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Unraveling the genetic networks of cancer development. Cancer causes nearly 30% of all deaths in Australia and the aging of our population means that its incidence will increase for the foreseeable future. The past two decades of cancer research have yielded great advances in identifying the genetic mutations that contribute to cancer, but our understanding of how these mutations cooperate to transform a healthy cell into a tumour cell remains limited. High-throughput genomic analysis of DNA fro ....Unraveling the genetic networks of cancer development. Cancer causes nearly 30% of all deaths in Australia and the aging of our population means that its incidence will increase for the foreseeable future. The past two decades of cancer research have yielded great advances in identifying the genetic mutations that contribute to cancer, but our understanding of how these mutations cooperate to transform a healthy cell into a tumour cell remains limited. High-throughput genomic analysis of DNA from large numbers of tumours is essential to identify and understand the combinations of cancer mutations that are most deadly. Such studies can form the basis for developing better diagnostics and new treatments for patients whose tumours are resistant to current therapies.Read moreRead less
Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a templ ....Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a template, it will develop powerful new methods to supply wholly new DNA interactive molecules with great potential as new drugs to treat cancer or other genetic diseases.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
Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will th ....Genetic manipulation of Clostridium sporogenes. The overall objective of this project is to develop genetic methods for the manipulation of the anaerobic bacterium Clostridium sporogenes. Specifically, the project aims to manipulate this microorganism so that genes encoding enzymes that convert prodrugs to anticancer drugs can be introduced and stably maintained on its chromosome. The significance of the project is that the resultant bacteria, and others constructed using these methods, will then be able to be tested for their ability to act as specific drug delivery systems for use in the treatment of solid tumours.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
Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular t ....Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular targets and possibly facilitate the future development of new therapeutic approaches to treating neuroblastoma. In addition, the project will develop know-how that can be utilised by both the industry partner and the broader research community and will introduce to Australian science novel techniques and skills. Read moreRead less
The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of ....The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of eEF2 in controlling protein synthesis, seek new substrates for eEF2 kinase and initiate work to elucidate the structure of this unusual enzyme. This will enhance, in a range of ways, fundamental understanding of cell physiology.Read moreRead less
Carbohydrates and Carbohydrate-Recognising Proteins as Drug Discovery Targets. The significance and roles of carbohydrates in many biological processes, in particular those processes associated with disease, is now well-recognised. These new directions have captured the attention and imagination of not only academic research groups across the world, but also pharmaceutical and biotechnology companies and has restimulated their interest in the pursuit of carbohydrate-based drugs and drugs against ....Carbohydrates and Carbohydrate-Recognising Proteins as Drug Discovery Targets. The significance and roles of carbohydrates in many biological processes, in particular those processes associated with disease, is now well-recognised. These new directions have captured the attention and imagination of not only academic research groups across the world, but also pharmaceutical and biotechnology companies and has restimulated their interest in the pursuit of carbohydrate-based drugs and drugs against carbohydrate-recognising proteins critical in disease processes. The current application seeks to use some of this information to faciliate the discovery of novel carbohydrate-based chemical entities as inhibitors of the spread of some cancers and diseases caused by pathogenic microorganisms.Read moreRead less
Novel Vitamin E Analogues with Enhanced Specificity for Malignant Cells. The aim of this project is to synthesise and characterise novel compounds based on vitamin E succinate that are capable of efficiently and selectively killing cancer cells. The new compounds will be tested for their ability to induce programmed cell death in cancer cells and the most active of them will be also tested for anti-cancer effect in a pre-clinical model. We believe that novel analogues based on vitamin E succinat ....Novel Vitamin E Analogues with Enhanced Specificity for Malignant Cells. The aim of this project is to synthesise and characterise novel compounds based on vitamin E succinate that are capable of efficiently and selectively killing cancer cells. The new compounds will be tested for their ability to induce programmed cell death in cancer cells and the most active of them will be also tested for anti-cancer effect in a pre-clinical model. We believe that novel analogues based on vitamin E succinate can lead to the discovery of very effcient and selective anti-cancer drugs with no side-effects that may be used for patient treatment in the future. This makes our project of exceptional significance.Read moreRead less