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
Cellular genomic approach to the pathogenesis of multiple sclerosis. This project compares the levels of gene usage in two important immune cell types between patients with multiple sclerosis and people who do not have the disease. It aims to identify the molecular basis for the disease, in order to identify new diagnostic, preventative and treatment options.
The genetic regulation of organogenesis: endoderm development in the Drosophila embryo. Embryonic development is an important research field in biology, not only for its extraordinary complexity but also because of the insights it provides into molecular processes that underpin a variety of diseases. This project aims to discover genes and molecules that regulate the normal development of one of the most important organs, the gut.
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less
Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less
Development of the PD GeneChip: a research and diagnostic tool for Parkinson's disease. The PD GeneChip will provide both social and economic benefits to Australia. It will be a key research platform for Australian scientists, and will facilitate collaboration both within Australia and overseas. It will assist with health care management of PD (Parkinson's disease) patients by providing a cost-effective diagnostic tool and the possibility of predicting the clinical course of disease. This inform ....Development of the PD GeneChip: a research and diagnostic tool for Parkinson's disease. The PD GeneChip will provide both social and economic benefits to Australia. It will be a key research platform for Australian scientists, and will facilitate collaboration both within Australia and overseas. It will assist with health care management of PD (Parkinson's disease) patients by providing a cost-effective diagnostic tool and the possibility of predicting the clinical course of disease. This information will provide the basis for tailoring treatment to a patients needs. It is anticipated that marketing of the PD GeneChip within Australia and overseas may produce revenue of at least $40 million annually.Read moreRead less
Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood for ....Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood formation will be studied. We will establish techniques for several steps that will be useful for all zebrafish mapping projects. We expect the genetic characterization of these mutants to provide new insights into nerve cell survival, gut development, and blood formation.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the ....Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the most fundamental questions in the whole of biology: what is the basis for the primal distinction between sex and soma?Read moreRead less
How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. ....How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. This research will continue Australia's high profile in reproductive biology using one of our iconic native mammals. A greater understanding of marsupial reproduction will also contribute to management of our threatened marsupial populations.Read moreRead less