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
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.
Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for ....Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for important agronomic traits including disease resistance, flowering time and legume nitrogen fixation which will enable plant breeders to identify and apply novel genes and allelic variants for use in breeding programmes, accelerating the production of improved crop varieties.Read moreRead less
Variation in the arginine vasopressin 1a receptor (AVPR1a) gene, the social environment, general health and wellbeing. The project aims to investigate how the arginine vasopressin 1a gene affects gene expression and influences social behaviour and ultimately health and wellbeing. This research will contribute to understanding the importance of individual differences in social policy and interventions aimed at improving health and wellbeing.
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
Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the pr ....Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the proposed project is to elucidate these important aspects of circRNA biogenesis. Specifically, the project aims to (a) discover proteins that regulate circRNA expression, (b) elucidate how circRNA expression interacts with alternative splicing, and (c) identify circular RNAs that play regulatory roles in gene expression. Read moreRead less
The Stemformatics gene expression compendium: development of multivariate statistical approaches for cross platform analyses. Scientific data is gathered in many different forms, but there are significant gaps in our ability to analyse multiple datasets when generated on different pieces of equipment. This project will study three typical research questions in stem cell biology to develop new analytical approaches to help solve this major data gap.
Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will gene ....Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will generate basic scientific knowledge and new intellectual property that will afford new opportunities for research and development. The outcomes of this project will help to devise strategies to treat diseases such as autoimmunity, cancer and metabolic syndrome, and will thus benefit veterinary and human health.Read moreRead less
RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with ....RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with mechanism and function determined by novel CRISPR editing of a transgenic mouse model. The significant benefit will be a more complete understanding of RNA mechanisms of immune response, which will be critical in informing future advances in the rapidly developing areas of RNA-based biotechnologies and synthetic immunology.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