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
Enzymatic synthesis, microencapsulation and biological evaluation of a new class of omega-3 derived functional food ingredients. Inflammatory mediated diseases such as cardiovascular disease, type-2 diabetes, metabolic syndrome and Alzheimer's disease are major causes of death in Australia. Rates of these diseases are rising over time, partly due to poor diet including low consumption levels of healthy omega-3 fatty acids from fish. This project aims to develop healthy food ingredients from natu ....Enzymatic synthesis, microencapsulation and biological evaluation of a new class of omega-3 derived functional food ingredients. Inflammatory mediated diseases such as cardiovascular disease, type-2 diabetes, metabolic syndrome and Alzheimer's disease are major causes of death in Australia. Rates of these diseases are rising over time, partly due to poor diet including low consumption levels of healthy omega-3 fatty acids from fish. This project aims to develop healthy food ingredients from naturally occurring omega-3 fatty acid derivatives that are more stable to oxidation and more biologically active than fish derived omega-3 fatty acids. The development of these omega-3 derivatives as functional food ingredients could provide an additional strategy for helping to prevent the rapid increase in inflammatory mediated diseases in the Australian population.Read moreRead less
The mechanisms and roles of receptor clustering in cell activation and wound healing by growth factors. Growth factors regulate cell proliferation, migration and differentation by interaction with receptors. Such receptors are usually localized at the cell surface, and require intracellular transduction systems to transmit the signal to the cell interior. We have recently shown the hormone-induced clustering of heterologous hormone receptors in cells, and that this occurs with the co-clustering ....The mechanisms and roles of receptor clustering in cell activation and wound healing by growth factors. Growth factors regulate cell proliferation, migration and differentation by interaction with receptors. Such receptors are usually localized at the cell surface, and require intracellular transduction systems to transmit the signal to the cell interior. We have recently shown the hormone-induced clustering of heterologous hormone receptors in cells, and that this occurs with the co-clustering of downstream signalling molecules at sites of engagement with the extracellular matrix. In addition, we have found that cells presented with an extracellular matrix respond better to subsequent growth factor stimulation. The project aims to determine the cellular mechanisms underlying receptor clustering and the basis of the receptor-extracellular matrix interaction. This will enhance our understanding of growth factor function in a number of conditions, including wound healing. We will extend our in vitro results to the animal model to define parameters for enhanced wound repair.Read moreRead less
Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.
Predicting Drug-drug Interactions Due To Tyrosine Kinase Inhibitors: Inhibition Of Drug Metabolising Enzymes And Transporters
Funder
National Health and Medical Research Council
Funding Amount
$535,495.00
Summary
Tyrosine kinase inhibitors (TKIs) are a new class of anticancer agents. Cancer patients typically receive multiple drugs, for the treatment of cancer and other diseases, increasing the probability of interactions between coadministered drugs. Despite the widespread use of TKIs, their potential to cause drug interactions is poorly understood. Using novel in vitro approaches, this project will identify drug interactions precipitated by TKIs thereby improving drug efficacy and patient safety.
Exploiting novel yeast attributes to produce industrial strains with better fermentative and processing qualities. Food and beverage fermentations are problematic processes, largely due to limitations of the yeast being used. This laboratory has indentified in individual yeast strains highly desirable fermentative characteristics or else the ability to over-produce compounds that benefit product processing. Pursuing the commercial potential of these findings is the specific objective of this pro ....Exploiting novel yeast attributes to produce industrial strains with better fermentative and processing qualities. Food and beverage fermentations are problematic processes, largely due to limitations of the yeast being used. This laboratory has indentified in individual yeast strains highly desirable fermentative characteristics or else the ability to over-produce compounds that benefit product processing. Pursuing the commercial potential of these findings is the specific objective of this proposal. Thus we will extend our collaboration with Coopers Brewery through this new project area with the aims of a) producing optimised, hybrid (non-GMO) strains with combinations of desirable fermentation properties, b) develop novel processing or quality-enhancing treatments while c) generating a high caliber PhD graduate with extensive industry experience.Read moreRead less
Role of alanine aminotransferase in improved nitrogen use efficiency (NUE) in cereals. The use of nitrogen-based fertilisers by crop plants is poor where efficiencies (nitrogen taken up to that applied) is often less than 40%. Nitrogen not used is often lost to the environment through leaching and or volatilisation. Improving nitrogen use efficiency (NUE) in agriculture will decrease overall nitrogen fertiliser use and minimise its environmental footprint. This project will characterise a nov ....Role of alanine aminotransferase in improved nitrogen use efficiency (NUE) in cereals. The use of nitrogen-based fertilisers by crop plants is poor where efficiencies (nitrogen taken up to that applied) is often less than 40%. Nitrogen not used is often lost to the environment through leaching and or volatilisation. Improving nitrogen use efficiency (NUE) in agriculture will decrease overall nitrogen fertiliser use and minimise its environmental footprint. This project will characterise a novel NUE technology that when transferred to plants significantly improves NUE. We will define the phenotype at the molecular, biochemical and physiological levels to maximise its adoption to other agricultural crops such as wheat, barley and maize.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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