Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the ....Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the passage of cells through the cell cycle so that repair can occur. This project studies the mechanism of action of one of these enzymes which will be of benefit in designing new compounds to fight disease. Read moreRead less
Novel mechanisms of bacterial arsenic metabolism - arsenate reduction and arsenite oxidation. Novel arsenic metabolising bacteria (i.e., arsenate respiring and arsenite oxidising), which are both phylogenetically and physiologically unique, have been isolated from arsenic-contaminated areas in Australia. The arsenate respiring bacterium, Chrysiogenes arsenatis, is of particular interest as it is the only organism reported able to respire with arsenate using the respiratory substrate acetate as t ....Novel mechanisms of bacterial arsenic metabolism - arsenate reduction and arsenite oxidation. Novel arsenic metabolising bacteria (i.e., arsenate respiring and arsenite oxidising), which are both phylogenetically and physiologically unique, have been isolated from arsenic-contaminated areas in Australia. The arsenate respiring bacterium, Chrysiogenes arsenatis, is of particular interest as it is the only organism reported able to respire with arsenate using the respiratory substrate acetate as the electron donor. It is proposed that physiological, biochemical and molecular biological studies be carried out to better understand the mechanisms by which these organisms metabolise arsenic. The knowledge gained from these studies will have worldwide application in the development of an arsenic bioremediation system.Read moreRead less
Feasting on protein? Strategies of organic nitrogen acquisition by plant roots. Crops require large amounts of nitrogen for growth. Application of nitrogen fertiliser enhances yield, but causes off-site nitrogen pollution, a main threat to ecosystem integrity. Most nitrogen in soil occurs as organic complexes that are broken down by soil organism into small compounds, which are taken up roots or lost from the soil. This project will generate fundamental knowledge of how an Australian species and ....Feasting on protein? Strategies of organic nitrogen acquisition by plant roots. Crops require large amounts of nitrogen for growth. Application of nitrogen fertiliser enhances yield, but causes off-site nitrogen pollution, a main threat to ecosystem integrity. Most nitrogen in soil occurs as organic complexes that are broken down by soil organism into small compounds, which are taken up roots or lost from the soil. This project will generate fundamental knowledge of how an Australian species and a crop species with unusual root specialisations access soil organic nitrogen, thus increasing the efficiency of nitrogen use and reducing nitrogen loss. The research employs cutting-edge techniques for sustainable resource use, improved efficiency of crops and farming systems, and preservation of Australia's biodiversity.Read moreRead less
A Unique Target in the Purine Biosynthesis of the Pathogen Helicobacter pylori. The uptake systems of purine and analogues of the human pathogen Helicobacter pylori will be characterised because they can be utilised to introduce cytotoxic compounds into the cells. The first step in de novo purine biosynthesis of the bacterium is catalysed by two different enzymes, which are components of other biosynthetic pathways. These unique properties make them excellent potential therapeutic targets. Their ....A Unique Target in the Purine Biosynthesis of the Pathogen Helicobacter pylori. The uptake systems of purine and analogues of the human pathogen Helicobacter pylori will be characterised because they can be utilised to introduce cytotoxic compounds into the cells. The first step in de novo purine biosynthesis of the bacterium is catalysed by two different enzymes, which are components of other biosynthetic pathways. These unique properties make them excellent potential therapeutic targets. Their individual combined activities in purine biosynthesis will be characterised in situ and in vitro. Isogenic mutants with inactivated genes encoding for these enzymes will be constructed to investigate their role in the survival of the organism.Read moreRead less
Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein function ....Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein functions. By doing so, the project will illuminate how haem oxygenase-1 alters cell functions in a beneficial way. This information will eventually assist in preventing the serious disorders associated with deficiency of haem oxygenase-1. It will also provide the basis for novel treatments to slow down age-associated diseases.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561013
Funder
Australian Research Council
Funding Amount
$220,000.00
Summary
X-ray diffraction System for Protein Crystallography and Structural Biology. Knowledge of protein structures enables researchers to explain cellular function at a molecular level. In particular, it provides essential information to understand the mechanism of diseases, such as cancer or AIDS, and it ultimately leads to the design of better drugs.
An in-house X-ray protein crystallography facility will allow us to determine the structures of key proteins effectively and competitively, opening up ....X-ray diffraction System for Protein Crystallography and Structural Biology. Knowledge of protein structures enables researchers to explain cellular function at a molecular level. In particular, it provides essential information to understand the mechanism of diseases, such as cancer or AIDS, and it ultimately leads to the design of better drugs.
An in-house X-ray protein crystallography facility will allow us to determine the structures of key proteins effectively and competitively, opening up extensive possibilities for multi-disciplinary ground-breaking research.
The University research portfolio has evolved to embrace the revolution in structural biology with numerous projects and collaborations focusing on proteins involved in bacterial infections, degenerative disorders and biotechnological applications.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
The development of tools to study carbohydrate-processing enzymes implicated in human disease. Diseases caused by improper function of carbohydrate-processing enzymes are a major health burden. This research aims to find ways to restore the function of these enzymes bringing a better quality of life to people suffering from these diseases.
Understanding and exploiting bacterial sulfatases. Bacterial sulfatases participate in environmental nutrient cycling and are implicated in bacterial pathogenesis mechanisms. These enzymes catalyze the hydrolysis of sulfate esters and possess an unusual posttranslational active-site modification where a cysteine residue is oxidized to formylglycine. We will study the mechanism of these enzymes in detail and design inhibitors that exploit the reactivity of this aminoacid. This work has significan ....Understanding and exploiting bacterial sulfatases. Bacterial sulfatases participate in environmental nutrient cycling and are implicated in bacterial pathogenesis mechanisms. These enzymes catalyze the hydrolysis of sulfate esters and possess an unusual posttranslational active-site modification where a cysteine residue is oxidized to formylglycine. We will study the mechanism of these enzymes in detail and design inhibitors that exploit the reactivity of this aminoacid. This work has significance because of application to areas that include the treatment of cancer and bacterial infections. Additionally, we will clone novel carbohydrate sulfatases from the heparin-degrading bacterium Flavobacterium heparinum. These sulfatases will have use in biotechnology for characterization of sulfated glycoconjugates.Read moreRead less