Project description:Comparative genomic hybridization between Escherichia coli strains to determine core and pan genome content of clinical and environmental isolates
Project description:The selection of bioengineering platform strains and engineering strategies to improve the stress resistance of Saccharomyces cerevisiae remains a pressing need in bio-based chemical production. Thus, a systematic effort to exploit the genotypic and phenotypic diversity to boost yeast’s industrial value is still urgently needed. Here, we analyzed 5400 growth curves obtained from 36 S. cerevisiae strains and comprehensively profiled their resistances against 13 industrially relevant stresses. We observed that bioethanol and brewing strains exhibit higher resistance against acidic conditions, however, plant isolates tend to have wider range of resistance, which may be associated with their metabolome and fluxome signatures in TCA cycle and fatty acid metabolism. By deep genomic sequencing we found that industrial strains have more genomic duplications especially affecting transcription factors, presenting disparate evolutionary paths in comparison to the environmental strains which have more InDels, gene deletions and strain-specific genes. Genome-wide association studies coupled with protein-protein interaction networks uncovered novel genetic determinants of stress resistances. These resistance-related engineering targets and strain rankings provide a valuable source for engineering significantly improved industrial platform strains.</br></br> This metabolomic study of 36 yeast strains measured intra- and extracellular metabolome under standard glucose medium, profiled by GS-MS. This is part of a multi-omic study on yeast strain collection.
Project description:Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan. Phylogenetic analyses pointed to genes and environmental factors that strongly interact to modulate the observed aging patterns. We then identified genetic networks causally associated with natural variation in replicative lifespan across wild yeast isolates, as well as genes, metabolites and pathways, many of which have never been associated with yeast lifespan in laboratory settings. In addition, a combined analysis of lifespan-associated metabolic and transcriptomic changes revealed unique adaptations to interconnected amino acid biosynthesis, glutamate metabolism and mitochondrial function in long-lived strains. Overall, our multi-omic and lifespan analyses across diverse isolates of the same species shows how gene-environment interactions shape cellular processes involved in phenotypic variation such as lifespan.
Project description:Whole-genome sequencing on PacBio of laboratory mouse strains. See http://www.sanger.ac.uk/resources/mouse/genomes/ for more details. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:We investigated how yeast cells deficient in performing homologous recombination-mediated DNA repair due to a deletion of the critical RAD52 gene respond to irreparable DNA damage inflicted by genotoxic treatment commonly applied in cancer therapy (camptothecin and irradiation). We found that upon persistence of irreparable DNA damage, yeast rad52 mutants readily undergo checkpoint adaptation accompanied by the acquisition of resistance to further genotoxic insults as well as the development of aneuploidy. Together, our findings can be used to elucidate how repair-defective cancer cells can become treatment-resistant thereby providing a way to target these resistant cell clones by tackling their aneuploidy-associated phenotypes. To investigate these characteristics commonly present in aneuploid cells in our experimental set-up, we treated yeast cells with genotoxic agents and performed whole genome sequencing. We could identify frequent whole chromosome loss events manifesting in a sensitivity of cells to aneuploidy-targeting agents.
Project description:Low coverage whole-genome sequencing have been performed on uterine leiomyosarcoma to uncovered novel potential driver genes and recurrently affected pathways.