Probing the four photosynthetic membrane protein complexes at work in situ in leaves. This proposal aims at sustainable improvements in plant productivity and photosynthetic adaptation in drastic Australian climates. In photosynthesis, membranes with the four multiprotein complexes use sunlight to make compounds that drive carbon assimilation. Instead of the usual dissection of photosynthetic membranes, this project will develop and refine the applicant's rapid, reliable, non-intrusive technique ....Probing the four photosynthetic membrane protein complexes at work in situ in leaves. This proposal aims at sustainable improvements in plant productivity and photosynthetic adaptation in drastic Australian climates. In photosynthesis, membranes with the four multiprotein complexes use sunlight to make compounds that drive carbon assimilation. Instead of the usual dissection of photosynthetic membranes, this project will develop and refine the applicant's rapid, reliable, non-intrusive techniques to probe the four membrane complexes at work in their native state in leaves. Two portable commercial instruments will potentially emerge from the techniques. This novel non-reductionist approach will identify key limitations to photosynthetic performance under stress, and insights into improvements for primary plant productivity.Read moreRead less
Biosynthesis and functions of two phytotoxins in Septoria nodorum blotch. This project aims to investigate how a fungal plant pathogen makes and uses small bioactive molecules to facilitate infection. It will characterise the function of the genes and enzymes involved in the biosynthesis of a light-activated phytotoxic molecule and a potential anti-plant defence molecule found in the pathogenic wheat fungus Parastagonospora nodorum, and investigate their contribution to disease development. Expe ....Biosynthesis and functions of two phytotoxins in Septoria nodorum blotch. This project aims to investigate how a fungal plant pathogen makes and uses small bioactive molecules to facilitate infection. It will characterise the function of the genes and enzymes involved in the biosynthesis of a light-activated phytotoxic molecule and a potential anti-plant defence molecule found in the pathogenic wheat fungus Parastagonospora nodorum, and investigate their contribution to disease development. Expected outcomes include better understanding of plant-microbe interactions, disease management strategies, technologies for identifying biosynthetic pathways in other fungi, and enzyme technology for synthesising molecules. This could lead to new herbicides, biopesticides and drugs.Read moreRead less
The cellulose synthase complex of the Arabidopsis primary cell wall. The polysaccharide cellulose is the basis for the wood and cotton fibre industries of Australia and much of our research on the mechanism of synthesis has been supported by those industries over the past decade. The present project focuses on the proteins making cellulose and how they organised into functional complexes that are able to make cellulose. The knowledge it provides, together with that from other projects, will move ....The cellulose synthase complex of the Arabidopsis primary cell wall. The polysaccharide cellulose is the basis for the wood and cotton fibre industries of Australia and much of our research on the mechanism of synthesis has been supported by those industries over the past decade. The present project focuses on the proteins making cellulose and how they organised into functional complexes that are able to make cellulose. The knowledge it provides, together with that from other projects, will move us towards the situation where we can manipulate the rate at which cellulose is produced and change its detailed properties. This opens the way to industry producing fibres with more desirable properties and producing novel cellulose-based materials tailored to specific applications.Read moreRead less
Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology t ....Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets is mandated by humanity, and also to safeguard Australia's region against the social and economical implication of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors ....Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors, agonists and antagonists to override and bypass the chemical control mechanisms through which hormone levels are usually maintained at homeostasis. The research is expected to lead to a better fundamental understanding of hormone metabolism, and to underpin the basis for the development of new disease therapies.Read moreRead less
Facilitating drug synthesis, development and detection: the enzymatic synthesis of beta-glucuronides. This project will develop new catalysts to aid the development of pharmaceuticals and help fight the war against drugs.
New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bact ....New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bacterial and viral infections, neuro-degenerative conditions and impaired cognitive function. Anti-angiogenic compounds that control otherwise unregulated cellular growth may also arise from these studies. The generation of new, homochiral metabolites for use in chemoenzymatic synthesis should also emerge from this project.Read moreRead less
Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically ....Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically active systems, especially pharmaceutically or agrochemically valuable natural products and relevant analogues.Read moreRead less
Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthes ....Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthesis of both extensive expertise in platelet/cardiovascular research and bioengineering/rheology should provide a substantial platform from which fundamental new discoveries in this niche area can be made. The development of novel platelet analysis tools arising from this work may also ultimately lead to new intellectual property and attract industry based funding.Read moreRead less
Development of potent and specific modulators of the human sodium channel Nav1.7. There are few effective drugs available for the treatment of chronic pain. This team recently discovered that spider venoms are a rich source of inhibitors of Nav1.7, a new target for anti-pain drugs. The goal of this project is to develop potent blockers of Nav1.7 that can be used to critically assess the role of this ion channel in mediating pain.