Biology subjects

Adebiyi, A.

Publications and source records attributed to Adebiyi, A..

3 recordsLinked to original sources

bioRxiv2025

Identification and characterization of host-modulating effectors encoded by the Cluster F1 mycobacteriophage NormanBulbieJr

NormanBulbieJr (NBJ) is a temperate siphovirus isolated on the host Mycobacterium smegmatis mc2155 that encodes 102 gene products, 60 of which have no known function (NKF). Based on gene content, NBJ is classified as a Cluster F, Subcluster F1 phage and shares 70% of its encoded gene phamilies with Girr, another F1 mycobacteriophage that was recently analyzed in a genome-wide overexpression screen and found to encode 29 diverse gene products capable of inhibiting growth of M. smegmatis. Similar functional screens in other mycobacteriophages have uncovered a growing repertoire of diverse, phage-encoded bacterial growth inhibitors, providing prime candidates for dissecting novel bacterial-phage interactions. An arrayed overexpression library encoding all 102 genes was constructed and systematically screened using a plate-based cytotoxicity assay, identifying 29 genes that inhibit mycobacterial growth. Because mycobacteriophage genomes are also known to encode systems involved in phage-phage competition, we conducted additional phage defense assays for a subset of NBJ genes in our library. This analysis confirmed homotypic immunity by the predicted immunity repressor and identified gp45 as a second defense factor that protects against Cluster F phages and promotes NBJ lysogen stability. Additional mechanistic analyses indicate that gp45 functions in a secretion-dependent manner, acting after phage adsorption to reduce productive infection and early phage transcript accumulation. Escape mutant and bacterial two-hybrid analyses implicate Cluster F tape measure proteins as the likely target of gp45, consistent with disruption of an early step in phage genome delivery. Finally, we extended our analysis to explore the essentiality of all identified host-modulating genes in the NBJ life cycle, using CRISPR-enhanced recombineering to generate phage deletion mutants, revealing two host modulators that are critical for lytic growth. Conducted as part of the SEA-GENES undergraduate research consortium, this study adds to a growing functional genomics resource and provides new insights into the complex interactions between phage gene products and the mycobacterial host cell.

microbiology↗

bioRxiv2025

Enhanced PIEZO1 Function Contributes to the Pathogenesis of Sickle Cell Disease

Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the {beta}-globin gene, is characterized by sickle erythrocytes that are prone to hemolysis, causing anemia and vaso-occlusion crises. In sickle erythrocytes, hemoglobin aggregation is followed by altered cation permeability and subsequent dehydration. Interventions to restore cation permeability can decrease hemolysis and ameliorate the symptoms associated with SCD. PIEZO1 is a non-selective mechanosensitive cation channel that regulates erythrocyte volume. Gain-of-function (GOF) mutations in PIEZO1 cause hemolytic anemia by increasing cation permeability, leading to erythrocyte dehydration in humans and mice. Although PIEZO1 plays a key role in erythrocyte homeostasis, its role in SCD remains unknown. Here, we demonstrate that the function of the PIEZO1 channel is upregulated in sickle erythrocytes of humans and mice, and this enhancement can be restored through a dietary intervention. We found that PIEZO1 function in sickle erythrocytes resembles that of the GOF mutation causing hemolytic anemia. A diet enriched in the{omega} -3 fatty acid eicosapentaenoic (EPA) acid decreases PIEZO1 function in sickle erythrocytes and hemolysis in a mouse model of SCD. Furthermore, EPA decreases hemolysis and reduces inflammatory markers. We propose that PIEZO1 contributes to the increase in nonselective cationic conductance (i.e., Psickle), which leads to dehydration downstream of hemoglobin polymerization. Our results suggest that reducing PIEZO1 function is a promising therapeutic approach to reestablishing normal cation permeability in SCD.

physiology↗

bioRxiv2024

Bond strength between receptor binding domain of spike protein and human angiotensin converting enzyme-2 using machine learning.

The spike protein (S-protein) of SARS-CoV-2 plays an important role in binding, fusion, and host entry. In this study, we have predicted interatomic bond strength between receptor binding domain (RBD) and angiotensin converting enzyme-2 (ACE2) using machine learning (ML), that matches with expensive ab initio calculation result. We collected bond order result from ab initio calculations. We selected a total of 18 variables such as bond type, bond length, elements and their coordinates, and others, to train ML models. We then trained five well-known regression models, namely, Decision Tree regression, KNN Regression, XGBoost, Lasso Regression, and Ridge Regression. We tested these models on two different datasets, namely, Wild type (WT) and Omicron variant (OV). In the first setting, we used 90% of each dataset for training and 10% for testing to predict the bond order. XGBoost model outperformed all the other models in the prediction of the WT dataset. It achieved an R2 Score of 0.997. XGBoost also outperformed all the other models with an R2 score of 0.9998 in the prediction of the OV dataset. In the second setting, we trained all the models on the WT (or OV) dataset and predicted the bond order on the OV (or WT) dataset. Interestingly, Decision Tree outperformed all the other models in both cases. It achieved an R2 score of 0.997.

biophysics↗