Biology subjects

Chan, I.

Publications and source records attributed to Chan, I..

4 recordsLinked to original sources

bioRxiv2026

Structural diversification of phage tail fibres enables recognition of diverse type IV pili

Viruses must recognize receptors on host surfaces to initiate infection, but these receptors can evolve rapidly, posing a fundamental challenge to viral persistence. The type IV pilus of Pseudomonas aeruginosa is an ideal model system to study virus-receptor coevolution because its major pilin subunit PilA exhibits extensive sequence and chemical diversity while remaining essential for phage attachment. Here, we combined large-scale comparative genomics with structural and functional analyses to determine how pilus-dependent phages maintain infectivity despite extensive receptor diversification. Pilin variation was concentrated at solvent-exposed regions, altering filament surface chemistry while preserving key subunit-subunit interfaces. Despite this variation, phages recognized divergent pilins more effectively than polyclonal antisera. However, phages differed markedly in their sensitivity to receptor perturbation: some required electrostatic and structural compatibility, whereas others tolerated substantial receptor modification, including the presence of post-translational glycosylation. Comparisons of AlphaFold3 structural models revealed two distinct tail fibre architectures associated with those phenotypes. Phages encoding tail fibres with conserved receptor-binding domains were more sensitive to receptor perturbation within a given pilin background, while those with structurally diversified binding regions infected strains expressing highly divergent pilins. Together, these findings suggest that modular diversification of receptor-binding proteins provides a structural route by which phages accommodate receptor evolution. SIGNIFICANCEUnderstanding the determinants of viral host range is essential for explaining how viruses persist in the face of receptor diversification. Using pilus-dependent bacteriophages that bind diverse type IV pilins in Pseudomonas aeruginosa, we show that differences in tail fibre architecture are associated with distinct sensitivities to receptor variation. Phages with structurally conserved receptor-binding regions are sensitive to receptor perturbation, whereas those with diversified binding architectures remain infectious across strains expressing highly divergent pilins. Our results identify a structural correlate of receptor recognition breadth and reveal how receptor-binding protein architecture contributes to viral host range and adaptation. These data can inform the selection or engineering of broad-host range phages for therapeutic applications.

microbiology↗

bioRxiv2025

Periodical cicadas suffer legacy effects of century-old forest removal

Periodical cicada (Magicicada spp.) ranges have continued to decline even as their forest habitat has rebounded from historic lows. This counterintuitive trajectory may be a consequence of Magicicadas limited dispersal capabilities combined with their requirement that individual host trees survive across decades. We studied the relationship between >150 years of landscape change and brood XIII periodical cicada activity in Johnson County, IA. We found that the presence of Magicicada breeding populations was better predicted by tree cover in 1930 than by present-day tree cover, with cicadas primarily relegated to sites that did not fall below 17.4% tree cover. While total forest has increased since 1930, this is a net increase, inclusive of considerable turnover every 17 years, and cicada ranges have declined more than they have expanded. A model based on empirical measures of forest turnover and cicada dispersal distances suggests that cicada ranges will continue to decline under nearly all conditions. A managed relocation of 20,126 adult Magicicada to a restored forest failed, reinforcing that dispersal to new sites cannot be artificially accelerated to offset declines. Preservation of forest habitat across centuries may be the only bollard standing between periodical cicadas and their extinction.

ecology↗

bioRxiv2024

Mimicking the breast metastatic microenvironment: characterization of a novel syngeneic model of HER2+ breast cancer

Preclinical murine models in which primary tumors spontaneously metastasize to distant organs are valuable tools to study metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line, NT2.5-lung metastasis (- LM), that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. Within one week of orthotopic implantation of NT2.5-LM in NeuN mice, distant metastases can be observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. Metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. We demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT) and enrichment in EMT-regulating pathways, suggestive of their enhanced metastatic potential. The new NT2.5-LM model provides more rapid and spontaneous development of widespread metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses targeting distant visceral metastases SUMMARY STATEMENTWe characterize a new syngeneic, immune-competent murine model of breast cancer (NT2.5-LM) that yields rapid and widespread metastases, preserves spontaneous metastasis, and provides a model for studying novel therapeutic interventions.

cancer biology↗

bioRxiv2019

Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson’s disease

BackgroundWith spot urine collected from a large control sample of preschool children (aged 3-7 years), reference range of spot urine copper excretion indexes and their biological variation were defined.\n\nMethodsIn order to investigate their test performance in screening of Wilson disease in this age group, multiple spot urine samples from 6 WD patients diagnosed at presymptomatic stage were analysed. Cut-off values for spot urine copper concentration, copper to creatinine ratio and copper to osmolality ratio at 0.5 {micro}mol/L, 0.1 {micro}mol/mmol and 0.00085 {micro}mol/mOsmol (32 {micro}g/L, 56 {micro}g/g creatinine and 0.054 {micro}g/mOsmol, respectively, in conventional units) have potential application in differentiation of WD patients.\n\nResultsThe data provides a new insight that the inter-individual variation of spot urine copper indexes (CVg) were moderate with figures around 60% which was similar to other clinically useful urine tests, such as urine albumin excretion ratio. Spot urine copper excretion strongly correlated with both urine creatinine and osmolality. And more than 95% of data points in health preschool children fell within prediction regions by linear regression suggesting a good utility of normalisation by these 2 analytes. Receiver operator curve (ROC) showed that copper to osmolality ratio was the best index with an area under curve (AUC) greater than 0.98.\n\nConclusionsBased on the data, a new WD screening time window targeting preschool children is proposed. Application of a bivariate screening strategy using spot urine copper concentration and urine osmolality may be useful in a population screening program for preschool children.

pathology↗