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
MOLECULAR BREEDING OF CYTOCHROME P450 ENZYMES. Cytochrome P450s are enzymes that catalyse an impressive array of oxidative transformations. However, there is little available data on how to modify their substrate specificity and generate tailored biocatalysts. We plan to use an emerging technology known as DNA shuffling to create libraries of P450s with varying activities. These will then be screened for enzymes that can catalyse the formation of indigo (a blue dye) and indirubin (a chemother ....MOLECULAR BREEDING OF CYTOCHROME P450 ENZYMES. Cytochrome P450s are enzymes that catalyse an impressive array of oxidative transformations. However, there is little available data on how to modify their substrate specificity and generate tailored biocatalysts. We plan to use an emerging technology known as DNA shuffling to create libraries of P450s with varying activities. These will then be screened for enzymes that can catalyse the formation of indigo (a blue dye) and indirubin (a chemotherapeutic agent). The enzymes that catalyse indigo formation will be useful in the production of coloured transgenic plants and those that produce indirubin will have a role in gene therapy.Read moreRead less
The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemis ....The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemistry and spectroscopy will be used. This will be the first time that the enzymes of bacterial Mn2+-oxidation will have been characterised in such detail and will lead to a greater understanding of the process of bacterial manganese oxidation.Read moreRead less
A molecular timer for inflammation and cell death. This project aims to improve our understanding of the timely function of the immune system. Most processes fundamental to life rely on the timely execution of cellular functions. One biological system in which timing is paramount is the immune system. Organismal health relies upon this front-line defence system for rapidly detecting invading microbes and inducing an appropriate, and timely, antimicrobial response to clear infection. We do not cu ....A molecular timer for inflammation and cell death. This project aims to improve our understanding of the timely function of the immune system. Most processes fundamental to life rely on the timely execution of cellular functions. One biological system in which timing is paramount is the immune system. Organismal health relies upon this front-line defence system for rapidly detecting invading microbes and inducing an appropriate, and timely, antimicrobial response to clear infection. We do not currently understand how immune responses are temporally coordinated. This proposal aims to address this key knowledge gap by characterising a novel molecular timer that dictates the co-ordinated timing of immune responses and immune cell death. These studies may yield fundamental insight into mammalian anti-microbial mechanisms.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowle ....Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of developmental biology.
Read moreRead less
EnzOnomy - an enzyme-based production pipeline for the bioeconomy. The sustainable production of high value chemicals (e.g. fuels, foods) from renewable materials is a cornerstone for the emerging global bioeconomy. We aim to harness the potential of protein engineering to develop a technology (EnzOnomy) to convert renewable raw material (e.g. sugar) into platform chemicals (e.g. isobutanol, a building block for jet fuels, fibers, plastics and antioxidants). Our multi-disciplinary and well estab ....EnzOnomy - an enzyme-based production pipeline for the bioeconomy. The sustainable production of high value chemicals (e.g. fuels, foods) from renewable materials is a cornerstone for the emerging global bioeconomy. We aim to harness the potential of protein engineering to develop a technology (EnzOnomy) to convert renewable raw material (e.g. sugar) into platform chemicals (e.g. isobutanol, a building block for jet fuels, fibers, plastics and antioxidants). Our multi-disciplinary and well established international team will link scientific progress to markets to enhance potential commercial impact in the bioeconomy. The project thus provides great benefit for our nation as it embeds Australia in technologies and global networks that will cement its leading position to safe-guard the future of our planet.
Read moreRead less
Development of technologies to monitor multimolecular complexes. Development of technologies to monitor multimolecular complexes. This project aims to develop technologies to monitor how proteins and their interacting molecules (such as hormones) form multi-component complexes, and how these complexes function in the cell, including movement from the cell surface, into different cellular compartments and back up to the surface. These technologies are expected to enable monitoring in live cells i ....Development of technologies to monitor multimolecular complexes. Development of technologies to monitor multimolecular complexes. This project aims to develop technologies to monitor how proteins and their interacting molecules (such as hormones) form multi-component complexes, and how these complexes function in the cell, including movement from the cell surface, into different cellular compartments and back up to the surface. These technologies are expected to enable monitoring in live cells in real-time with high sensitivity. This project could have broad benefits for and affect study of all aspects of the life sciences at the cellular and molecular levels. How these protein complexes function in cells underpins much of our understanding of biology, and technological tools.Read moreRead less
An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven mol ....An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven molecular collisions on nano-bioengineered surfaces. This provides significant benefits, creating new knowledge in nanomaterials and advanced manufacturing of nanofabricated devices, creating commercial interest and positioning Australia at the forefront of molecular discovery technology, a highly valuable global market.
Read moreRead less
Venomics: Molecular and functional analysis of Australian snake venoms for development of human therapeutics. Australian snake venoms are lethal cocktails with potent effects on mammalian physiological processes, designed to immobilize and kill prey animals. Major targets of venom components are the nervous and blood coagulation systems but there is reason to believe that venoms have many other as yet unrecognized effects on mammalian systems. The project will combine techniques of modern mole ....Venomics: Molecular and functional analysis of Australian snake venoms for development of human therapeutics. Australian snake venoms are lethal cocktails with potent effects on mammalian physiological processes, designed to immobilize and kill prey animals. Major targets of venom components are the nervous and blood coagulation systems but there is reason to believe that venoms have many other as yet unrecognized effects on mammalian systems. The project will combine techniques of modern molecular biology (particularly transcriptomics and proteomics) with functional and structural analysis of purified venom components. Venoms from approximately 20 Australian snakes will be studied to reveal lead compounds for improved human pharmaceuticals against common disorders such as high blood pressure, bleeding and stroke.Read moreRead less