Indoleamine 2,3-dioxygenase-2: a newly discovered enzyme with a key role in kidney function. We have discovered an enzyme, IDO2, that metabolises the amino acid tryptophan. The enzyme is found in kidney tubule cells and we propose that IDO2 activity regulates sodium reabsorption by the renal tubular cells. Regulation of sodium balance is important for determining blood pressure in health and disease.
Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) ....Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) and to play a role in the regulation of hemoglobin production. We now seek to understand the nature of this interaction at a molecular level and mechanistic level.Read moreRead less
Biomimetic Insights from Enamel: A Nano-mechanical and Nano-structural Investigation of a Natural Ceramic-like Biocomposite. Enamel is a naturally developed example of an optimised material structure that constitutes the hardest tissue in the human body. In addition it is exposed to severe mechanical and environmental challenges and must last the lifetime of the individual and unlike other tissue is unable to heal or repair itself. Understanding the factors controlling the amazing mechanical pr ....Biomimetic Insights from Enamel: A Nano-mechanical and Nano-structural Investigation of a Natural Ceramic-like Biocomposite. Enamel is a naturally developed example of an optimised material structure that constitutes the hardest tissue in the human body. In addition it is exposed to severe mechanical and environmental challenges and must last the lifetime of the individual and unlike other tissue is unable to heal or repair itself. Understanding the factors controlling the amazing mechanical properties of this tissue will be of great benefit for the design of bio-inspired materials and be important for the development of advanced materials for which Australia already has an enviable reputation.Read moreRead less
A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as ....A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as spores. This layer is critical for fungal growth and reproduction and confers water resistance and tolerance to harsh conditions. Our work seeks to develop reagents that can specifically block regions on the protein that are responsible for forming this coating.
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Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding ....Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding protein domains with the goal of selectively blocking these inappropriate interactions. Additionally, these engineered proteins have potential uses as biochemical tools such as to help delineate the functions of natural proteins with no known functions.Read moreRead less
Development and application of new peptide ligation methods for the synthesis and structure-function studies of glycoproteins. Novel synthetic technologies will be developed in this project to facilitate the preparation of glycoproteins, which are of widespread biological and therapeutic interest. These methods will enable the preparation of pure glycoproteins for detailed biochemical and functional studies eventually leading to therapeutic and diagnostic applications.
Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting ....Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting. Underpinned by the ability to access synthetic sulfoproteins, expected outcomes include a detailed understanding of how tyrosine sulfation can modulate function and stability of antibodies and proteins with anticoagulant and anti-inflammatory activities. Significant benefits of the project will include breakthrough technologies for the preparation of homogeneously modified proteins, which will strengthen Australia’s growing biotechnology sector.Read moreRead less
Antimicrobial peptides and immunological protection in a developing mammal. This project offers the opportunity to deliver both economic and scientific benefits, both in the isolation of novel antimicrobials and in positioning Australia's native fauna as important, unique biomedical research models. Antimicrobial peptides offer a solution to the current pressing problem of microbial resistance to antibiotics. This project seeks to isolate such compounds from a previously uninvestigated source, u ....Antimicrobial peptides and immunological protection in a developing mammal. This project offers the opportunity to deliver both economic and scientific benefits, both in the isolation of novel antimicrobials and in positioning Australia's native fauna as important, unique biomedical research models. Antimicrobial peptides offer a solution to the current pressing problem of microbial resistance to antibiotics. This project seeks to isolate such compounds from a previously uninvestigated source, unique to Australia. This project will provide a new perspective on the role of innate protection in a developing mammal, with possible human applications.Read moreRead less
The regulation of gene expression by post-translational modification of transcription factors. Different cells in the body express different subsets of our genes, and it is not well understood how cells know which genes to switch on and which to switch off in a given situation. We will investigate the way in which chemical tags are put onto and removed from the molecules that control gene expression in order to direct their function.
New methods for the chemical synthesis of a library of glycopeptide-based tri-component cancer vaccines. A novel method for the synthesis of tumour-associated glycopeptides will be developed in this research as well as the preparation of a library of glycopeptide-based cancer vaccines. These vaccines will be tested in immunological studies with a view to elucidating new immune-based therapies for the treatment of cancer.