Information theoretic approaches to optimise genome wide association studies with application to continuous and discrete traits. This project aims to develop new mathematical methods to find genetic associations from new genome-wide studies of colorectal cancer and breast cancer risk factors. If successful, this will result in improved use of expensive genetic data to better predict and understand diseases, conditions and other characteristics for humans, animals and plants.
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
The molecular control of lymphatic vascular differentiation. This project aims to improve our understanding of how a new vascular system forms and the molecules that control this process. Lymphatic vasculature plays roles in fluid drainage, inflammation, obesity, metastasis and tissue repair, yet we cannot readily promote or inhibit lymphatic vessel formation. This project aims to build new knowledge that is expected to improve our ability to generate lymphatic vessels for stem cell application ....The molecular control of lymphatic vascular differentiation. This project aims to improve our understanding of how a new vascular system forms and the molecules that control this process. Lymphatic vasculature plays roles in fluid drainage, inflammation, obesity, metastasis and tissue repair, yet we cannot readily promote or inhibit lymphatic vessel formation. This project aims to build new knowledge that is expected to improve our ability to generate lymphatic vessels for stem cell applications, tissue engineering, tissue repair and regeneration. This project will use zebrafish embryos, new genomic datasets and novel tools to uncover the genetic control of this process, and should have implications in stem cell biology, tissue engineering, repair and regeneration.Read moreRead less
Understanding how cells compact and segregate DNA in vertebrates. How a cell compacts and divides its DNA is still a major unanswered question in biology. This project will determine the way in which a cell compacts its DNA nearly ten thousand fold to allow the faithful and accurate segregation to daughter nuclei.
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.
Skeletome - A Curated Online Knowledge Base Integrating Clinical and Biological Information on Skeletal Dysplasias and Related Conditions. The skeletal dysplasia knowledge base will:
* establish Australia as a world-leader in skeletal dysplasia research;
* provide researchers with an extensible and comprehensive online knowledge-base related to skeletal dysplasias;
* enhance clinicians' understanding of the diagnosis, treatment and management of skeletal dysplasias;
* facilitate collaborativ ....Skeletome - A Curated Online Knowledge Base Integrating Clinical and Biological Information on Skeletal Dysplasias and Related Conditions. The skeletal dysplasia knowledge base will:
* establish Australia as a world-leader in skeletal dysplasia research;
* provide researchers with an extensible and comprehensive online knowledge-base related to skeletal dysplasias;
* enhance clinicians' understanding of the diagnosis, treatment and management of skeletal dysplasias;
* facilitate collaborative discussions by patients, clinicians and researchers around specific cases to improve training, management and diagnosis; and
* enhance Australia's research expertise in Semantic Web and social networking technologies.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
Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaborati ....Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaboration between a leading UK and two Australian research groups. In doing so we will provide an explanation at the molecular level for one of the great unresolved phenomena in biology: why do cold-blooded animals get bigger in the cold? The research also leads to the potential to manipulate body size in animals.Read moreRead less
Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importan ....Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importance on the regulatory function of miRNAs. Such information is critical in the future development of targeted therapeutics.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