A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of the ....A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of these molecules as drug leads. The potential exists for multibillion dollar markets for these new drugs that could provide significant economic benefits to Australia.Read moreRead less
Probing the Tasmanian Devil Serum Proteome for Preclinical Diagnosis of Devil Facial Tumour Disease. The Tasmanian Devil (Sarcophilus harrisii) is a carnivorous marsupial endemic to the island state of Tasmania, and is found all over the state. Over the past decade, a dramatic decline has occurred in the Devil population in association with the emergence of Devil Facial Tumour Disease (DFTD). This project aims to develop a preclinical diagnostic test for DFTD that will provide vital information ....Probing the Tasmanian Devil Serum Proteome for Preclinical Diagnosis of Devil Facial Tumour Disease. The Tasmanian Devil (Sarcophilus harrisii) is a carnivorous marsupial endemic to the island state of Tasmania, and is found all over the state. Over the past decade, a dramatic decline has occurred in the Devil population in association with the emergence of Devil Facial Tumour Disease (DFTD). This project aims to develop a preclinical diagnostic test for DFTD that will provide vital information for use in developing management strategies to ensure the ongoing survival of the Tasmanian Devil. The benefit to Australia in performing this research rests in the new technology that will be developed and the application of this technology to key areas of national and international significance.Read moreRead less
Covalent Hydrogen Bond Mimetics of Helical Peptide Hormones. Peptide hormones have been identified that adopt a helical shape when bound to their receptor. The project will produce new versions of these hormones by the use of directly bonded chemical linkers in place of the relatively weak helix hydrogen bonds. The resulting hormone mimics will be more stable, have lower molecular weight and be more selective than the natural hormones making them more suitable as drugs. Our new chemical techn ....Covalent Hydrogen Bond Mimetics of Helical Peptide Hormones. Peptide hormones have been identified that adopt a helical shape when bound to their receptor. The project will produce new versions of these hormones by the use of directly bonded chemical linkers in place of the relatively weak helix hydrogen bonds. The resulting hormone mimics will be more stable, have lower molecular weight and be more selective than the natural hormones making them more suitable as drugs. Our new chemical techniques allow us for the first time to fully investigate this approach which if successful will be applicable to many other helical peptides and therefore could be an important drug development technique.Read moreRead less
Common hot spots in protein-activated GPCRs enable discovery of new ligands for mapping of G-protein signalling pathways. This project will teach researchers and industry how to more rapidly discover new compounds for development into medicines, and how to design them with reduced side effects. This interdisciplinary research will provide excellent training for scientists in chemistry, pharmacology, biochemistry and biotechnology. It will advance fundamental science at the chemistry-biology inte ....Common hot spots in protein-activated GPCRs enable discovery of new ligands for mapping of G-protein signalling pathways. This project will teach researchers and industry how to more rapidly discover new compounds for development into medicines, and how to design them with reduced side effects. This interdisciplinary research will provide excellent training for scientists in chemistry, pharmacology, biochemistry and biotechnology. It will advance fundamental science at the chemistry-biology interface, attract international interest from researchers, students, and companies, with potential for translational and commercial outcomes. New drug leads and information on how important drug targets communicate with different intracellular signalling pathways has potential to impact on National Research Priorities of good health and building Australian industry.Read moreRead less
Surface Forces in Aqueous Electrolytes. This project studies the force between two nearby colloidal particles or macromolecules in aqueous electrolyte solutions. Although such forces control the approach and binding of particles in electrolytes and hence have large practical significance they are poorly known. In recent work I established a rigorous scheme for calculation of the electrostatic contribution to the force and proved its feasibility. In order to realise practical applications, such a ....Surface Forces in Aqueous Electrolytes. This project studies the force between two nearby colloidal particles or macromolecules in aqueous electrolyte solutions. Although such forces control the approach and binding of particles in electrolytes and hence have large practical significance they are poorly known. In recent work I established a rigorous scheme for calculation of the electrostatic contribution to the force and proved its feasibility. In order to realise practical applications, such as in drug design, we must know the mean force between an ion and a surface or functional surface group. Here I propose to perform the required simulations and explore the analytical simplifications.Read moreRead less
Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex ....Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex intracellular signalling networks. This is an important step towards identifying new drug targets that are responsible for tumour growth. Australian science will benefit from the training of new scientists in modern, post-genome technologies where there is currently a world shortage of experienced personnel.Read moreRead less
Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that tr ....Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that translate external signals into the right cellular responses. The proposed experiments will provide a unique structural framework by which we can understand how these signals are transmitted. Such knowledge is an important foundation for advances in biomedical research and biotechnology applications.Read moreRead less
Structure and function of the protein translocation channels in the mitochondrial outer membrane. Biological membranes are the basis of life and understanding how proteins are inserted into membranes is a major goal in the Biological Sciences. The TOM complex is a molecular machine mediating protein insertion into a biological membrane. Recent successes with X-ray diffraction of protein crystals, and solution and solid-state NMR spectroscopy have heralded leaps-and-bound advances for our knowled ....Structure and function of the protein translocation channels in the mitochondrial outer membrane. Biological membranes are the basis of life and understanding how proteins are inserted into membranes is a major goal in the Biological Sciences. The TOM complex is a molecular machine mediating protein insertion into a biological membrane. Recent successes with X-ray diffraction of protein crystals, and solution and solid-state NMR spectroscopy have heralded leaps-and-bound advances for our knowledge of how membranes work at the molecular level. Using a combination of phylogenetic analysis, yeast genetics and these new techniques from structural biology, we will characterize the structure and function of the core from the TOM complex.Read moreRead less
Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcom ....Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcome the challenges of flexibility in these systems. The proteins we will study are not found in humans, and hence our research will provide important structural data on potential targets for the design of novel antibiotics to fight bacterial infection.Read moreRead less