Biology subjects

Baskaran, D. K. K.

Publications and source records attributed to Baskaran, D. K. K..

3 recordsLinked to original sources

bioRxiv2025

Mapping Structural Constraints and Adaptive Potential in a Capsule-Degrading Phage Tailspike Protein

Bacteriophage tailspike proteins (TSPs) degrade bacterial capsules to enable infection, yet the molecular determinants of their function and host range remain unclear. We applied deep mutational scanning (DMS) to the endosialidase TSP of Escherichia coli K1 phage K1F, generating 22,365 single-amino-acid variants using an enhanced ORACLE phage engineering platform. Functional scores revealed the TSP is structurally fragile yet harbors pockets of adaptive flexibility. Mutations within the {beta}-propeller active site uncovered residues accommodating longer sialic acid chains than captured by structural studies, while the {beta}-helix stalk emerged as an adaptive "tuning knob" modulating processivity and specificity. Comparative selections across K1 strains identified discrimination hotspots in {beta}-barrel loops and distal residues outside canonical binding sites, implicating capsule modifications and O-antigen presence as key modulators of host range. By resolving how specific mutations modulate function and host range, this study offers a roadmap for designing phages that overcome capsule-based defenses in pathogenic bacteria.

biochemistry↗

bioRxiv2024

FROG Analysis Ensures the Reproducibility of Genome Scale Metabolic Models

Genome-scale metabolic models (GEMs) and other constraint-based models (CBMs) play a pivotal role in understanding biological phenotypes and advancing research in areas like metabolic engineering, human disease modelling, drug discovery, and personalized medicine. Despite their growing application, a significant challenge remains in ensuring the reproducibility of GEMs, primarily due to inconsistent reporting and inadequate model documentation of model results. Addressing this gap, we introduce FROG analysis, a community-driven initiative aimed at standardizing reproducibility assessments of CBMs and GEMs. The FROG framework encompasses four key analyses--Flux variability, Reaction deletion, Objective function, and Gene deletion--to produce standardized, numerically reproducible FROG reports. These reports serve as reference datasets, enabling model evaluators, curators, and independent researchers to verify the reproducibility of GEMs systematically. BioModels, a leading repository of systems biology models, has integrated FROG analysis into its curation workflow, enhancing the reproducibility and reusability of submitted GEMs. In our study evaluating 65 GEM submissions from the community, approximately 40% reproduced without intervention, 28% requiring minor adjustments, and 32% needing input from authors. The standardization introduced by FROG analysis facilitated the detection and resolution of issues, ultimately leading to the successful reproduction of all models. By establishing a standardized and comprehensive approach to evaluating GEM reproducibility, FROG analysis significantly contributes to making CBMs and GEMs more transparent, reusable, and reliable for the broader scientific community.

systems biology↗

bioRxiv2022

Metagenome-based metabolic modelling predicts unique microbial interactions in deep-sea hydrothermal plume microbiomes

Deep-sea hydrothermal vents are abundant on the ocean floor and play important roles in ocean biogeochemistry. In vent ecosystems such as hydrothermal plumes, microorganisms rely on reduced chemicals and gases in hydrothermal fluids to fuel primary production and form diverse and complex microbial communities. However, microbial interactions that drive these complex microbiomes remain poorly understood. Here, we use microbiomes from the Guaymas Basin hydrothermal system in the Pacific Ocean to shed more light on the key species in these communities and their interactions. We built metabolic models from metagenomically assembled genomes (MAGs) and infer possible metabolic exchanges and horizontal gene transfer (HGT) events within the community. We highlight possible archaea-archaea and archaea-bacteria interactions and their contributions to robustness of the community. Cellobiose, D-Mannose 1-phosphate, O2, CO2, and H2S were among the most exchanged metabolites. Ten microbes, including eight bacteria and two archaea, were identified as key contributors. These microorganisms uniquely enhanced the metabolic capabilities of the community by donating metabolites that cannot be produced by any other community member. Archaea from the DPANN group stood out as key microbes, benefiting significantly from accepting metabolites from other members of the microbiome. Amino acids were the key auxotrophy driving metabolic interactions in the community. Finally, over 200 horizontal gene transfer events were predicted in the community, the majority of which were between Gammaproteobacteria and Alphaproteobacteria. Overall, our study provides key insights into the microbial interactions that drive community structure and organisation in complex hydrothermal plumes and deep-sea microbiomes.

microbiology↗