Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein a ....Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein assembles without difficulty. This project will devise strategies for controlling this variability that will facilitate attempts to exploit plastid transformation for transplanting better versions of the photosynthetic CO2-fixing enzyme, Rubisco, into plants to improve their growth efficiency in terms of water, fertiliser and light use.Read moreRead less
Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the ....Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the controlled release of therapeutic compounds. The involvement of Honours and Ph.D students in this project will expose the next generation of Australian scientists to this emerging discipline. International collaboration leading to publications in high impact scientific journals will enhance Australia's scientific reputation.Read moreRead less
Practical strategies for engineering the CO2-fixing enzyme, Rubisco, whose subunits are encoded in different subcellular compartments. My recent replacement of the plant CO2-fixing enzyme, Rubisco, with a less efficient bacterial version, with a single type of subunit encoded by a single gene, demonstrated the feasibility of replacing Rubisco. This encourages ongoing attempts to replace plant Rubisco with more efficient versions that would allow the plants to grow with less water, fertiliser or ....Practical strategies for engineering the CO2-fixing enzyme, Rubisco, whose subunits are encoded in different subcellular compartments. My recent replacement of the plant CO2-fixing enzyme, Rubisco, with a less efficient bacterial version, with a single type of subunit encoded by a single gene, demonstrated the feasibility of replacing Rubisco. This encourages ongoing attempts to replace plant Rubisco with more efficient versions that would allow the plants to grow with less water, fertiliser or light. The most efficient Rubiscos are more complex, with two different types of subunits which, in plants, are encoded in different subcellular compartments (nucleus and plastid). This proposal addresses the challenges associated with complementary engineering both genomes to substitute foreign Rubiscos into higher-plant chloroplasts.Read moreRead less
IMPROVING NITROGEN USE EFFICIENCY IN CROP PLANTS: ROLE OF THE AMMONIUM TRANSPORT FAMILY AMT. Improving nitrogen use efficiency in crop plants will reduce the use of environmentally damaging nitrogen fertilisers that threaten through leaching the sustainability of Australia's agricultural sector and local water ecosystems. Plants contain genes that encode transport proteins required for the uptake of nitrogen (ammonium and nitrate) from the soil. We will identify the in planta activity of the A ....IMPROVING NITROGEN USE EFFICIENCY IN CROP PLANTS: ROLE OF THE AMMONIUM TRANSPORT FAMILY AMT. Improving nitrogen use efficiency in crop plants will reduce the use of environmentally damaging nitrogen fertilisers that threaten through leaching the sustainability of Australia's agricultural sector and local water ecosystems. Plants contain genes that encode transport proteins required for the uptake of nitrogen (ammonium and nitrate) from the soil. We will identify the in planta activity of the AMT family of ammonium transporters and associated signalling pathways which control the uptake and assimilation of ammonium in plants. This project will confirm the mechanisms involved in ammonium uptake from the soil and lead to the development of ammonium-nitrogen efficient crop plants.Read moreRead less
Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzy ....Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzyme. This project describes the biochemical characterisation of specific enzyme activities within microcystin synthetase and how they determine the final structure and toxicity of the many forms of microcystin. Interactions between this enzyme complex and its substrate amino acids will provide information for the genetic engineering of this and similar natural products.Read moreRead less
Enhancing Grain Yield Potential and Quality of Lupin. Sustainability of wheat production in Western Australia depends on the continued use of legumes, specifically lupins, in farming systems. The low returns to growers for lupins has jeopardised these sustainable systems. This project aims to gather new information to develop novel genetic strategies to increase yield potential and modify seed composition in lupins, enhancing their commercial worth.
The toxins of water-borne cyanobacteria: regulation and exploitation of their biosynthesis. Water quality is a major concern in Australia, as is the global need for new natural products with antibiotic activity. The mechanisms by which cyanobacteria produce toxins that reduce the quality of water may very well be the answer to the lack of novel medicinal compounds currently being discovered in nature. Encompassed in this one program are the aims of ameliorating the effects of toxic algal blooms ....The toxins of water-borne cyanobacteria: regulation and exploitation of their biosynthesis. Water quality is a major concern in Australia, as is the global need for new natural products with antibiotic activity. The mechanisms by which cyanobacteria produce toxins that reduce the quality of water may very well be the answer to the lack of novel medicinal compounds currently being discovered in nature. Encompassed in this one program are the aims of ameliorating the effects of toxic algal blooms as well as introducing the means for the design and synthesis of a range of novel bioactive products. The benefits include better water quality and biosafety management options, a new generation of drug design and discovery, and the associated transformation of environmental and medical research and education in Australia.Read moreRead less
A sustainable cellular factory for the production of antibiotics by photosynthetic bacteria. The range and rate of natural product discovery is the limiting factor in developing new pharmaceuticals. Traditional methods for the screening of these compounds or for their chemical synthesis are rapidly becoming inadequate as an increasing number of specific therapies, for cancers and infectious diseases for instance, are required. The research proposed will enable the design and production of "unnat ....A sustainable cellular factory for the production of antibiotics by photosynthetic bacteria. The range and rate of natural product discovery is the limiting factor in developing new pharmaceuticals. Traditional methods for the screening of these compounds or for their chemical synthesis are rapidly becoming inadequate as an increasing number of specific therapies, for cancers and infectious diseases for instance, are required. The research proposed will enable the design and production of "unnatural" products, including novel antibiotics, via combinatorial biosynthesis in photosynthetic microorgansims. The outcomes include graduate student training and Australian innovation in an enormous global market that is awaiting the next generation of medicines and associated pharmaceutical production technologies.Read moreRead less
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. Read moreRead less
Clean fuels for the future: Scale up and optimisation of microalgal oil production and biodiesel synthesis. The development of renewable carbon-neutral fuels is an urgent challenge facing our society. This project aims to develop an innovative system for biodiesel production from local Australian algae species. If cultivated under the right conditions, microalgae are very efficient near-continuous producers of biodiesel and are likely the only renewable source of fuel that could match our curren ....Clean fuels for the future: Scale up and optimisation of microalgal oil production and biodiesel synthesis. The development of renewable carbon-neutral fuels is an urgent challenge facing our society. This project aims to develop an innovative system for biodiesel production from local Australian algae species. If cultivated under the right conditions, microalgae are very efficient near-continuous producers of biodiesel and are likely the only renewable source of fuel that could match our current and future demand without competing for arable land and food production. Such systems couple the national/community benefits of energy generation, carbon-capture, biodiesel production and the clean-up of wastewater. Successful outcomes from this project will bring this innovative technology closer to commercial reality. Read moreRead less