Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.Read moreRead less
The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be importan ....The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be important for developing new control strategies for diseases of global significance such as malaria or toxoplasmosis, as well as those of national importance to the food industry of Australia, including diseases like babesiosis and coccidiosis that cause significant economic loss to the livestock and poultry industries each year.Read moreRead less
Structure and function of a new class of multi-zinc finger (MZF) transcriptional regulators. An understanding of how genes are switched on and off during the development and lifetime of an organism is central to developing the ability to fight many diseases in a rational way. This project will advance our knowledge in this area at a fundamental molecular level by examining the mechanisms through which a specific set of proteins controls gene expression.
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.
Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge ma ....Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge may also shed light on the basis of congenital abnormalities and other pathological processes and possibly help us to understand how to prevent or treat these conditions.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
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
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
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.