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
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
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
How do transcription factors control cell fate transitions? The aim of this project is to determine how transcription factors control cellular identity, which is relevant to many biological processes including embryogenesis, cellular reprogramming and differentiation. Innovative genomic tools will be combined with various in vitro cellular conversion systems to generate fundamental mechanistic insight into how transcription factors mediate these identity changes. The knowledge gained from this w ....How do transcription factors control cell fate transitions? The aim of this project is to determine how transcription factors control cellular identity, which is relevant to many biological processes including embryogenesis, cellular reprogramming and differentiation. Innovative genomic tools will be combined with various in vitro cellular conversion systems to generate fundamental mechanistic insight into how transcription factors mediate these identity changes. The knowledge gained from this work will allow us to answer standing fundamental questions in regards to cell fate control and the biochemistry of transcription factors, which in turn will aid in the development of novel gene regulation technologies applicable to a myriad of fields and industries.Read moreRead less
Unveiling the epigenome dynamics through the pluripotency continuum. This project aims to utilise stem cells and genomics based technologies, in combination with new computational algorithms to dissect the fundamental molecular events that drive the first steps during development. The project is expected to unveil the basic mechanisms underpinning how genes driving the developmental master plan are controlled in cells that have the capacity to give rise to the whole organism and placenta. The kn ....Unveiling the epigenome dynamics through the pluripotency continuum. This project aims to utilise stem cells and genomics based technologies, in combination with new computational algorithms to dissect the fundamental molecular events that drive the first steps during development. The project is expected to unveil the basic mechanisms underpinning how genes driving the developmental master plan are controlled in cells that have the capacity to give rise to the whole organism and placenta. The knowledge gained from this work will inform and guide future novel approaches, such as in assisted reproductive technologies or regenerative medicine.Read moreRead less
Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, ....Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, and timed cultures. The assays will involve maintenance of reprogramming ability and erasure of somatic gene transcription. By subtractive elimination the function of isolated proteins which are involved in reprogramming will be identified for potential recombinant production.Read moreRead less
Controlling cell polarity and asymmetric cell division in space and time. This project seeks to increase our understanding of how cells divide. Asymmetric cell division is a specialised form of cell division essential for the development of all organisms. The two meiotic divisions of the oocyte are extreme examples of asymmetric cell division that allow a reduction in chromosome content while retaining cytoplasmic vestments necessary for development. Successful asymmetric cell division requires ....Controlling cell polarity and asymmetric cell division in space and time. This project seeks to increase our understanding of how cells divide. Asymmetric cell division is a specialised form of cell division essential for the development of all organisms. The two meiotic divisions of the oocyte are extreme examples of asymmetric cell division that allow a reduction in chromosome content while retaining cytoplasmic vestments necessary for development. Successful asymmetric cell division requires the integration of cell cycle events with cell polarity. Understanding how this is achieved would improve our understanding of how to generate a healthy embryo in women, endangered species and in animals of commercial importance.Read moreRead less
Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cel ....Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cell movement in mammalian organ formation and develop advanced cell segmentation and tracking methods for use in the scientific community. We anticipate this project will generate fundamental insights into how cells interact to build complex organs.Read moreRead less