Evolution, structure and function of key components in a molecular machine. The project will provide the basis for training of students and personnel in the previously recognized priority "Genomes-Phenomes", still the central theme of modern biology. In particular,
collaborations established with the Los Alamos National Laboratory in New Mexico will transfer to Australia expertise in the cutting edge discipline of small angle scattering for analysis of biologically important molecules. Such tr ....Evolution, structure and function of key components in a molecular machine. The project will provide the basis for training of students and personnel in the previously recognized priority "Genomes-Phenomes", still the central theme of modern biology. In particular,
collaborations established with the Los Alamos National Laboratory in New Mexico will transfer to Australia expertise in the cutting edge discipline of small angle scattering for analysis of biologically important molecules. Such training is essential for developing a future pool of skilled Australian scientists to staff and utilise the major national infrastructure developments represented by the Replacement Research Reactor and Australian Synchrotron, as outlined in the National Research Priority "Frontier Technologies".Read moreRead less
Investigating the subunit interactions of a molecular protein import machine. The project will provide fundamental knowledge of how sophisticated natural molecular machines interact with their substrates in plants and animals. It will also provide the basis for training of students and personnel in a range of structural biology technologies including several that are not commonly used by biologists, but make use of two major facilities that have been invested in by our government, namely the Aus ....Investigating the subunit interactions of a molecular protein import machine. The project will provide fundamental knowledge of how sophisticated natural molecular machines interact with their substrates in plants and animals. It will also provide the basis for training of students and personnel in a range of structural biology technologies including several that are not commonly used by biologists, but make use of two major facilities that have been invested in by our government, namely the Australian Synchrotron and the OPAL Research Reactor.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 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
Preparation of Photo-Affinity Molecular Probes for the Identification of Gibberellin Receptors. Bioactive gibberellins affect numerous processes during plant growth and development, including seed germination, leaf expansion, stem elongation, flowering and fruit development. However, only very limited information is available regarding their mode of action at the molecular level. The central aim of the project is to prepare a family of photo-affinity molecular probes based on the gibberellin m ....Preparation of Photo-Affinity Molecular Probes for the Identification of Gibberellin Receptors. Bioactive gibberellins affect numerous processes during plant growth and development, including seed germination, leaf expansion, stem elongation, flowering and fruit development. However, only very limited information is available regarding their mode of action at the molecular level. The central aim of the project is to prepare a family of photo-affinity molecular probes based on the gibberellin molecule that will be designed to provide critical information on the location and structure of gibberellin receptors. Screening of the probes for potential effectiveness will be determined initially by the measurement of alpha-amylase produced in a standard barley aleurone assay.Read moreRead less
O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphat ....O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphate modified proteins. For example, there may be consequences for the model of hyperphosphorylated and carbohydrate modified proteins involved in neurodegeneration. There will also be a targeted benefit. An improved understanding of the mechanism of neurotransmission will benefit in designing compounds to fight diseases of neurotransmission.Read moreRead less
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
Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated c ....Identifying mitogenic signalling proteins with phosphatidyl inositol lipids. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids attached to 'fishing lines' we can search for, identify and study the function of all the downstream signalling proteins in activated cancer cells. This will provide the basic information for drug discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less
Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can sea ....Synthesis of phosphatidylinositol and inositol polyphosphate derivatives to probe key signalling proteins associated with cell growth and cancer. Health care of an ageing population is a national priority of the community. In order to understand the factors that control cell growth and death in cancer cells signalling proteins can be identified and studied and compared with model systems from quiescent cells. Using phospholipids and inositol polyphosphates attached to 'fishing lines' we can search for, identify and study the function of many of the downstream signalling proteins in activated cancer cells. This will provide the basic information for discovery processes to target specific molecules that inhibit and control the function of the signalling proteins implicated in the growth of cancer cells.Read moreRead less
Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of ....Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of VR1 receptor activation and provide information on how the VR1 receptor is regulated. We will determine and compare neurotoxicity of these compounds to capsaicin which is known to possess neurotoxic activity. The outcome of this project may result in effective agents for better pain management.
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