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.
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
Phage display derived antibody fragments for membrane protein research. Membrane proteins are key components of all living organisms and represent more than 50 per cent of all drug targets. This project will redefine the way membrane proteins are studied and will be highly beneficial to basic research, human disease and the biotechnology industry.
Discovery and characterisation of novel lanthipeptide biopreservatives. The aim of this project is to advance fundamental knowledge of microbial metabolism and provide natural anti-microbial molecules to the Australian food industry. A quarter of the world’s food supply is lost because of microbiological spoilage. Some chemical preservatives have been developed to combat food spoilage organisms, however their chronic impact on human health is the subject of debate. Consumer demand for safe and n ....Discovery and characterisation of novel lanthipeptide biopreservatives. The aim of this project is to advance fundamental knowledge of microbial metabolism and provide natural anti-microbial molecules to the Australian food industry. A quarter of the world’s food supply is lost because of microbiological spoilage. Some chemical preservatives have been developed to combat food spoilage organisms, however their chronic impact on human health is the subject of debate. Consumer demand for safe and natural alternatives is growing. Paradoxically, microbially-produced bioactive peptides may be the key to combating food spoilage organisms and food-borne pathogens. To this end, the project intends to develop an innovative strategy for the discovery, biosynthesis and characterisation of novel anti-microbial lanthipeptides.Read moreRead less
Single molecule spectroscopy-guided design of thermostable industrial enzymes. The production and engineering of proteins are key methodologies in life sciences. The current project aims to develop new approaches to accelerate the production and analysis of proteins and to apply them to discover improved proteins for use as feedstock supplements.
Heterologous expression of cyanobacterial compounds of analytical and therapeutic value. The project team has previously discovered the genetic basis for toxin production in cyanobacteria and algae. This project aims to define the biochemical pathways of the unique biosynthetic enzymes involved in alkaloid and cyclic peptide toxin production in these microorganisms. Via the development of large-gene cloning strategies, the toxins will be produced in a stable, sustainable and secure fermentation ....Heterologous expression of cyanobacterial compounds of analytical and therapeutic value. The project team has previously discovered the genetic basis for toxin production in cyanobacteria and algae. This project aims to define the biochemical pathways of the unique biosynthetic enzymes involved in alkaloid and cyclic peptide toxin production in these microorganisms. Via the development of large-gene cloning strategies, the toxins will be produced in a stable, sustainable and secure fermentation system. These compounds will be critical for standardising toxin detection methods in water supplies globally and for assessing their bioactivities in humans and other animals. Research students and the industry partner will also be trained to apply these novel biotechnologies for the production of other drug-like molecules.Read moreRead less