A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We hav ....A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We have shown that Neurospora, like other less tractable multicellular eukaryotes, is tolerant of sequence mismatch, allowing high resolution analysis of individual recombination events. This project will build on fundamental advances we have already made in understanding how recombination occurs.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
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
New biocatalysts for selective chemical oxidations under extreme conditions. This project will identify and design new enzyme biocatalysts which function under extreme conditions such as elevated temperature and high concentrations of peroxides. These enzymes will be sourced from microorganisms which are located in extreme biological environments e.g. hot springs (the so-called extremophiles). The expected outcome of this project are the identification of robust enzymes which can catalyse select ....New biocatalysts for selective chemical oxidations under extreme conditions. This project will identify and design new enzyme biocatalysts which function under extreme conditions such as elevated temperature and high concentrations of peroxides. These enzymes will be sourced from microorganisms which are located in extreme biological environments e.g. hot springs (the so-called extremophiles). The expected outcome of this project are the identification of robust enzymes which can catalyse selective oxidation reactions in complex organic molecules, such as steroids. The new biocatalysts developed in this project will have significant benefit in the development of new routes to access bespoke molecules of value in fine chemical synthesis and drug development.
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New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
Th ....New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
This project, which will use cutting edge techniques in an experimental model, seeks to characterise this important enzyme's function so that better treatments can be developed in future for diabetes and obesity.
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Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Pair bonding: is it all in the brain? This project aims to understand the interaction between classic pair bonding neural circuits, parasites, and the immune system in sleepy lizards. Social bonds are a cornerstone of human societies, especially true of the pair bond and this project expects to generate knowledge to help understand why healthy adult pair bonds are the single best predictor of longevity in humans. The expected outcomes of this project are to reveal the mechanistic basis of pair b ....Pair bonding: is it all in the brain? This project aims to understand the interaction between classic pair bonding neural circuits, parasites, and the immune system in sleepy lizards. Social bonds are a cornerstone of human societies, especially true of the pair bond and this project expects to generate knowledge to help understand why healthy adult pair bonds are the single best predictor of longevity in humans. The expected outcomes of this project are to reveal the mechanistic basis of pair bonding by identifying the brain regions, cell types and neurochemicals that promote pair bonding behaviour — for the first time in a wild animal. This project should provide significant benefits by increasing our knowledge of how pair bonds promote wellness.Read moreRead less
Synthetic phenazines for enhanced biogas production from renewable and non-renewable resources. Methane (biogas) has a large role to play in meeting the energy needs of the human race globally whilst reducing greenhouse gas emissions. Microbial communities are responsible for biogas production from non-renewable (coal) and renewable (food waste) resources. This project seeks to: increase biogas yields by redirecting electron flow towards biogas producing microbes using electrochemically active p ....Synthetic phenazines for enhanced biogas production from renewable and non-renewable resources. Methane (biogas) has a large role to play in meeting the energy needs of the human race globally whilst reducing greenhouse gas emissions. Microbial communities are responsible for biogas production from non-renewable (coal) and renewable (food waste) resources. This project seeks to: increase biogas yields by redirecting electron flow towards biogas producing microbes using electrochemically active phenazines; understand the molecular mechanism by which phenazines increase biogas yields; and, assess the environmental consequence of phenazine application to coal seam gas production and anaerobic digestion of food waste. Phenazines are likely to emerge as a safe and cost-effective technology for improved biogas generation.Read moreRead less
A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less