Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell sign ....Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell signal transduction that drive cell division, differentiation and transformation and may enable the design of new anticancer therapies. Importantly, the modelling and simulation methods developed in the project will have a general applicability to other complex systems such as sustainable ecological systems.Read moreRead less
Examining the relationship between error processing, cognitive control and emotion: a cognitive neuroscience approach. The proposed research aims to contribute to current scientific thinking on how the processing of errors influences self-monitoring and cognitive performance. The ability to monitor one's cognitive performance deteriorates with normal ageing, and is particularly affected in a range of clinical conditions, where it is a reliable predictor of a poor prognostic outcome. This project ....Examining the relationship between error processing, cognitive control and emotion: a cognitive neuroscience approach. The proposed research aims to contribute to current scientific thinking on how the processing of errors influences self-monitoring and cognitive performance. The ability to monitor one's cognitive performance deteriorates with normal ageing, and is particularly affected in a range of clinical conditions, where it is a reliable predictor of a poor prognostic outcome. This project aims to clarify understanding of the cognitive and neural processes underlying self-monitoring, as an important first step to improving rehabilitation and management methods for age-related impairments such as Alzheimer's disease, and prominent mental health conditions such as schizophrenia.Read moreRead less
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. T ....Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. This project will provide new compounds of potential clinical use in the treatment of cancer, thereby aiding the large population of Australians who will be affected by this disease. Furthermore, the new advanced materials produced by this project will aid in the study of biochemical processes involved in cancer.Read moreRead less
Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting ....Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting of tumours while protecting healthy tissue from damage. Post-treatment skin photosensitivity will be minimised by antioxidant features integrated into the photosensitisers. The development of improved photosensitisers during this project will ultimately lead to improved treatment and new alternatives for Australian cancer sufferers.Read moreRead less
Anticancer Agents from Australian Marine Biodiversity. This project aims to initiate a proof of concept research collaboration in order to detect, isolate, characterise, identify and evaluate new marine anticancer drugs. This will be achieved through screening Australian marine biodiversity for the ability to inhibit key processes in tumor cell physiology. Significant outcomes from the project will not only be targets that yield new anticancer agents, but also the participation of Australian r ....Anticancer Agents from Australian Marine Biodiversity. This project aims to initiate a proof of concept research collaboration in order to detect, isolate, characterise, identify and evaluate new marine anticancer drugs. This will be achieved through screening Australian marine biodiversity for the ability to inhibit key processes in tumor cell physiology. Significant outcomes from the project will not only be targets that yield new anticancer agents, but also the participation of Australian researchers in the environmentally sustainable exploration, discovery and development of next generation anticancer drugs from Australia's unique marine biodiversity. Read moreRead less
Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry ....Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry for targeted drug design, which could realise benefits in the form of novel medical treatments and reduced side effects. The monolayer template technology will also extend the capabilities of the National Cryo-EM facility, the infrastructure of which, is open for all Australian researchers. Read moreRead less
The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this a ....The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this assay could provide a useful diagnostic tool in a clinical environment that would allow for the rapid assessment of these diseases, their progression and indeed response to therapy.Read moreRead less
Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million ....Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million years ago. A major outcome of this reconstruction will be a fundamental understanding of how cells communicate with each other during the process of development to give rise to the diversity of cell types within multicellular animals. This study will also shed light on what happens when cell communication goes astray, as observed in a range of human malignancies, including cancer. Read moreRead less
Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis ....Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis here will be in the relationship between the two proteins in co-ordinating the repair of breaks in DNA. This information will be important in understanding mechanisms for maintaining the integrity of the genome.Read moreRead less