Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water ....Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water and soil should lead to deeper understanding of the dynamics, variation and transfer of genetic material within these resources’ microbial communities, strategies to manage microbial diversity, and improved productivity and long-term sustainability for these resources.Read moreRead less
Diet influences the selective advantage of mitochondrial DNA mutations. This project aims to examine critical mechanisms that affect mitochondrial DNA variation within species. It aims to test the hypothesis that mitochondrial DNA haplotypes have the potential to be under nutritionally induced balancing selection as a consequence of cellular signalling and/or Adenosine triphosphate (ATP) production by mitochondria. Diet can vary both seasonally and geographically and is a key environmental param ....Diet influences the selective advantage of mitochondrial DNA mutations. This project aims to examine critical mechanisms that affect mitochondrial DNA variation within species. It aims to test the hypothesis that mitochondrial DNA haplotypes have the potential to be under nutritionally induced balancing selection as a consequence of cellular signalling and/or Adenosine triphosphate (ATP) production by mitochondria. Diet can vary both seasonally and geographically and is a key environmental parameter that influences the ability of a species to colonise new habitats. The project plans to characterise the functional links between specific mitochondrial DNA haplotypes, mitochondrial functions and organismal traits. The expected outcome is a more precise grasp of the processes influencing genetic variation within and among species, which would inform current issues in ecology and genetics.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
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
Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion poly ....Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion polymorphism from population sequence data. Finally, the project will use this map to assess the functional impact and evolutionary role of inversions, by assessing their effect on quantitative traits and assessing measures of selection and population differentiation. Read moreRead less
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
Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play ....Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play a key role. It will also support the development of billion dollar industries focused on the use of beneficial microbes in agriculture, plant, animal, and human health.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