Biology subjects

Lee, Y.-W.

Publications and source records attributed to Lee, Y.-W..

3 recordsLinked to original sources

bioRxiv2026

Transcriptome dissection of the Zeb2-associated network reveals a role for NRPS15 in zearalenone biosynthesis in Fusarium graminearum

Fungal secondary metabolites, including mycotoxins, play important roles in fungal biology and represent major concerns for food and feed safety. Zearalenone (ZEA) is an estrogenic polyketide mycotoxin produced by several Fusarium species, yet the genetic network governing its production remains poorly characterized. Here, we investigated genes associated with ZEA production in Fusarium graminearum using two complementary transcriptomic approaches. Time-resolved transcriptome analysis revealed transcriptional changes preceding detectable ZEA accumulation. Temporal clustering further revealed coordinated changes in primary metabolism, transcriptional regulation, carbohydrate utilization, and stress- and transport-associated pathways during ZEA-inducing cultivation. Genotype-based transcriptome analysis of ZEB2 deletion and overexpression strains subsequently identified Zeb2-responsive genes. Functional screening identified NRPS15, encoding a previously uncharacterized nonribosomal peptide synthetase-like protein adjacent to the ZEA biosynthetic cluster, as an important contributor to ZEA production. Deletion of NRPS15 markedly reduced ZEA production and expression of PKS4, PKS13, ZEB1, and ZEB2. NRPS15 expression did not restore ZEA production in the absence of Zeb2. NRPS15 orthologs were conserved in several ZEA-producing Fusarium species, and deletion of NRPS15 substantially reduced ZEA production in Fusarium culmorum. These findings expand the functional genetic context of ZEA production beyond the canonical four-gene biosynthetic cluster.

molecular biology↗

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↗

bioRxiv2020

Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment

Acute lung inflammation has severe morbidity, as seen in COVID-19 patients. Lung inflammation is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries ("margination"). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted an in vivo screen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g. viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema arising in lung inflammation. Finally, we demonstrate that ischemic ex vivo human lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections.

bioengineering↗