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David Chandler

Publications and source records attributed to David Chandler.

2 recordsLinked to original sources

Comparative genomics and phenotypic divergence of ERIC I and ERIC II genotypes of Paenibacillus larvae, the causative agent of American Foulbrood disease.

Honeybees of the species Apis mellifera are important pollinators of crops and wild plants. Paenibacillus larvae, a spore-forming bacterium, is a problematic pathogen that causes American foulbrood (AFB) in honeybee larvae worldwide. In many countries, AFB is a notifiable disease, requiring the destruction of diseased colonies, resulting in economic loss that impacts beekeeping and agriculture. Disease onset starts with larval ingestion of P. larvae spores, which germinate into growing cells that proliferate in the larval gut, leading to larval death and eventually bee colony collapse. As infection progresses, P. larvae produce spores, reinitiating the disease cycle. Thus, growth, sporulation and germination underlie AFB. In this study, using various microbiological assays, quantitative cell biology methods, transmission electron microscopy and genomics, we sought to identify genetic and phenotypic characteristics associated with the predominant ERIC I and ERIC II genotypes of P. larvae during growth, sporulation and germination. Extending previous findings, our data identify genetic differences between ERIC I and ERIC II strains and some genetic variation between strains of the same ERIC type. Furthermore, we describe significant differences in cellular morphology during growth, differences in spore envelope structure and differences in germination efficiency between ERIC I and ERIC II genotypes. Collectively, our findings improve understanding of P. larvae biology and provide a foundation for developing genotype-specific disease management strategies for AFB.

Animals

Genome topology analysis and transcriptomics of human osteoclasts reveals enhancer-promoter interactions at loci for bone traits and diseases.

Genome-wide association studies (GWAS) relevant to osteoporosis have identified hundreds of loci; however, understanding how these variants influence the phenotype is complicated because most reside in non-coding DNA sequence that serves as transcriptional enhancers and repressors. To advance knowledge on these regulatory elements in osteoclasts (OCs), we performed Micro-C analysis, which informs on the genome topology of these cells and integrated the results with transcriptome and GWAS data to further define loci linked to BMD. Using blood cells isolated from 4 healthy participants aged 31-61 yr, we cultured OC in vitro and generated a Micro-C chromatin conformation capture dataset. We characterized chromatin loops (CLs) in OC from among more than 69 million chromatin interactions identified in the genome. Of the CL identified in OC, >16 000 were unique compared to precursor cells. When sentinel single nucleotide polymorphisms from osteoporosis and bone-related GWAS and those in linkage disequilibrium at r 2 > 0.6 were mapped to CL for OC, 12 588 of these variants were observed within chromatin contact regions. Notable in differential gene ontology enrichment analyses of the topology data for OC and precursors were pathways regulating pluripotency of stem cells, Wnt signaling, nucleotide-binding oligomerization domain (NOD)-like receptor signaling and chemokine signaling. These data, in combination with other 3D genome architecture and epigenetic data (eg, histone modifications and chromatin accessibility), will be useful in modeling to predict genome-wide, which enhancers regulate which genes in OC. This data will therefore also be informative for resolving GWAS hits. In conclusion, we have generated a high-resolution genome topology dataset for human OC and have used this to identify CLs relevant to studies of the genetics of osteoporosis. This data will serve as a powerful resource to inform future functional studies of OC biology.

BMD