Project description:The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.
Project description:Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to phenotypic diversity, its interaction with genetic variation requires further investigation. MethylC-seq from naturally-occurring Arabidopsis accessions
Project description:We investigated natural inter-individual variation of the epigenome in a quantitative manner. To probe the degree of natural epigenomic diversity in S. cerevisiae, we compared three unrelated wild strains using replicated Mnase-seq and ChIP-seq profiling at mononucleosomal resolution for five histone marks (H3K4me3, H3K9ac, H3K14ac and H4K12ac and H3K4me1).
Project description:Freshwater environments such as rivers receive effluent discharges from wastewater treatment plants, representing a potential hotspot for antibiotic resistance genes (ARGs). These effluents also contain low levels of different antimicrobials including biocides and antibiotics such as sulfonamides that can be frequently detected in rivers. The impact of such exposure on ARG prevalence and microbial diversity of riverine environment is unknown, so the aim of this study was to investigate the release of a sub-lethal concentration (<4 g L-1) of the sulfonamide compound sulfamethoxazole (SMX) on the river bacterial microbiome using a microflume system. This system was a semi-natural in-vitro microflume using river water (30 L) and sediment, with circulation to mimic river flow. A combination of ‘omics’ approaches were conducted to study the impact of SMX exposure on the microbiomes within the microflumes. Metaproteomics did not show differences in ARGs expression with SMX exposure in water.
Project description:The Global Diversity lines are a resource collection of 87 strains of Drosophila melanogaster (Grenier JK et al 2015. PMID 25673134). In this experiment, whole adult flies from the Global Diversity Lines (87 inbred lines derived from natural populations) were profiled using a spotted-oligo microarray to determine natural variation in gene expression patterns.
Project description:Time series metasecretomes (weeks 1, 3, 5 and ten) of lignocellulose responsive microbiomes enriching on Spartina anglica biomass for 16 weeks in a natural UK salt marsh (Welwick, Humber estuary).
Project description:Exceptional preservation of endogenous organics such as collagens and osteocytes has been frequently reported in Mesozoic dinosaur fossils. The persistence of soft tissue in Mesozoic fossil bones has been challenged because of the susceptibility of proteins to degradation and because bone porosity allows microorganisms to colonize the inner microenvironments through geological time. Although protein lability has been studied extensively, the genomic diversity of microbiomes in dinosaur fossil bones and their potential roles in bone diagenesis remain underexplored. Genome-resolved metagenomics and metaproteomics were performed, therefore, on the microbiomes recovered from a Late Cretaceous Centrosaurus bone and its encompassing mudstone that were aseptically excavated in Dinosaur Provincial Park, Alberta, Canada, in order to provide insight into the genomic potential for bone alteration.
Project description:Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to phenotypic diversity, its interaction with genetic variation requires further investigation.