Discovery of novel microRNA biogenesis and functional components. Discovery of novel microRNA components will provide new strategies for confronting a diverse array of challenges Australia faces, such as the increasing rates of certain cancers in our population, to stresses on our crop plants faced with environmental changes. The biological mechanisms underlying these disparate problems are unified by microRNA involvement in many instances. By finding microRNA controlling factors common to all h ....Discovery of novel microRNA biogenesis and functional components. Discovery of novel microRNA components will provide new strategies for confronting a diverse array of challenges Australia faces, such as the increasing rates of certain cancers in our population, to stresses on our crop plants faced with environmental changes. The biological mechanisms underlying these disparate problems are unified by microRNA involvement in many instances. By finding microRNA controlling factors common to all higher organisms, we expect our community will benefit from the increased knowledge base that will help our researchers adopt new strategies in fighting diseases and improving our agricultural industry.Read moreRead less
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding ....Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding protein domains with the goal of selectively blocking these inappropriate interactions. Additionally, these engineered proteins have potential uses as biochemical tools such as to help delineate the functions of natural proteins with no known functions.Read moreRead less
Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.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
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
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less
Synthetic Endonucleases: Novel DNA Cleaving Agents for Cancer Chemotherapy. Cancer is a common disease in our society, with more than 1 in 4 of us dieing from it. The current survival rate is 50%, and has been so for the past 5 decades. Thus, there is clearly an urgent need for better forms of therapy. Chemotherapy is the mainstay of treatment once the disease has spread from its original site. The National Benefits from the development of a new class of effective cancer drug are two-fold. Firs ....Synthetic Endonucleases: Novel DNA Cleaving Agents for Cancer Chemotherapy. Cancer is a common disease in our society, with more than 1 in 4 of us dieing from it. The current survival rate is 50%, and has been so for the past 5 decades. Thus, there is clearly an urgent need for better forms of therapy. Chemotherapy is the mainstay of treatment once the disease has spread from its original site. The National Benefits from the development of a new class of effective cancer drug are two-fold. Firstly, much relief will come to people suffering from cancer, as some will live longer, and some will be cured. Secondly, the economic benefits are extensive, since the world market in cancer drugs is measured in billions $US, and significant monies will flow to those who hold the intellectual property rights. Read moreRead less
Near Unsupervised Learning for Early Discovery of Novel Patterns: Methods, Scalability and Label Dependability. This project aims to predict the unknown class labels using the existing small number of class labels. The outcomes of the project have direct relevance to the economy, environment, energy and health sectors due to the abundance of data coming out of these areas. For example, if an oncogene, a gene that can cause cancer when mutated can be found using data with only few labels and a la ....Near Unsupervised Learning for Early Discovery of Novel Patterns: Methods, Scalability and Label Dependability. This project aims to predict the unknown class labels using the existing small number of class labels. The outcomes of the project have direct relevance to the economy, environment, energy and health sectors due to the abundance of data coming out of these areas. For example, if an oncogene, a gene that can cause cancer when mutated can be found using data with only few labels and a large amount of unlabelled data, the costs and time needed for lab experimentation can be greatly reduced enabling pharmaceutical companies to develop corresponding medicines quicker. It will not only save more lives but also generates millions of dollars of income.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less