Biology subjects

Bill, M.

Publications and source records attributed to Bill, M..

5 recordsLinked to original sources

bioRxiv2024

Coordinated organic and inorganic nitrogen transformations fuel soil microbial blooms and increase nitrogen retention during snowmelt

Snowmelt in high-elevation watersheds triggers a microbial bloom and crash that affects nitrogen (N) export. Predicting watershed N dynamics as snowpack declines is a challenge because the mechanisms that underlie this microbial bloom and crash are uncertain. Using a multi-omic approach, we show that the dynamic molecular properties of dissolved organic N, plus high gene expression for peptidases that recycle microbial biomass, suggested that microbial turnover provided N for biosynthesis during the microbial bloom. Amino acid fermentation by Bradyrhizobia produced organic acids that also fueled denitrification and dissimilatory nitrate reduction to ammonia (DNRA) during snowmelt. Nitrification in spring was driven by Spring-Adapted Nitrososphaerales, which utilized ammonium derived from osmolyte degradation by Winter-Adapted Solirubrobacteraceae. High DNRA gene expression after snowmelt suggested significant nitrate retention, increasing watershed N retention potential. However, declining snowfall may compromise microbial regulation of soil N retention, with implications for watershed N export.

microbiology↗

bioRxiv2024

CRISPR-enabled control of gene expression sets the isotopic composition of microbial methane

The stable isotopic composition of biogenic methane varies substantially in the environment and is routinely used to fingerprint its source. However, the underlying cause of this variation is debated. Here, we experimentally manipulate the growth rate of the model methanogen, Methanosarcina acetivorans, using CRISPR mutagenesis to generate a tunable version of the key and final enzyme in methanogenesis, methyl-coenzyme M reductase (MCR). We demonstrate that the carbon and hydrogen isotopic composition of methane change as a function of MCR expression and growth rate. Using an isotope enabled metabolic model we show that these changes stem from a substrate-independent increase in reversibility of methanogenic enzymes. Overall, these data provide a novel framework for calibrating growth coupled changes in the isotopic composition of biogenic methane.

microbiology↗

bioRxiv2023

The histone modifier KAT2A presents a selective target in a subset of well-differentiated microsatellite-stable colorectal cancers

BackgroundLysine acetyltransferase 2A (KAT2A) plays a pivotal role in epigenetic gene regulation across various types of cancer. In colorectal cancer (CRC), upregulation of KAT2A is associated with a more aggressive phenotype. Our study aims to elucidate the molecular underpinnings of KAT2A dependency in CRC and assess the consequences of KAT2A depletion. MethodsWe conducted a comprehensive analysis by integrating CRISPR-Cas9 screening data with genomics, transcriptomics, and global acetylation patterns in CRC cell lines to pinpoint molecular markers indicative of KAT2A dependency. Additionally, we characterized the phenotypic effect of a CRISPR-Cas9-mediated KAT2A knockout and chemical inhibition of KAT2A in CRC cell lines and patient- derived 3D spheroid cultures. ResultsOur findings reveal that KAT2A dependency is closely associated with a lower mutational burden and increased differentiation grade in CRC cell lines, independent of the KAT2A expression levels. KAT2A dependent CRC cell lines display enriched H3K27ac marks at gene loci linked to enterocytic differentiation. Loss of KAT2A leads to decreased cell growth and viability, downregulation of proliferation- and stem cell-associated genes, and induction of differentiation markers. ConclusionA specific subset of CRCs with a more differentiated phenotype relies on KAT2A. For these CRC cases, KAT2A might represent a promising novel therapeutic target.

cancer biology↗

bioRxiv2020

The snowmelt niche differentiates three microbial life strategies that influence soil nitrogen availability during and after winter

Soil microbial biomass can reach its annual maximum pool size beneath the winter snowpack and is known to decline abruptly following snowmelt in seasonally snow-covered ecosystems. Observed differences in winter versus summer microbial taxonomic composition also suggests that phylogenetically conserved traits may permit winter-versus summer-adapted microorganisms to occupy distinct niches. In this study, we sought to identify archaea, bacteria, and fungi that are associated with the soil microbial bloom overwinter and the subsequent biomass collapse following snowmelt at a high-altitude watershed in central Colorado, USA. Archaea, bacteria, and fungi were categorized into three life strategies (Winter-Adapted, Snowmelt-Specialist, Spring-Adapted) based on changes in abundance during winter, the snowmelt period, and after snowmelt in spring. We calculated indices of phylogenetic relatedness (archaea and bacteria) or assigned functional attributes (fungi) to organisms within life strategies to infer whether phylogenetically conserved traits differentiate Winter-Adapted, Snowmelt-Specialist, and Spring-Adapted groups. We observed that the soil microbial bloom was correlated in time with a pulse of snowmelt infiltration, which commenced 65 days prior to soils becoming snow-free. A pulse of nitrogen (N, as nitrate) occurred after snowmelt, along with a collapse in the microbial biomass pool size, and an increased abundance of nitrifying archaea and bacteria (e.g., Thaumarchaeota, Nitrospirae). Winter- and Spring-Adapted archaea and bacteria were phylogenetically clustered, suggesting that phylogenetically conserved traits allow Winter- and Spring-Adapted archaea and bacteria to occupy distinct niches. In contrast, Snowmelt-Specialist archaea and bacteria were phylogenetically overdispersed, suggesting that the key mechanism(s) of the microbial biomass crash are likely to be density-dependent (e.g., trophic interactions, competitive exclusion) and affect organisms across a broad phylogenetic spectrum. Saprotrophic fungi were the dominant functional group across fungal life strategies, however, ectomycorrhizal fungi experienced a large increase in abundance in spring. If well-coupled plant-mycorrhizal phenology currently buffers ecosystem N losses in spring, then changes in snowmelt timing may alter ecosystem N retention potential. Overall, we observed that the snowmelt separates three distinct soil niches that are occupied by ecologically distinct groups of microorganisms. This ecological differentiation is of biogeochemical importance, particularly with respect to the mobilization of nitrogen during winter, before and after snowmelt.

microbiology↗

bioRxiv2019

Taxonomically and metabolically distinct microbial communities with depth and across a hillslope to riparian zone transect

Watersheds are important for supplying fresh water, the quality of which depends on complex interplay involving physical, chemical and biological processes. As water percolates through the soil and underlying weathering rock en route to the river corridor, microorganisms mediate key geochemical transformations, yet the distribution and functional capacities of subsurface microbial communities remain little understood. We have studied metabolic capacities of microbial communities along a meadow to floodplain hillslope transect within the East-River watershed, Colorado, using genome resolved metagenomics and carbon and hydrogen stable isotopes. Very limited strain/species overlap was found at different depths below the ground surface and at different distances along the hillslope, possibly due to restricted hydraulic connectivity after early stages of snowmelt. Functions such as carbon fixation and selenate reduction were prevalent at multiple sites, although the lineages of organisms responsible tend to be location-specific. Based on its abundance, sulfur is significantly more important for microbial metabolism at the floodplain compared to on the hillslope. Nitrification and methylamine oxidation are likely only occurring within the floodplain, with nitrification capacity in shallow soil, and methylamine oxidation in deeper unsaturated sediment. Biogenic methane was detected in deep surface samples, but methanogenic organisms were not identified. Originality-Significance StatementIn a previous study within a hillslope to riparian zone transect of a sub-alpine watershed, the community structure was explored using ribosomal protein S3 genes, and the metabolic potential was hypothesized based on the presence of metabolism related genes. However, tying specific strains and species to metabolic functioning was not discussed as resolved genomes were not available. In the current study, we use genome-resolved metagenomics along with carbon and hydrogen stable isotopes to explore the spatial distribution of biogeochemical processes. By linking taxonomy and function, using multiple functional genes indicative of full metabolic pathways, we detect heterogeneity in the distribution of metabolic potential and the organisms involved with depth and landscape position. Thus, we infer how microbiome genomic variation impacts biogeochemical cycling across the watershed. We found very limited strain/species overlap at different depths below the surface and along the hillslope, possibly due to the restricted site to site hydraulic connectivity, and show that communities are largely distinct in their metabolic capacities. Both proximity to the river and the underlying Mancos shale apparently control species distribution and metabolic potential. Functions such as carbon fixation and selenate reduction were prevalent at multiple sites, although the lineages of organisms responsible tend to be location-specific. Arsenate detoxification was found to be prevalent in the riparian zone whereas selenate reduction was detected within weathered Mancos shale. We conclude that important ecosystem functions are strongly associated with the riparian zone, some of which may have crucial implications as to water quality and human health.

bioinformatics↗