Biology subjects

Choi, S.

Publications and source records attributed to Choi, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Acute social defeat induces cannabinoid type 1 receptor-dependent synaptic depression in the anterior ventral subiculum to anterior hypothalamic nucleus pathway to drive social avoidance in male mice

BACKGROUND: Social avoidance is a protective response that limits exposure to harmful social stimuli. Although avoidance is a characteristic stress phenotype, its circuit-level regulation remains unclear. The ventral subiculum (vSUB), a major hippocampal output, projects to the anterior hypothalamic nucleus (AHN), a key region for stress responses. METHODS: Male mice underwent acute social defeat stress (ASDS) or subthreshold social defeat stress. We combined social interaction, open field, and elevated plus maze testing with optogenetic-assisted slice recording, pharmacology, pathway-specific chemogenetics and optogenetics, retrograde and anterograde transsynaptic tracing, and in situ hybridization. RESULTS: ASDS induced presynaptic depression at anterior vSUB (avSUB) [->] AHN synapses through a glucocorticoid- and cannabinoid type 1 receptor (CB1R)-dependent mechanism, while posterior vSUB (pvSUB) [->] AHN synapses were unaffected. Infusing a CB1R antagonist into the AHN before ASDS attenuated both the synaptic depression and the social avoidance. Chemogenetic activation of the avSUB [->] AHN pathway during ASDS attenuated social avoidance, whereas its inhibition induced avoidance under subthreshold stress. Optogenetic activation of the avSUB [->] AHN pathway produced an immediate increase in social approach. Anterograde tracing revealed that anterior and posterior vSUB neurons project to largely separate AHN populations. The pvSUB [->] AHN pathway modulates anxiety-like behavior without altering social approach. CONCLUSIONS: These findings reveal specialized roles for vSUB subregions in social and emotional responses, and identify presynaptic gating of the avSUB [->] AHN synapse as a control point for stress-induced social withdrawal.

neuroscience↗

bioRxiv2026

Global population genomics and pangenome of the clubroot pathogen link clonal expansion and effector diversification to resistance breakdown in canola

Clubroot disease, caused by the obligate biotrophic protist Plasmodiophora brassicae, threatens Brassica crops worldwide. Novel pathogen virulence frequently breaks resistance in agricultural crops, and yet explanations for isolate evolution remain unknown. We combined whole genome sequencing of 192 isolates from 24 countries with a pangenome analysis of 55 high-quality complete or nearly complete genome assemblies and performed functional effector analyses to investigate potential mechanisms of virulence emergence. Three major phylogenetic clusters were identified, including two highly clonal lineages with contrasting virulence profiles, and a genetically diverse population retaining signatures of recombination. Our findings support a model in which genome-wide purifying selection maintained core genome integrity, while effector genes evolved under less constraint. Despite a compact closed pangenome, we identified chromosome 17 as a major hotspot of single nucleotide and structural variations, transposable elements and expansion of ankyrin repeat effectors. Within the variable chromosome 17, PbAnk2 alleles from virulent and avirulent isolates encoded proteins with distinct predicted structures. PbAnk2 interacted with the Arabidopsis co-chaperone DJC31 in yeast two-hybrid and BiFC assays, whereas co-immunoprecipitation did not detect an interaction for the allele found in isolates that break CRa-mediated resistance, suggesting that allelic variation may alter PbAnk2's association with DJC31. These findings reveal the clonal expansion of virulent isolates and connect it to effector diversification that led to resistance breakdown and establish a genomic framework for pathogen surveillance and durable clubroot resistance.

genomics↗

bioRxiv2026

IL-2 and CD40L can establish and sustain a human B cell-mediated immune regulatory network

B cells can control inflammation, but the factors governing B cell-mediated immune regulatory network remain unclear. We report that IL-2/CD40L enable class-switched memory (CSM) B cells to acquire an immunosuppressive phenotype characterized by the expression of surface TIGIT as well as multiple other inhibitory receptors (PD-1, LAG-3, GITR, CD39, and CTLA-4) and soluble molecules (IL-10, granzyme B, and IL-35). TIGIT+ CSM B cells expressing functional CCR9 exhibit significant defects in total immunoglobulin secretion, while preserving IgA2 secretion. Furthermore, IL-2/CD40L-induced ex vivo-generated TIGIT+ CSM B cells suppress human T cell-mediated inflammation in a xenogeneic mouse model of acute graft-versus-host disease, while promoting IL-10-producing regulatory T cell (Treg) response. These findings identify IL-2/CD40L as key drivers of a B cell-mediated immune regulatory network, especially by generating TIGIT+ CSM B cells that can further promote Treg response. This study supports the development of TIGIT+ B cell-based therapy models for inflammatory diseases.

immunology↗

bioRxiv2026

The Arabidopsis outward K+ channel GORK mediates flg22-induced K+ efflux and stomatal closure

Transient K+ efflux occurs rapidly following pathogen-associated molecular pattern (PAMP) perception by pattern recognition receptors (PRRs) as part of pattern-triggered immunity (PTI). However, the molecular identities of the K+ channels responsible for PTI-associated K+ efflux and the mechanisms linking immune signaling to K+ channel regulation remain largely unknown. Here, we show that the channel GUARD CELL OUTWARD RECTIFYING K+ (GORK) is required for K+ efflux and stomatal closure induced by flg22, a model PAMP derived from bacterial flagellin. BOTRYTIS-INDUCED KINASE 1 (BIK1), a receptor-like cytoplasmic kinase associated with immune receptor complexes that functions as a central regulator of PTI, interacts with GORK and phosphorylates the channel on the conserved T199 residue in vitro. Electrophysiological analyses indicate that BIK1 inhibits GORK activity in a kinase-dependent manner and that T199 plays an essential role for GORK function. Together, this study identifies GORK as the key K+ channel executing rapid PTI-associated K+ efflux and associated stomatal closure, thus shedding light on the mechanisms of early immune signaling.

plant biology↗

bioRxiv2026

Therapeutic AIBP expression contributes to synaptic preservation and vision restoration against glaucomatous neuroinflammation

Lowering intraocular pressure (IOP) is the only approved treatment for glaucoma, yet retinal ganglion cell (RGC) degeneration and vision loss often progress despite reducing IOP. Apolipoprotein A-I binding protein (AIBP) stabilizes ATP-binding cassette subfamily A member 1 (ABCA1) and promotes cholesterol efflux, thus controlling cholesterol-rich lipid rafts and restraining lipid raft-dependent Toll-like receptor 4 (TLR4) inflammatory signaling. Here we show that AAV2-mediated expression of human AIBP (hAIBP) preserves inner retinal synaptic integrity and visual function in experimental glaucoma without altering IOP. In DBA/2J mice, a single intravitreal injection of AAV2-hAIBP at 5 months protected RGCs and preserved pattern electroretinogram and pattern visual evoked potential responses at 10 months, even though IOP was indistinguishable from empty-vector controls. AAV2-hAIBP preserved CaMKII and synapsin phosphorylation, restored synaptophysin and PSD95 in the inner plexiform layer, and reduced the expression of TLR4, complement C1q, IBA1, IL-1b, and IL-6 induction in Muller glia and microglia. Comparable protection was observed in microbead-induced ocular hypertension in C57BL/6 mice, both when the AAV2-hAIBP was delivered before microbead injection and when it was delivered after IOP elevation was established. Elevated IOP reduced endogenous retinal AIBP and ABCA1 expression, and AAV2-hAIBP restored both. Protection required the TLR4-binding domain, as an AIBP mutant lacking this domain failed to preserve RGCs. Conversely, AIBP knockout retinas exhibited increased CaMKII phosphorylation and reduced synaptophysin in the absence of elevated IOP. These findings identify synaptic preservation through the AIBP-TLR4 axis as an IOP-independent therapeutic mechanism and support AAV2-hAIBP as a candidate gene therapy for glaucoma.

neuroscience↗

bioRxiv2026

A synaptic wiring diagram underlying modality-specific ascending pathways of the superficial spinal dorsal horn

The spinal cord dorsal horn transforms tactile, thermal, pruritic, and nociceptive signals from peripheral somatosensory neurons into outputs to the brain, but how dorsal horn circuits organize diverse inputs into modality-selective ascending pathways is poorly understood. Using dSC1, a large-scale electron microscopy dataset of the mouse dorsal horn, we mapped the circuitry connecting primary sensory afferents to projection neurons of the anterolateral tract (ALT), a principal pathway conveying somatosensory information to the brain. We find that afferents encoding distinct modalities are routed onto connectivity-defined populations of ALT projection neurons. Nociceptors and cold thermoreceptors directly innervate distinct lamina I ALT projection neuron populations specialized for conveying noxious and cooling signals, respectively, whereas tactile and pruritic signals instead pass through a recurrent, multilayered network involving interneurons called vertical cells before reaching a separate ALT projection population. This distinction, direct versus polysynaptic wiring, underlies marked differences in sensory convergence and establishes segregated ascending channels for conveying signals encoding the principal somatosensory modalities. Together, our findings define an architectural logic by which the dorsal horn integrates and routes tactile, thermal, pruritic, and nociceptive information into distinct ALT output pathways to the brain.

neuroscience↗

bioRxiv2026

Synthetic genetic circuits that count developmental cues in plant roots

Plants explore soil environments through their roots, which branch repeatedly to access water and soil-borne nutrients. In many plants, root branches are generated by repeated developmental programs and molecular analyses have not identified markers that distinguish primary from later root branches. Consequently, efforts to engineer plant roots for improved water or nutrient acquisition are limited to changes that affect the entire root system. Here, we developed synthetic genetic circuits to count repeating root development cues and enable differential gene expression in successive root branches of the model plant Arabidopsis thaliana. The circuits use a root primordium-specific promoter to express large serine recombinases, which irreversibly invert segments of DNA each time a new lateral root is initiated. This converts repeating rounds of root formation into distinct, heritable DNA states. Because root branch specification and outgrowth occur over a ~2 day period, we tested circuit designs for their ability to count long-duration input pulses and developed an architecture that produces distinct fluorescence outputs in primary, secondary, and tertiary roots. By linking repeated developmental cues to distinct genetic outputs, synthetic genetic circuits that count enable root system engineering at the resolution of individual branches and offer a general strategy for dissecting developmental processes that rely on repeated signals.

bioengineering↗

bioRxiv2026

Decoding subtype development and function in human pluripotent stem cell-derived midbrain dopaminergic neurons

Midbrain dopaminergic (mDA) neurons comprise molecularly and functionally distinct subtypes with differential vulnerability in neurodegenerative and psychiatric disorders. However, the mechanisms specifying subtype identity remain poorly understood, and protocols for the selective derivation of human mDA subtypes are lacking. Here we establish a strategy to derive substantia nigra (A9) and ventral tegmental area (A10) mDA neurons from human pluripotent stem cells (hPSCs). A9 identity is specified by dual-SMAD activation through Activin A and BMP7 at the midbrain floor-plate progenitor stage, whereas A10 identity is promoted by BMP inhibition. A9 mDA neurons are purified based on ALDH1A1 expression, and subtype identity is maintained by continued TGF-{beta} modulation and ESRRB activation in vitro and upon transplantation in vivo. Single-cell RNA sequencing and biochemical analyses demonstrate that hPSC-derived A9 neurons exhibit increased oxidative phosphorylation, neuromelanin-like pigmentation, elevated dopamine synthesis and release, and electrophysiological properties characteristic of A9 mDA neurons in vivo. Integration with human fetal midbrain datasets confirms strong transcriptional concordance between in vitro-derived and in vivo mDA subtypes. Neuromelanin-like structures produced by hPSC-derived A9 neurons trigger pro-inflammatory cytokine secretion from hPSC-derived microglia, and A9 neurons are primed to upregulate MHC-I genes in response to interferon-{gamma}, features which may contribute to the selective vulnerability of A9 neurons. Together, these results establish a robust in vitro platform to interrogate human mDA subtype development, function, and selective vulnerability, enabling mechanistic studies relevant to Parkinson's disease and the development of cell-based therapies.

developmental biology↗

bioRxiv2026

The Impact of TOR-S6K-eIF5A Signaling on Translational Control is Key to Plant Root Development

Nutrient-responsive Target of Rapamycin (TOR)-S6 kinase (S6K) signaling coordinates plant growth with protein synthesis, but how it interfaces with translation elongation to produce specific developmental outputs remains unclear. Here, we identify eukaryotic translation factor 5A (eIF5A) as an S6K-associated phosphoprotein in Arabidopsis thaliana. S6K1 and S6K2 associate with all three eIF5A isoforms and phosphorylate them in vitro, with Ser2 emerging as the major S6K1-responsive site in eIF5A-2. The corresponding N-terminal serine is invariant across the analyzed Archaeplastida eIF5A proteins. Conditional depletion of TOR, S6K1/2, or eIF5A produces overlapping reductions in primary root length and root hair coverage. eIF5A depletion leaves bulk protein synthesis and polysome profiles largely unchanged while selectively decreasing output from deca-proline reporters. Reporter activity is restored by amiRNA-resistant wild-type and phosphomimetic S2D eIF5A-2, whereas S2A does not restore activity, demonstrating the functional importance of the Ser2 state. Proteomic profiling identifies a restricted set of eIF5A-responsive proteins, and five of six tested insertion mutants display altered primary root growth, root hair coverage, or both. Together, these findings uncover a regulatory connection between S6K and eIF5A and establish eIF5A-dependent selective translation as a mechanism contributing to root development in A. thaliana.

molecular biology↗

bioRxiv2026

Structural Determinants of Synaptic Vesicle Protein 2C Ligand Selectivity and Their Impact on Dopamine Release

The synaptic vesicle protein 2 (SV2) family is a highly conserved group of transmembrane glycoproteins sharing approximately 70% sequence identity. SV2A and SV2B are broadly distributed throughout the brain, while SV2C, the evolutionarily oldest member of the family, is primarily found in dopaminergic brain regions in the basal ganglia. Genome-wide association studies have linked SV2C to Parkinson's disease, and SV2C appears to enhance dopamine storage in synaptic vesicles, but the basis for this effect is unknown. SV2s are the target of the racetam class of antiseizure medications, and SV2A-specific ligands are widely used to treat seizures. Recently several SV2C-specific ligands have been developed, but the structural basis for ligand specificity is unclear. A better understanding of SV2C structure, function, and pharmacology could lead to better targeted therapies for epilepsy, Parkinson's disease, and other dopamine-related conditions. Here we present cryo-EM structures of apo SV2C, SV2C bound to the high affinity non-selective SV2 ligand padsevonil, SV2C bound to the SV2C-selective ligand UCB-F, and SV2A bound to the SV2A-selective ligand plosaracetam (also known as ABBV-552/SDI-118). We find that SV2C has a wider luminal opening than SV2A and SV2B, which allows for UCB-F to bind to the primary site and form favorable interactions that are not possible in the narrower primary binding site of SV2A and SV2B. We also demonstrate that UCB-F and padsevonil, but not plosaracetam, reduce dopamine release in striatal sections of mouse brain. Our biochemical experiments and structures provide insights into SV2 ligand specificity and offer a template for the rational development of therapeutics targeting SV2C.

biochemistry↗

bioRxiv2026

Processing strategies for improving cortical thickness correspondence between low-field and high-field MRI in young people

Portable low-field MRI systems are a promising complement to conventional high-field systems, enabling broader access to MRI. However, correspondence in cortical thickness estimates between low- and high-field MRI in young people remains limited despite its importance for neurodevelopment and psychopathology. To evaluate how multiple low-field image processing approaches improve cortical thickness correspondence with high-field MRI in a large sample of young individuals, we collected T1-weighted (T1w) and T2-weighted (T2w) data using both low-field (64mT) and high-field (3T) MRI within one week of each other from a community sample of young people. We applied deep learning-based super-resolution methods (SynthSR v1 and SynthSR v2) followed by recon-all, or other reconstruction methods (recon-all-clinical and recon-any), to low-field data acquired across multiple sequences (T1w and T2w) and orientations (axial, coronal, sagittal, and multi-orientation average), with and without resampling and/or co-registration. We assessed global, lobar, and regional cortical thickness correspondence with 3T MRI measures based on the Desikan-Killiany atlas using Pearson and intraclass correlations. We compared pipelines using Steiger's Z-tests and Fisher's Z-tests. A total of 150 individuals (mean age, 18.63+/-5.07; 80 female) were included. We observed the highest global correspondence with recon-all-clinical applied to coronal T1w images (r=0.40, pFDR=3.02e-05), which significantly exceeded the best global correspondence in our previous study (Fisher's Z=1.99, p=0.047). At the lobar and regional levels, multi-orientation T2w images processed with recon-all-clinical showed the highest correspondence across the greatest number of regions (4/12 lobes; 13/68 regions). This pipeline showed the highest correspondence and largest improvements relative to recon-all alone in frontal, cingulate, and temporal regions, including the right pars triangularis (r=0.52, pFDR=4.78e-11; Steiger's Z=4.78, pFDR=4.25e-06), right caudal anterior cingulate (r=0.47, pFDR=3.83e-09; Steiger's Z=5.46, pFDR=1.32e-07), and left parahippocampal regions (r=0.58, pFDR=2.98e-14; Steiger's Z=5.17, pFDR=6.01e-07). We observed significantly improved cortical thickness correspondence in low-field MRI in young people relative to recon-all alone and our prior work. The recon-all-clinical pipeline yielded moderate correspondence, particularly in frontal, cingulate, and temporal regions. Our results demonstrate a methodological improvement in the use of low-field MRI for assessing cortical thickness in young people, providing a quantitative benchmark for current tools in this area.

neuroscience↗

bioRxiv2026

Human meningiomas arise from developmental meningeal mosaicism

Meningioma is the most common primary intracranial tumour, yet its genetic origin and the temporal sequence of mutational events remain poorly defined. Here, we analysed 80 triple-matched tumour, histologically normal meninges, and blood samples from 22 patients. NF2 or TRAF7 driver mutations are detectable in phenotypically normal meninges in 81.8% of cases (95% CI: 59.7-94.8%; VAF [~]0.02%), corroborated by high-depth sequencing, single-cell cloning, and phylogenetic analysis. By distinguishing developmental mosaic mutations from postnatal tumour-private mutations, we revealed distinct mutational signatures and resolved the temporal sequence of meningioma evolution. The developmental origin was further underscored in patients with multiple meningiomas, where identical driver mutations were shared across genomically distinct tumours and meninges, and in intraventricular meningiomas (IVM), where driver mutations were detected in distant cranial dura. Reconstruction of mutational timing revealed lineage-specific trajectories, linking mosaicism to diverse disease presentations including solitary meningioma, IVM, meningiomatosis, and NF2-related schwannomatosis. Together, these findings reveal an early origin of human meningioma, in which developmental mosaicism establishes a pre-neoplastic field within the meninges, providing a developmental framework for adult tumourigenesis.

Cancer Biology↗

bioRxiv2026

Directional bone matrix mineralization in the CAM assay is governed by vascular integration and matrix remodeling

Bone matrix mineralization plays an important role in maintaining bone health but is a highly dynamic process for which few physiologically relevant model systems exist. The chorioallantoic membrane (CAM) assay is one such assay and has been used to study biomineralization; however, the mechanisms controlling mineral deposition in the CAM assay remain poorly understood. Here, we implanted decellularized, organic bone matrices onto the CAM and investigated their mineralization using a combination of micro-computed tomography, Raman spectroscopy, scanning electron microscopy, and histochemistry. These studies revealed increased mineralization and microvessel density on the shell-facing interface of the implanted matrices, while their embryo-facing counterpart lacked mineralization but was densely infiltrated by cells. Seeding organic bone matrices with mesenchymal stromal cells (MSCs) prior to CAM-implantation prevented mineralization by altering matrix micro- and nanostructure and limiting vessel integration. Collectively, our results suggest that mineral precursors from the eggshell and vasculature combine to mineralize organic bone matrix in the CAM assay, while proteolytic remodeling by invaded or implanted stromal cells inhibits that process. Our findings provide critical new insights into the interplay between acellular and cellular drivers of bone matrix mineralization, and will inform future studies of biomineralization using the CAM assay.

bioengineering↗

bioRxiv2026

Mutational and functional heterogeneity of homology-directed repair deficiency and clinical implications

Homology-directed repair deficiency (HRd) encompasses mutations in multiple genes yet is treated clinically as a single entity. Here, through parallel analyses of isogenic knockouts of multiple HR pathway genes, integrating multi-omic analyses with genome-wide CRISPR-Cas9-dependency and resistance screens, we show that HRd is not a single entity but exists along a molecular and functional continuum. BRCA1, BRCA2, PALB2, RAD51C, and RAD51D mutants shared many HRd-associated mutational signatures, while RAD51B, BRIP1, CDK12 exhibited distinct genomic patterns. Functional heterogeneity was equally apparent: synthetic lethal interactions including CIP2A and a novel dependency on PRDX1 were penetrant across most HRd genotypes, whereas FANCM dependency was linked to HRd subtypes characterized by tandem duplications. PARPi resistance screens in distinct HRd contexts uncovered BRIP1 and RECQL5 as new BRCA2-specific resistance genes. HRd is thus a complex continuum, underscoring why modernizing the molecular taxonomy utilizing all genomic features available per patient is crucial to informing precision interventions.

genomics↗

bioRxiv2026

Reversion mutations define minimal BRCA1/2 requirements for therapy resistance

Although platinum salts or PARP inhibitors are effective in delivering anti-tumor responses in people with BRCA1 or BRCA2 mutated cancers, drug resistance is common and is often caused by secondary BRCA1/2 reversion mutations that restore function. By collating and analyzing 848 BRCA1/2 reversion mutations in 384 cancer patients with drug resistance, we confirm that pathogenic BRCA1/2 mutation type influences the acquisition of reversions, and that large BRCA1/2 deletions are an underappreciated form of reversion. Integrating reversion data with systematic CRISPR-Cas9 screens that delete BRCA1/2 exons, we also show that both proteins contain privileged domains whose structure is essential for drug resistance, including the PALB2 interacting domains of both BRCA1 and BRCA2. Reversions in PALB2 also conserve both BRCA1 and BRCA2 binding domains. Surprisingly, exon 11 of BRCA2, which encodes BRC repeats 1-8, is not essential for resistance. Using this patient and functional information, we estimate the likelihood of pathogenic BRCA2 mutations to revert. We show that risk of reversion correlates with both the presence of clinical reversions and the response to treatment, suggesting that the propensity to revert could be a useful clinical parameter.

cancer biology↗

bioRxiv2026

Cortical vasodynamics exhibit multiscale propagation structure in the awake mouse

Spontaneous vasomotor rhythms and fluctuations are recognized contributors to functional MRI (fMRI) signals. Yet the spatial evolution of vasomotor contributions, which bear on the interpretation of fMRI signals in terms of functionally connected brain regions, remains unresolved. To clarify this issue, we analyze the 0.01 - 0.20 Hz space-frequency modes of 14T cerebral blood volume (CBV)-weighted fMRI across the awake mouse cortex. High-resolution CBV-fMRI identified single-vessel-aligned, frequency-specific modes of vasodynamic propagation, and ultra-fast CBV-fMRI enabled mapping of phase-gradients along tangential and radial axes. Tangential gradients extended maps of vasomotor traveling waves across the entire cortical mantle, with a median speed of 0.9 - 1.3 mm/s. Radial gradients revealed approximately three-fold slower changes in timing that support lamina-dependent regulation of perfusion. Region-specific differences in propagation speed and direction occur across cortical areas and between mice. These findings reframe vascular fluctuations as a feature of brain-wide physiology, as opposed to residual noise.

neuroscience↗

bioRxiv2026

Landscape-scale navigation unlocks antibody CDR structural logic for AI-guided rescue and therapeutic optimization

While AI offers transformative potential for therapeutic antibody design, the lack of ground-truth data fundamentally constrains our ability to model the epistatic topology of fitness landscapes. Here, we establish a high-throughput workflow to characterize tens of thousands of antibody variants per week with gold-standard biophysical precision. By combinatorially assembling functional variants from deep mutational scanning, we charted antibody fitness landscapes comprising over 17,000 data points, which revealed an extremely rugged, non-navigable epistatic topology. Yet, navigating at this unprecedented scale enabled the discovery of rare peak clusters exhibiting simultaneous enhancements in affinity and productivity. Strikingly, ProteinMPNN predicted the CDR-dependent productivity landscape with remarkable accuracy, suggesting that sequence-structure compatibility within CDRs gates cellular productivity. This insight enabled a structure-guided rescue strategy combining AlphaFold3 and ProteinMPNN, which successfully restored the cellular productivity of high-affinity, low-productivity clones via single amino acid substitutions. Two elite variants drawn directly from peak clusters further demonstrated 20- to 100-fold in vivo efficacy gains in a murine psoriasis model. Our findings establish CDR structural fitness as a fundamental determinant of antibody cellular productivity and validate landscape-scale navigation as a powerful framework for therapeutic antibody optimization.

bioengineering↗

bioRxiv2026

High-variance phenome database reveals important roles of WD40 proteins in the plant pathogenic fungus Fusarium graminearum

WD40 is a highly conserved protein domain in eukaryotes, playing a critical role in various cellular process. We conducted genome-wide functional analysis of WD40 genes in Fusarium graminearum-a phytopathogenic fungus that causes severe yield loss and mycotoxin contamination in major cereal crops. Comprehensive phenome analysis of 119 WD40 gene deletion mutants across 22 distinct phenotypic traits revealed phenotypic divergence within the phenome, establishing a strong correlation between virulence and sexual reproduction. Notably, 21 core WD40 genes were identified, offering valuable insights into divergent biological processes. Pilot interactome studies of Fgwd101 and Fgwd133 provided further insights into their potential pathobiological functions. Our investigation contributes to broadening our knowledge of the biological mechanisms underlying fungal pathogenesis and may assist in the identification of targets for antifungal agents.

molecular biology↗