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
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
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
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.
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
Microbial junk food: developing synthetic platforms for plastic degradation. This project aims to establish the genetic basis of polyethelene biodegradation (PED) by microbes from the gut microbiome of plastic-eating caterpillars. It will transform the active microbial PED genes into carefully designed synthetic microbes for efficient, safe and large-scale PED. The project will combine innovative functional microbial genetic tools and synthetic biology techniques with solid biochemistry and bioi ....Microbial junk food: developing synthetic platforms for plastic degradation. This project aims to establish the genetic basis of polyethelene biodegradation (PED) by microbes from the gut microbiome of plastic-eating caterpillars. It will transform the active microbial PED genes into carefully designed synthetic microbes for efficient, safe and large-scale PED. The project will combine innovative functional microbial genetic tools and synthetic biology techniques with solid biochemistry and bioinformatics to produce translatable synthetic platforms containing key genes optimised for efficient PE waste removal. The outcomes will have the potential to transform the relative ineffective and expensive current methods for PE disposal into flexible, cost-effective and sustainable solutions applicable to multiple sectors.Read moreRead less
Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of sy ....Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of synthetic encapsulin-Rubisco carbon-fixing nanoreactors and transform them into leaf chloroplasts to test their impact on plant photosynthesis and growth. Our genetically simpler solution will aid ongoing global efforts to deliver overdue step change improvements in agricultural productivity.Read moreRead less