the design and construction of new biological entities such as proteins, genetic circuits and cells. Custom-designed genetic circuits, integrated in an appropriate host genome, hold enormous economic potential for applications ranging from biomedicine to biofuel production. This project aims to help synthetic biologists to embed made-to-order circuits in appropriate host cells to act as living factories, potentially replacing industrial processes which are currently environmentally and economically costly.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
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
Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set ....Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set of protease-based signal transducers and ligand activated allosteric receptors will be created. The developed components are intended to be used to construct artificial signaling networks in mammalian cells that are orthogonal to the endogenous signaling cascades.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.