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
Membrane attack complex/perforin-like proteins in developmental and neurobiology. This project will aim to use the fruit fly as a model system to understand how members of the perforin-like superfamily, a family of proteins more usually associated with mammalian immunity, function in embryonic and neural development. These data will eventually provide central insight into human diseases such as cancer and autism spectrum disorder.
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.
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
Defining a role for non-coding RNAs in gonadal sex differentiation. This project aims to increase knowledge in the area of developmental biology, studying how gene regulation by so-called non-coding RNAs contributes to tissue patterning. The project plans to use a unique model system: gonadal development in the chicken embryo. It also plans to use novel molecular approaches that exploit the chicken model to study the role of microRNAs and a long non-coding RNA in patterning the embryonic gonad. ....Defining a role for non-coding RNAs in gonadal sex differentiation. This project aims to increase knowledge in the area of developmental biology, studying how gene regulation by so-called non-coding RNAs contributes to tissue patterning. The project plans to use a unique model system: gonadal development in the chicken embryo. It also plans to use novel molecular approaches that exploit the chicken model to study the role of microRNAs and a long non-coding RNA in patterning the embryonic gonad. The project aims to provide a deeper understanding of how genes operate to control tissue patterning and organogenesis. It may thus inform the field of sex determination specifically, and, more broadly, stem cell biology and tissue engineering.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.
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
Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic fr ....Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic framework. This should provide major benefits for understanding bacterial ecology and evolution, and for future studies seeking to optimise industrial processes or prevent disease. It will also directly contribute to building Australia’s capacity in computational biology- a key driver of biotechnology innovation.Read moreRead less
Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental gl ....Modern reptiles with ancient toxins: the molecular origin and evolution of novel bioactive proteins from squamate dental glands. Animal venoms provide a rich source of novel bioactive proteins, some of which have demonstrated therapeutically useful activities. Through this researcher's unique approach of investigating previously unmapped squamate venom systems, there is potential for the identification of divergent, bioactive proteins. Those already identified by the applicant in the dental glands of Australian monitor lizard species represent a tremendous opportunity for biodiscovery. Further knowledge in this area will increase medical understandings of bites and aid conservation measures informed by the natural history of these animals.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