Phun With Phages: Discovering Novel Bacteriophages in the Soil

We used three bacterial hosts: Mycobacterium smegmatis, Microbacterium foliorum, and Gordonia terrae, to isolate novel bacteriophages from soil samples. We named these phages, created high titer lysates, and purified their DNA genomes. We have archived the high titer lysates at Northwestern College and the University of Pittsburgh. The genomes of three of our phages were sequences at the University of Pittsburgh and we will be sequencing the remaining genomes this summer. Additionally, we are planning to image our phages with transmission electron microscopy at the University of Iowa or Nebraska yet this semester

Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers

Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these genes is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from the parietal cortex of AD autosomal dominant (APP and PSEN1) and risk-modifying variant (APOE, TREM2 and MS4A) carriers. Within individual cell types, we capture genes commonly dysregulated across variant groups. However, specific transcriptional states are more prevalent within variant carriers. TREM2 oligodendrocytes show a dysregulated autophagy-lysosomal pathway, MS4A microglia have dysregulated complement cascade genes, and APOEε4 inhibitory neurons display signs of ferroptosis. All cell types have enriched states in autosomal dominant carriers. We leverage differential expression and single-nucleus ATAC-seq to map GWAS signals to effector cell types including the NCK2 signal to neurons in addition to the initially proposed microglia. Overall, our results provide insights into the transcriptional diversity resulting from AD genetic architecture and cellular heterogeneity. The data can be explored on the online browser ( http://web.hararilab.org/SNARE/ )