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
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
A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough ....A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough and responsive hydrogel platform from this disordered protein family through greater understanding of structure and mechanical function and incorporating adequate stiffness, strength and biocompatibility. Such tough hydrogels would be applicable to a range of biotechnological applications (eg intervertebral disc repair or artificial skin tissue engineering).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
Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for ....Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for the construction and modification of peptides and proteins by harnessing the energy in a unique class of strained molecules. A focus on peptide-based inhibitors of the proteasome, a critical target for modern cancer treatments, should provide future health and economic benefits for the Australian community.Read moreRead less
Synthetic, Molecular and Biological Studies on Novel Marine Metabolites Isolated from Great Barrier Reef Sponges. Whilst structurally remarkable marine natural products, generated via unprecedented biosynthetic pathways, continue to be isolated from organisms found on the Barrier Reef these substances remain largely unexploited in terms of both their potent biological and ecological properties. Efficient syntheses of two classes of marine metabolites will be undertaken to allow biological, biosy ....Synthetic, Molecular and Biological Studies on Novel Marine Metabolites Isolated from Great Barrier Reef Sponges. Whilst structurally remarkable marine natural products, generated via unprecedented biosynthetic pathways, continue to be isolated from organisms found on the Barrier Reef these substances remain largely unexploited in terms of both their potent biological and ecological properties. Efficient syntheses of two classes of marine metabolites will be undertaken to allow biological, biosynthetic and ecological evaluation of advanced intermediates and final products. Such evaluations will provide new insights into the therapeutic and ecological potential as well as the origins of these natural products. New agents for the management of marine ecosystems and the treatment of oncological and other diseases should emerge.Read moreRead less
The role of gamma glutamyl cyclotransferase in glutathione homeostasis. The aim of this study is to understand the structure and function of gamma-glutamyl cyclotransferase (GGCT) and its role in glutathione synthesis and turnover. Glutathione is essential for life and serves multiple biological functions protecting against oxidative stress, and aiding in the detoxification and excretion of foreign chemicals. This study will explore a new approach to changing intracellular glutathione concentra ....The role of gamma glutamyl cyclotransferase in glutathione homeostasis. The aim of this study is to understand the structure and function of gamma-glutamyl cyclotransferase (GGCT) and its role in glutathione synthesis and turnover. Glutathione is essential for life and serves multiple biological functions protecting against oxidative stress, and aiding in the detoxification and excretion of foreign chemicals. This study will explore a new approach to changing intracellular glutathione concentrations that has wide applications in the treatment of inherited enzyme deficiencies, cancer and the development of herbicide resistant crop plants. The study will also contribute to the training of scientists for the future development of the Australian biotechnology industryRead moreRead less
Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic be ....Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic benefits for the Australian community, including: the first approach to a class of promising antibiotic peptide natural product analogues, the development of a mild electrochemical approach to peptide modification, and the production of a library of novel amino acids for incorporation into potential antibiotic leads.Read moreRead less
Total Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of functional syntheses of Australian natural products and certain analogues of ecological and therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments, reduce the need for removal of organisms from marine environments both within and outside of Australia as well as helping maintain and enhance chemi ....Total Synthesis and Biological Evaluation of Australian Sponge Metabolites. The development of functional syntheses of Australian natural products and certain analogues of ecological and therapeutic significance will emerge. Such activities will lead to the identification and evaluation of molecular entities of value in managing marine environments, reduce the need for removal of organisms from marine environments both within and outside of Australia as well as helping maintain and enhance chemical synthesis capacity within the country. The proposed studies could lead to the identification of related natural products produced by organisms on the Great Barrier Reef and that may display even more potent activities and/or complementary ecological roles.Read moreRead less