Transcription factor – enhancer – promoter based regulatory networks. This project aims to develop new understanding on how multicellular organisms (including humans) develop, and how mutations in distant regions of the genome can affect human traits. The way the human genome is interpreted by the cellular machinery is still a mystery. We have a reference sequence and know where the majority of coding genes are, but we are far from understanding how the genome is regulated to generate the divers ....Transcription factor – enhancer – promoter based regulatory networks. This project aims to develop new understanding on how multicellular organisms (including humans) develop, and how mutations in distant regions of the genome can affect human traits. The way the human genome is interpreted by the cellular machinery is still a mystery. We have a reference sequence and know where the majority of coding genes are, but we are far from understanding how the genome is regulated to generate the diversity of cell types in our bodies. Enhancer regions interact with proximal promoters to regulate gene expression level and tissue-specificity. This project aims to develop transcriptional regulatory network models using high throughput chromatin interaction data and expression perturbation to link promoter and enhancers genome-wide.Read moreRead less
The structure in four-dimensions of a mammalian nuclear body. The project aims to develop a working model of a micron-sized molecular machine implicated in numerous aspects of gene regulation. Bodies in the mammalian cell nucleus are larger than macromolecular complexes and smaller than organelles. Recent developments in structural, molecular and cell biology are allowing us to begin to interpret their structure-function relationships. This project capitalises on a wealth of structural and funct ....The structure in four-dimensions of a mammalian nuclear body. The project aims to develop a working model of a micron-sized molecular machine implicated in numerous aspects of gene regulation. Bodies in the mammalian cell nucleus are larger than macromolecular complexes and smaller than organelles. Recent developments in structural, molecular and cell biology are allowing us to begin to interpret their structure-function relationships. This project capitalises on a wealth of structural and functional data on nuclear bodies termed paraspeckles with the aim of developing a structural model. It aims to track tens of proteins and long non-coding RNA from paraspeckles as they proceed through the cell cycle, by combining genome engineering, super-resolution microscopy, proteomics and in vitro interaction studies.Read moreRead less