Calder, R. | Search bioRxiv

bioRxiv2025

Viral community diversity in the rhizosphere of the foundation salt marsh plant Spartina alterniflora

Viruses of microorganisms impact microbial population dynamics, community structure, nutrient cycling, gene transfer, and genomic innovation. In wetlands, root-associated microbial communities mediate key biogeochemical processes important for plants involved in ecosystem maintenance. Nonetheless, the presence and role of microbial viruses in salt marshes remains poorly understood. In this study, we analyzed 24 metagenomes retrieved from the root zone of Spartina alterniflora, a foundation plant in salt marshes of the eastern and Gulf coasts of the U.S. The samples span three plant compartments--bulk sediment, rhizosphere, and root--and two cordgrass plant phenotypes: short and tall. We observed differentiation between phenotypes and increased similarity in viral communities between the root and rhizosphere, indicating that plant compartment and phenotype shape viral community composition. The majority of viral populations characterized are novel at the genus level, with a subset predicted to target microorganisms known to carry out key biogeochemical functions. The findings provide a holistic assessment of plant-associated viral diversity and community composition as well as identifying potential targets for exploring viral modulation of microbially-mediated ecosystem functioning in intertidal wetlands. ImportanceSalt marshes are vital coastal ecosystems. Microbes in these environments drive nutrient cycling and support plant health, with Spartina alterniflora serving as a foundation species. This study explores viral communities associated with S. alterniflora, revealing how plant compartment and phenotype shape viral composition. The discovery of numerous novel viruses, some potentially influencing microbes involved in key biogeochemical processes, highlights their ecological significance. Given the increasing pressures on coastal ecosystems, understanding virus-microbe-plant interactions is essential for predicting and managing ecosystem responses to environmental change.

genomics↗

bioRxiv2024

Gene Regulatory Network topology governs resistance and treatment escape in glioma stem-like cells

Poor prognosis and drug resistance in glioblastoma (GBM) manifests from heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation to glioma stem-like cells (GSCs). This rare tumorigenic cell subpopulation is inherently resistant to temozolomide, undergoes proneural-to-mesenchymal transition (PMT) to evade therapy, and thereby drives recurrence. Through inference of transcriptional regulatory networks (TRNs) of patient-derived GSCs (PD-GSCs) at single-cell resolution, we demonstrate how topology of transcription factor interactions drives distinct trajectories of cell state transitions of susceptible and resistant PD-GSCs in response to cytotoxic drug treatment. By experimentally testing TRN simulation-based predictions, we show that drug treatment drives surviving cells of a PD-GSC along a trajectory of intermediate states, akin to a bottleneck in gene expression space, exposing vulnerability to potentiated killing by sequential addition of siRNA or a second drug targeting transcriptional programs governing non-genetic plasticity of a PD-GSC. Thus, our findings demonstrate an approach to uncover and use TRN topology of a PD-GSC to rationally predict combinatorial and sequential treatments that block treatment escape and acquired resistance in GBM.

systems biology↗