Investigating the functional interaction between vasopressin and angiotensin receptors. Kidney disease resulting from diabetes is a major health issue for Australians, and indigenous Australians in particular. This project aims to enable improved therapies to be developed, as well as better inform doctors regarding the use of potential combinations of existing pharmaceuticals to treat this condition.
Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also d ....Fish venom as a model system for the molecular evolution of defensive toxins. The key aim of this study is to undertake a thorough investigation of venoms found in distinct fish lineages, including enigmatic species such as venomous and medically important species such as the stonefish. By characterising the biodiversity of toxins found in the venoms of different fish, the evolutionary history of venom in this major vertebrate lineage can be revealed. The investigations proposed here will also determine the functional activities of different venoms and their components. This will not only help the understanding of the medical consequences of the annual thousands of fish envenomings but also explore a largely unstudied resource for the discovery of new pharmacological diagnostics and therapeutics.Read moreRead less
Understanding allosteric modulation and functional selectivity at G Protein-Coupled Receptors (GPCRs). GPCRs are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
Stronger, coarser-grained biodegradable zinc alloys. This project aims to develop stronger and more durable zinc alloys for a new generation of biodegradable metals for potential load-bearing orthopaedic applications. It expects to deliver a group of novel zinc alloys with better properties and a new technology for manufacturing them, and to use advanced experimental techniques to reveal deformation and strengthening mechanisms that underlie the unusual Hall-Petch and anomalous twinning phenomen ....Stronger, coarser-grained biodegradable zinc alloys. This project aims to develop stronger and more durable zinc alloys for a new generation of biodegradable metals for potential load-bearing orthopaedic applications. It expects to deliver a group of novel zinc alloys with better properties and a new technology for manufacturing them, and to use advanced experimental techniques to reveal deformation and strengthening mechanisms that underlie the unusual Hall-Petch and anomalous twinning phenomena and the unprecedented properties of these alloys. Expected outcomes are likely to form the technology and scientific basis for developing better biodegradable metallic alloys. This has the potential eventually to create a better life for thousands of Australian patients.Read moreRead less
Stronger zinc alloys for more flexible biodegradable stents. This project aims to develop stronger zinc alloys for a new class of biodegradable metallic stents. A key challenge for biodegradable stent technology is to make stents as thin as possible while also being strong. This project will develop ultra-high strength zinc alloys that can be used to fabricate thinner biodegradable stents for easier surgical operation. The project outcomes should be a major step in the design and development of ....Stronger zinc alloys for more flexible biodegradable stents. This project aims to develop stronger zinc alloys for a new class of biodegradable metallic stents. A key challenge for biodegradable stent technology is to make stents as thin as possible while also being strong. This project will develop ultra-high strength zinc alloys that can be used to fabricate thinner biodegradable stents for easier surgical operation. The project outcomes should be a major step in the design and development of a new generation of biodegradable stents that will avoid the risks associated with existing products and potentially create a better life for millions of patients worldwide.Read moreRead less
A New Approach to Advanced Steels via Cluster and Precipitate Strengthening. Formation of interphase nanoparticles and clusters is a new approach to increase strength in advanced high strength steels. Exceptionally high strength levels can be achieved in alloys that only have solute clusters by controlling the temperature-time history. However, the exact mechanism for the formation of clusters and precipitates and the cluster strengthening mechanism are not understood, nor do we know how to cont ....A New Approach to Advanced Steels via Cluster and Precipitate Strengthening. Formation of interphase nanoparticles and clusters is a new approach to increase strength in advanced high strength steels. Exceptionally high strength levels can be achieved in alloys that only have solute clusters by controlling the temperature-time history. However, the exact mechanism for the formation of clusters and precipitates and the cluster strengthening mechanism are not understood, nor do we know how to control cluster formation. This project aims to develop a fundamental understanding of the formation of clusters and nanoprecipitates and determine their contribution to strengthening and other mechanical properties using advanced characterisation techniques such as atom probe tomography and electron microscopy.Read moreRead less
Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Advanced high strength steels produced by energy efficient direct strip casting. Over one billion tonnes of steel is produced every year and one method of reducing the environmental footprint of this production is through strip casting. This process reduces the energy required to process liquid steel into thin sheet product by an astounding 90 per cent. This proposal aims to expand the application of this technology to new steel grades.
Allosteric modulators as novel probes of G-Protein coupled receptor function. This research will provide novel mechanistic understanding on the function of one of the largest protein families in the mammalian genome, and the most important family with respect to drug targets. The insights gained thus have direct relevance to drug discovery. The discovery of novel G protein-coupled receptor (GPCR) allosteric enhancers will not only lead to potentially new therapeutic agents, but can significant ....Allosteric modulators as novel probes of G-Protein coupled receptor function. This research will provide novel mechanistic understanding on the function of one of the largest protein families in the mammalian genome, and the most important family with respect to drug targets. The insights gained thus have direct relevance to drug discovery. The discovery of novel G protein-coupled receptor (GPCR) allosteric enhancers will not only lead to potentially new therapeutic agents, but can significantly value-add to other national research efforts focusing on GPCR structural biology.Read moreRead less
Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of rec ....Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of receptor, the project expects to provide significant benefits to the research field by impacting on future drug discovery efforts, not only at mAChRs, but at other structurally related receptors.Read moreRead less