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.
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
Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity ....Studies on the regulation of the pro-apoptotic protein Bim in mammalian development and cancer. This project is aimed at understanding the regulation of a gene, which is a tumour suppressor and is often mutated or down regulated in many different forms of cancers. A better understanding of how this gene works may eventually lead to better therapeutics to treat these cancers. This is relevant in the Australian context given that our aging population and obesity epidemics (the link between obesity, insulin resistance and various forms of cancers is well established) are leading to a rapid increase in new cancer cases, thus driving a rapid increase in demand for better treatments. This is particularly relevant in Indigenous health where obesity is on the rise following the transition from a traditional to an urban lifestyle.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
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
Elucidation of the hierarchy of stem, progenitor and mature cells in the mouse mammary gland. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last 30 years, many women still die from the disease. It is therefore important to identify new targets for breast cancer treatment. There is growing interest in the concept that a cancer-initiating cell may arise from a stem cell or progenitor cell in the mammary gland. O ....Elucidation of the hierarchy of stem, progenitor and mature cells in the mouse mammary gland. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last 30 years, many women still die from the disease. It is therefore important to identify new targets for breast cancer treatment. There is growing interest in the concept that a cancer-initiating cell may arise from a stem cell or progenitor cell in the mammary gland. Our goal is to identify those cells and to determine which genes are involved in transforming a normal cell to a cancerous cell.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
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
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.
Control of cell survival by the Bcl-2 protein family. The control of apoptosis is essential for homeostasis. It is now realized that deregulation of apoptosis is a hallmark of many cancers. In apoptosis, the Bcl-2 protein family plays a central role in determining if a cell lives or dies. My proposal aim is to provide a deeper understanding of how cell death and survival is controlled by the Bcl-2 family. These studies have notable implications for understanding normal cell death control as well ....Control of cell survival by the Bcl-2 protein family. The control of apoptosis is essential for homeostasis. It is now realized that deregulation of apoptosis is a hallmark of many cancers. In apoptosis, the Bcl-2 protein family plays a central role in determining if a cell lives or dies. My proposal aim is to provide a deeper understanding of how cell death and survival is controlled by the Bcl-2 family. These studies have notable implications for understanding normal cell death control as well as aid in the development of therapeutic agents such as ones to overcome the resistance to apoptosis, found in many types of cancer.Read moreRead less