Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be use ....Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be used to construct and control purpose-built genetic networks and pathways. The results of this project are expected to add to the molecular tookit available to synthetic biologists.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101553
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
A flexible virus-like particle delivery platform for next-generation vaccines. Murine polyomavirus (MPyV) capsid proteins self-assemble into spherical protein shells approximately 45 nm in diameter. Such virus-like particles (VLPs) are of considerable interest as bionanotechnological tools. The unique flexibility provided by MPyV VLPs will be exploited by exploring the ability of the interior cavity to retain bioactive cargos while engineering novel functionality on the exterior surface by 'mix- ....A flexible virus-like particle delivery platform for next-generation vaccines. Murine polyomavirus (MPyV) capsid proteins self-assemble into spherical protein shells approximately 45 nm in diameter. Such virus-like particles (VLPs) are of considerable interest as bionanotechnological tools. The unique flexibility provided by MPyV VLPs will be exploited by exploring the ability of the interior cavity to retain bioactive cargos while engineering novel functionality on the exterior surface by 'mix-and-match' assembly of VLPs from modified components. As a proof of concept for next-generation vaccines that stimulate much needed, broadly protective responses against infectious diseases, model antigens will be delivered to specific immune cells using this nano-container.Read moreRead less
Nano-reactors: Protein cages as reusable scaffolds for designer enzymes. This project aims to develop robust protein cages derived from the coats of viruses to contain heat-stable P450 enzymes, for use as specialised protein bio-catalysts in chemical industries. A valuable chemical precursor of renewable bio-plastics will be produced from seed oils by enzymes, reducing the use of fossil fuels. This synthetic biology approach combines biotechnology, nanotechnology and protein engineering to estab ....Nano-reactors: Protein cages as reusable scaffolds for designer enzymes. This project aims to develop robust protein cages derived from the coats of viruses to contain heat-stable P450 enzymes, for use as specialised protein bio-catalysts in chemical industries. A valuable chemical precursor of renewable bio-plastics will be produced from seed oils by enzymes, reducing the use of fossil fuels. This synthetic biology approach combines biotechnology, nanotechnology and protein engineering to establish a plant-based platform biotechnology for using enzymes as catalysts to make high-value molecules. The project aims to show how to engineer clean, sustainable chemistry in designer nano-environments. This should make synthetic processes more sustainable and enhance advanced chemical manufacturing in Australia.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
The rational design and construction of new genetic circuits for applications in synthetic biology. By designing, building and testing new gene control modules, this project will gain an understanding of the design principles required for the construction of biological circuits with predictable and controllable behaviour. The ability to build such circuits will have significant economic benefit in areas such as metabolic engineering and biomedicine.
Discovery Early Career Researcher Award - Grant ID: DE150100091
Funder
Australian Research Council
Funding Amount
$341,000.00
Summary
Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexis ....Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexist on the DNA? The project aims to integrate systematic experiments using well-defined genetic components and mathematical modelling to understand the 'design' features of DNA and proteins that minimise these traffic problems. A better understanding could inform new strategies for manipulation of gene expression.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
Advancing programmable genetic computation to control plant gene activity. Plants can sense diverse internal and external conditions and integrate them to appropriately tune their response and maximize fitness. Plant biotechnology relies heavily on manipulating gene activity to change cell functions and confer advantageous agronomic traits. However, our ability to control plant gene activity remains rudimentary, limiting our biotechnology capabilities. This project aims to develop synthetic gene ....Advancing programmable genetic computation to control plant gene activity. Plants can sense diverse internal and external conditions and integrate them to appropriately tune their response and maximize fitness. Plant biotechnology relies heavily on manipulating gene activity to change cell functions and confer advantageous agronomic traits. However, our ability to control plant gene activity remains rudimentary, limiting our biotechnology capabilities. This project aims to develop synthetic gene logic gates in plants, to enable the construction of programmable genetically-encoded computational functions that can sense and process customizable inputs to drive desired changes in plant function. This advance will underpin useful applications in plant biotechnology such as improved crop stress tolerance and yield.Read moreRead less
In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-sele ....In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-selective incorporation are inefficient. The project’s strategy relies on the depletion of selected tRNAs from an in vitro protein translation system and their replacement with synthetic tRNAs, charged with unnatural amino acids. It is expected that the developed technology could be used to rapidly generate and screen highly diversified macrocyclic peptide libraries.Read moreRead less