Understanding the molecular basis of heparanase activity. This project aims to advance our understanding of the structure and impact on biological processes of heparanase (HSPE), an enzyme of critical importance. HSPE’s ability to interact with heparan sulfate (HS), a key component of the extracellular matrix and basement membranes, makes HPSE a pivotal enzyme in many important physiological and disease-related processes ranging from angiogenesis, tumour metastasis, inflammation, hair follicle ....Understanding the molecular basis of heparanase activity. This project aims to advance our understanding of the structure and impact on biological processes of heparanase (HSPE), an enzyme of critical importance. HSPE’s ability to interact with heparan sulfate (HS), a key component of the extracellular matrix and basement membranes, makes HPSE a pivotal enzyme in many important physiological and disease-related processes ranging from angiogenesis, tumour metastasis, inflammation, hair follicle development to wrinkle formation. The knowledge gained through this project is expected to provide new insight into the interaction between HSPE and HS/HSPG to reveal new pathways to the development of inhibitors to treat diseases such as cancer and diabetes.Read moreRead less
Discovery and characterisation of novel spider-venom peptides targeting the human sodium ion channel Nav1.7. Drugs that selectively block the human sodium ion channel Nav1.7 are likely to be powerful analgesics for treating a wide variety of pain conditions. However, it has proved difficult to obtain selective blockers of this channel. The aim of this project is to determine whether spider-venoms might provide a source of highly selective Nav1.7 blockers.
Tailoring cellulose properties by manipulating cellulose synthase. Cellulose, a highly abundant polymer produced by plants, has many existing uses in Australian fibre and polymer industries and potential uses as, for example, an abundant feedstuff for biomass conversion into ethanol and other high value products. The optimal properties for different applications vary so that, for example, high crystallinity cellulose gives strong fibres whereas low crystallinity cellulose dissolves in gentler so ....Tailoring cellulose properties by manipulating cellulose synthase. Cellulose, a highly abundant polymer produced by plants, has many existing uses in Australian fibre and polymer industries and potential uses as, for example, an abundant feedstuff for biomass conversion into ethanol and other high value products. The optimal properties for different applications vary so that, for example, high crystallinity cellulose gives strong fibres whereas low crystallinity cellulose dissolves in gentler solvents on the way to producing cellulose-based polymers. By exploring ways to adjust the properties of celluloses for use in different applications, we can deliver potential benefits to primary producers, industries and the environment.
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Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplo ....Discovery of new genes for plant cellulose biosynthesis and improved fibre production. Cellulose, the world's most abundant biopolymer, is important to the cotton and forest industries and for human and animal nutrition. Before biotechnology can manipulate cellulose, we must identify the enzymes of the synthesis pathway and understand how their properties determine the properties of the cellulose they produce. Not all enzymes are known and any relationships to cellulose properties remain unexplored. This study extends our successful mutational analysis of cellulose synthesis in Arabidopsis and initiates the molecular analysis of organisms making cellulose with distinctive properties. It will significantly advance knowledge of cellulose biosynthesis and identify novel genes for fibre improvement.Read moreRead less
Novel strategies in the design and development of antivirals against dengue virus. Globally, there are 50-100 million cases of dengue fever, with 500,000 cases of the more severe dengue haemorrhagic fever, each year. Australia has between 100 and 900 cases of dengue infection annually, often from travellers, but disease outbreaks occur in northern Australia. Effective anti-viral treatment will reduce disease burden. The project contributes to an evidence-based drug design program in collaboratio ....Novel strategies in the design and development of antivirals against dengue virus. Globally, there are 50-100 million cases of dengue fever, with 500,000 cases of the more severe dengue haemorrhagic fever, each year. Australia has between 100 and 900 cases of dengue infection annually, often from travellers, but disease outbreaks occur in northern Australia. Effective anti-viral treatment will reduce disease burden. The project contributes to an evidence-based drug design program in collaboration with Australia's leading biotechnology industries. As a biotechnology industry project developing treatments for an emerging disease, it contributes to the national research priorities of Frontier technologies for building and transforming Australian industries, Promoting and maintaining good health and Safeguarding Australia.Read moreRead less
The development of mass spectrometry techniques for mapping post-translational modifications in the wheat pathogen Stagonospora nodorum. The fungus Stagonospora nodorum is a significant pathogen of wheat causing in excess of $100 million dollars in yield losses per annum in Australia. This project will develop new analytical methods that can be used to detect important protein modifications in Stagonospora nodorum with the goal of securing Australia's wheat supply.
An Open Source Approach to Understanding an Important Parasite Ion Pump. This project plans to synthesise new compounds that bind the protein ATP4, an essential ion pump in the malaria parasite. It plans to generate a three-dimensional map to understand how these compounds stop ATP4 from working. Several promising new medicines for malaria target ATP4, yet we do not understand properly how they do so. The project’s intended aims will be achieved using new methods in synthetic chemistry and membr ....An Open Source Approach to Understanding an Important Parasite Ion Pump. This project plans to synthesise new compounds that bind the protein ATP4, an essential ion pump in the malaria parasite. It plans to generate a three-dimensional map to understand how these compounds stop ATP4 from working. Several promising new medicines for malaria target ATP4, yet we do not understand properly how they do so. The project’s intended aims will be achieved using new methods in synthetic chemistry and membrane biology, and by leveraging global scientific inputs through online research methods allowing anyone to participate.Read moreRead less
The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals ....The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals and attack by the immune system. We will discover and characterise the molecular basis for cyst wall formation. This fundamental knowledge will be the building block for new, highly specific drugs and vaccines to control these extremely important pathogens.Read moreRead less
Imaging the world of miniature venomous arthropods. Venomous arthropods produce a myriad of biologically active peptides, with many having potential as pharmacological tools, bioinsecticides and pharmaceuticals. Most studies to date have focussed on large arthropods; smaller species remain neglected due to the difficulties of venom collection. This project seeks to further advance the pioneering imaging mass spectrometry approaches the project team developed for imaging toxins in the venom gland ....Imaging the world of miniature venomous arthropods. Venomous arthropods produce a myriad of biologically active peptides, with many having potential as pharmacological tools, bioinsecticides and pharmaceuticals. Most studies to date have focussed on large arthropods; smaller species remain neglected due to the difficulties of venom collection. This project seeks to further advance the pioneering imaging mass spectrometry approaches the project team developed for imaging toxins in the venom glands of spiders and centipedes. By combining high-resolution matrix-assisted laser desorption ionisation imaging data with histological and transcriptomic information the project aims to provide the first detailed insights into the neglected world of miniature arthropod venoms. The approaches developed by this project aim to have wide application in the field of biology.Read moreRead less
The role of the Ttyh1 protein in cell activation. We have cloned TTYH1, a human homologue of the Drosophila melanogaster tweety gene. The mouse gene has also been identified. The predicted structure of the protein is a membrane protein with 5 transmembrane domains. We have also expressed a GFP-tagged fusion protein in mouse fibroblasts. Confocal microscopy indicates that this protein is likely to be a novel adhesion molecule, with a cellular distribution characteristic of molecules such as integ ....The role of the Ttyh1 protein in cell activation. We have cloned TTYH1, a human homologue of the Drosophila melanogaster tweety gene. The mouse gene has also been identified. The predicted structure of the protein is a membrane protein with 5 transmembrane domains. We have also expressed a GFP-tagged fusion protein in mouse fibroblasts. Confocal microscopy indicates that this protein is likely to be a novel adhesion molecule, with a cellular distribution characteristic of molecules such as integrins. We aim to determine the function of Ttyh1, its interacting intra- and extra-cellular proteins and to assess its candidature as a molecule of importance in cell migration and adhesion.Read moreRead less