Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itse ....Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itself. This project expects to unravel the functional contributions of DNA methylation to vertebrate embryogenesis by using latest cutting-edge genomics techniques. The project will be carried out on the highly tractable zebrafish model system which allows for easy genetic manipulation of the desired sequences. This project aims to provide a better understanding of embryonic development of vertebrates, including humans.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
Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how tem ....Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how temperature reverses chromosomal sex determination in dragon lizards. This could show how climatic extremes affect the biology of climate sensitive reptiles, and understand their vulnerability to climate change.Read moreRead less
The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which ....The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which sex genes are targets? Epigenetic enzymes are astonishingly conserved, providing exciting opportunities to draw from human systems to unravel novel signatures of temperature-induced sex switching in reptiles. This project will advance knowledge of developmental programming generally.Read moreRead less