Radical change in the architecture of a nucleus: loss of typical DNA organisation systems in dinoflagellates. The genetic blueprint of all higher cells is stored in the cell nucleus, and proteins called histones provide the filing system for compactly stacking and organising the cell's DNA. One group of organisms, the dinoflagellate algae, have lost this histone system. This project will provide insight into their alternative DNA management systems.
Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant be ....Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant benefits, such as to the economy by offering a cost-effective alternative to sequencing methods currently used to map DNA and RNA modifications.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemi ....The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemical modifications impact cell specific gene nuclear positioning and how this regulates changes in gene expression associated with immune cell activation. An outcome will be identification of novel molecular mechanisms that will have broad applicability across cellular biology, and provide novel targets for drug development.Read moreRead less
The hunt for Ribonucleic Acid riboswitches and genetic sensors of metabolic flux in plants. Ribonucleic Acid (RNA) contains both structural and sequence information that coordinates feedback of metabolic processes in response to environmental change, thereby promoting cellular adaptation and survival. This project will discover ancient RNA modules and structural switches in plants that sense chemical reactions and regulate pathway flux.