Characterisation of vital carbohydrate synthases in pathogenic oomycetes. This project aims to understand the mechanisms that control cell wall stability in the fish pathogen, Saprolegnia parasitica. The biochemical properties and function of vital enzymes involved in cell wall biosynthesis will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology, and structural biology. Next generation ion mobility mass spectrometry will be used to solve challe ....Characterisation of vital carbohydrate synthases in pathogenic oomycetes. This project aims to understand the mechanisms that control cell wall stability in the fish pathogen, Saprolegnia parasitica. The biochemical properties and function of vital enzymes involved in cell wall biosynthesis will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology, and structural biology. Next generation ion mobility mass spectrometry will be used to solve challenging structural questions that cannot be tackled with conventional techniques. Expected outcomes include new knowledge on challenging membrane proteins that allows development of novel strategies for disease control in aquaculture. The data may also be applicable to crop protection from related plant pathogens.Read moreRead less
Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contrib ....Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contribute to our basic knowledge of these processes, provide invaluable information about the specific genes and proteins involved, and provide direct information about the therapeutic potential of specific drugs or inhibitors designed to target this oxygen response in human disease.Read moreRead less
Unravelling cell wall polysaccharide biosynthesis in pathogenic zygomycetes. This project aims to define mechanisms that control cell wall composition and stability in Rhizopus oryzae, a zygomycete fungus responsible for life-threatening human infections. The biochemical properties and function of vital enzymes involved in a newly discovered cell wall polysaccharide biosynthetic pathway will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology an ....Unravelling cell wall polysaccharide biosynthesis in pathogenic zygomycetes. This project aims to define mechanisms that control cell wall composition and stability in Rhizopus oryzae, a zygomycete fungus responsible for life-threatening human infections. The biochemical properties and function of vital enzymes involved in a newly discovered cell wall polysaccharide biosynthetic pathway will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology and structural biology. Expected outcomes include new knowledge on the enzymes that synthesise major fucose-based carbohydrates, to guide the future development of novel strategies for antifungal therapies. The data will also be applicable to animal protection from related zygomycete pathogens.
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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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Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ra ....Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ray diffraction; (ii) To use affinity-labelling to determine the amino acid residues in the binding site of the enzyme's allosteric activator, acetyl-CoA; (iii) To construct chimeric enzymes from different species to define regions of the enzyme which affect its responses to its important allosteric activator, acetyl-CoA.
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Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less
Re-purposing shelved 'antibiotics' in the search for new herbicides. This project aims to identify target-specific herbicidal compounds that inhibit amino acid biosynthesis pathways to tackle herbicide resistance. This project expects to validate a novel herbicide discovery strategy by exploiting the similarity between bacterial and plant enzymes in these pathways to re-purpose failed 'antibiotics'. Expected outcomes include advances in our knowledge of the structure, function and inhibition of ....Re-purposing shelved 'antibiotics' in the search for new herbicides. This project aims to identify target-specific herbicidal compounds that inhibit amino acid biosynthesis pathways to tackle herbicide resistance. This project expects to validate a novel herbicide discovery strategy by exploiting the similarity between bacterial and plant enzymes in these pathways to re-purpose failed 'antibiotics'. Expected outcomes include advances in our knowledge of the structure, function and inhibition of novel herbicide targets, and the identification of compounds with herbicidal activity. This should lay the foundations for long-term benefits related to improving the quantity and quality of Australia’s crops to ensure our food security.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100806
Funder
Australian Research Council
Funding Amount
$419,854.00
Summary
Towards herbicide cocktails with a new mode of action to avert resistance. This project aims to target herbicide resistant weeds which represent one of the largest threats to Australian and global food security. Targeting of unexplored pathways in plants to develop a novel herbicide strategy is expected to be achieved, and will include the structural and functional characterisation of key enzymes in these pathways. This project is expected to provide significant benefits for effective weed manag ....Towards herbicide cocktails with a new mode of action to avert resistance. This project aims to target herbicide resistant weeds which represent one of the largest threats to Australian and global food security. Targeting of unexplored pathways in plants to develop a novel herbicide strategy is expected to be achieved, and will include the structural and functional characterisation of key enzymes in these pathways. This project is expected to provide significant benefits for effective weed management to sustain Australia’s agricultural industry through enhanced food production from increased crop yields, whilst ensuring food security. These outcomes, coupled with decades of over-reliance on current herbicides, means there has never been a greater need for new and effective herbicides.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100181
Funder
Australian Research Council
Funding Amount
$650,000.00
Summary
Strengthening merit-based access and support at the new National Computing Infrastructure petascale supercomputing facility. World-leading high-performance computing is fundamental to Australia's international research success. This facility will provide access to the new National Computational Infrastructure facility by world-leading researchers from six research universities, and sustain ground-breaking work in an increasingly competitive environment.