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
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
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