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Biomedical subjects

Bing Wang

Publications and source records attributed to Bing Wang.

6 recordsLinked to original sources

Strigolactones constrain rice drought acclimation by suppressing ROS scavenging through the D53-OsWRKY31-ZFP36 module.

Strigolactones (SLs) are a class of plant hormones essential for tiller development and yield under diverse environmental conditions. Drought is a major limiting factor for rice yields. Although SLs contribute to drought resistance, mechanisms and practical applications of SL pathway in drought acclimation of rice remain poorly understood. Our study shows that short-term dehydration represses SL biosynthesis in rice roots. Genetic assays indicate that disruption of SL biosynthesis or signaling elevates rice drought resistance, whereas SL signaling activation or supplementation with the SL analog GR244DO impairs drought resistance. SLs negatively regulate drought acclimation by promoting degradation of the repressor protein DWARF53 (D53). D53 interacts with the transcription factor OsWRKY31 via its N-terminal domain and suppresses the protein level of OsWRKY31, which binds to and represses transcription of the ZFP36 promoter. ZFP36 encodes a zinc-finger transcription factor that promotes H2O2 scavenging to sustain reactive oxygen species (ROS) homeostasis during drought stress. Notably, the drought-resistant upland rice variety IRAT109 exhibits lower SL levels in root exudates than the lowland rice variety Nipponbare (NP). Genome editing of key components in SL pathway enhances drought resistance in NP, Huazhan (HZ), and IRAT109. The agronomic potential of tuning SL biosynthesis is further supported by the elite D17/HTD1 allele, which weakens SL biosynthesis and improves drought resistance and grain yield in Nekken 2 (NK2) under field conditions. These findings uncover a key mechanism underlying SL-repressed drought acclimation in rice and provide an effective strategy to improve drought resistance in diverse rice varieties amid ongoing climate change.

D53

Structural basis of sex pheromone detection in aphids.

Sex pheromones play a central role in regulating animal behavior and reproduction. In insects, these signals are perceived through specialized odorant receptors (ORs) that mediate species-specific communication and safeguard genetic integrity. However, the structural basis of sex pheromone detection remains largely unresolved. Here, we identified two ORs in the pea aphid Acyrthosiphon pisum, along with the conserved OR co-receptor (Orco), which together mediate recognition of the pheromone components nepetalactone and nepetalactol. Functional assays demonstrated that ApOR21-Orco and ApOR22-Orco specifically respond to nepetalactol and nepetalactone, respectively. Using cryo-electron microscopy, we resolved the structure of the ApOR22-Orco complex in three states - unbound closed, nepetalactone-bound closed, and nepetalactone-bound open - revealing a heterotetrameric ion channel formed by one ApOR22 and three ApOrco subunits. Ligand binding to ApOR22 triggers conformational rearrangements that induce asymmetric pore dilation, thereby enabling ion conduction. Together, these results provide a mechanistic framework for understanding sex pheromone perception in insects and establish a structural foundation for the rational development of environmentally sustainable pest-control strategies.

Animals

Selective targeting of a histone-like silencer Sfx to the R6K conjugal transfer operon.

Conjugative plasmids drive bacterial evolution and antibiotic resistance spread, yet their gene expression must be silenced to protect the host. A histone-like protein H-NS represses many mobile and sedentary xenogenes but fails to silence the conjugal transfer vir operon of R6K, a prototype IncX plasmid. Instead, R6K encodes its own H-NS homolog, Sfx, to repress the vir operon. Here, we show that, unlike other plasmid silencers that target promoters, Sfx cooperates with Rho factor to arrest transcription elongation. ChIP-seq reveals that Sfx and H-NS share similar DNA motifs and a preference for negative supercoiling, but occupy reciprocal genomic niches; Sfx is enriched on the R6K vir operon despite weak chromosomal binding, whereas H-NS displays the opposite preference. We show that Sfx binding to vir DNA critically depends on DNA topology and hypothesize that its selective targeting to R6K is mediated by Sfx-vir interactions and phase separation. Our results suggest that Sfx phase separates with R6K to ensure its preferential recruitment to the plasmid DNA and forms stable bridged nucleoprotein filaments that are impermeable to competitors such as H-NS. These findings reveal how histone-like proteins can partition the genome into distinct regulatory niches, a strategy likely mirrored across all life.

Operon

Label-free structural imaging of plant roots and microbes using third-harmonic generation microscopy.

Root biology is pivotal in addressing global challenges including sustainable agriculture and climate change. However, roots have been relatively understudied among plant organs, partly due to the difficulties in imaging root structures in their natural environment. Here we used microfabricated ecosystems (EcoFABs) to establish growing environments with optical access and employed nonlinear multimodal microscopy of third-harmonic generation (THG) and three-photon fluorescence (3PF) to achieve label-free, in situ imaging of live roots and microbes at high spatiotemporal resolution. THG enabled us to observe key plant root structures including the vasculature, Casparian strips, dividing meristematic cells, and root cap cells, as well as subcellular features including nuclear envelopes, nucleoli, starch granules, and putative stress granules. THG from the cell walls of bacteria and fungi also provides label-free contrast for visualizing these microbes in the root rhizosphere. With simultaneously recorded 3PF signal, we demonstrated our ability to investigate root-microbe interactions by achieving single-bacterium tracking and subcellular imaging of fungal spores and hyphae in the rhizosphere.

Plant Roots

FTDC1/2, oocyte-specific cofactors of DNMT1 required for epigenetic regulation and embryonic development.

The unique epigenetic patterns during gametogenesis and embryonic development indicate the existence of specialized methylation machinery. In the present study, we describe the discovery of two oocyte-specific cofactors of DNA methyltransferase 1 (DNMT1), encoded by uncharacterized genes, ferritin domain containing 1 and 2 (Ftdc1 and Ftdc2). Genetic ablation of Ftdc1 or Ftdc2 causes midgestation defects and female infertility. FTDC1 or FTDC2 depletion induces the progressive loss of DNA methylation including imprinted regions in early embryos. This loss correlates with a marked reduction in DNMT1 protein due to increased degradation, likely via the ubiquitin-proteasome pathway. Mechanistically, we find that FTDC1, FTDC2 and DNMT1 form a complex by direct interactions, thereby stabilizing each other. Surprisingly, knockout of Ftdc1 or Ftdc2 displayed stronger DNA demethylation phenotypes and earlier embryonic lethality than the Dnmt1-null mutant, implying their unique functions. These data suggest that FTDC1/2 are crucial players specifically involved in maintaining genomic methylation during embryogenesis, offering new insights into the epigenetic control of mammalian development.

DNA (Cytosine-5-)-Methyltransferase 1

Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.

Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a rational design strategy. AAV2.5 was generated from the AAV2 capsid with five mutations from AAV1. The novel chimeric vector combines the improved muscle transduction capacity of AAV1 with reduced antigenic crossreactivity against both parental serotypes, while keeping the AAV2 receptor binding. In a randomized double-blind placebo-controlled phase I clinical study in DMD boys, AAV2.5 vector was injected into the bicep muscle in one arm, with saline control in the contralateral arm. A subset of patients received AAV empty capsid instead of saline in an effort to distinguish an immune response to vector versus minidystrophin transgene. Recombinant AAV genomes were detected in all patients with up to 2.56 vector copies per diploid genome. There was no cellular immune response to AAV2.5 capsid. This trial established that rationally designed AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective (e.g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer.

Amino Acid Sequence