Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biol ....How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biology, and will increase our understanding of diseases that arise due to aberrant tissue growth, such as cancer. Our research findings will thus be of substantial national benefit, given that cancer is now the biggest cause of death in Australia, and that more than 88,000 Australians are diagnosed with cancer each year. Read moreRead less
An RNA interference based genetic screen for novel epigenetic modifiers involved in mammalian X inactivation. All the information required to form an adult human is contained in the DNA of the fertilized egg. Development is achieved by a complex orchestration of genes being switched on and off, controlled by proteins called epigenetic modifiers. Sometimes this goes awry, leading to disease. Despite their vital role, only around ten percent of the potential epigenetic modifiers have been characte ....An RNA interference based genetic screen for novel epigenetic modifiers involved in mammalian X inactivation. All the information required to form an adult human is contained in the DNA of the fertilized egg. Development is achieved by a complex orchestration of genes being switched on and off, controlled by proteins called epigenetic modifiers. Sometimes this goes awry, leading to disease. Despite their vital role, only around ten percent of the potential epigenetic modifiers have been characterized in humans, making it impossible to interpret how they work together, or when they fail. We will develop a novel screen-based technology to find hundreds more true epigenetic modifiers. This technology will aid us and other Australian scientists to understand the role of epigenetics in normal development and disease, ultimately leading to better public health.Read moreRead less
Identification of genes regulating breast cancer progression and metastasis. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last thirty years, many women still die from relapse of the disease. Our goal is to identify genes involved in the regulation of breast cancer progression and metastasis. This may lead to the discovery of druggable molecules for better targeted therapies for patients.
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.
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
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
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