Biology subjects

Seal, A.

Publications and source records attributed to Seal, A..

4 recordsLinked to original sources

bioRxiv2026

Transition of a Yeast Endosymbiont from a Free-living to Host-reliant Lifestyle Through Gene Loss and Horizontal Gene Transfer

Endosymbiosis is widespread throughout the tree of life. Understanding how the transition of a bacterial endosymbiont from facultative to host-dependent obligate life occurs is an important question for defining the origin of endosymbiosis. A novel gram-positive bacillus, Brevibacillus sp. TJ4 was isolated from the nitrogen-fixing yeast Rhodotorula mucilaginosa JGTA-S1, which houses several endobacteria within its cells. TJ4 can survive independently of yeast but exhibits genomic and metabolic features characteristic of an evolving endosymbiont, slowly assuming a host-dependent, obligate lifestyle. The TJ4 genome contains several incomplete pathways for carbohydrate, amino acid, vitamin, and cofactor metabolism, which is reflected in its increased reliance on host-derived nutrients and auxotrophy compared with that of other Brevibacillus spp. Comparative genomics revealed widespread genome rearrangements, loss of synteny, and multiple cross-genus and inter-kingdom horizontal gene transfer (HGT) events in TJ4 compared to other Brevibacillus spp. These HGTs include the acquisition of genes from bacteriophages and co-resident endobacteria of JGTA-S1. One such horizontally acquired gene, Type II 3-dehydroquinate dehydratase (AroQ), appears to have originated from the Rhodotorula host itself. This acquisition functionally restores the shikimate pathway in strain TJ4, as evidenced by the phylogenetic placement of AroQ from TJ4 within the clade of fungal AroQ homologs. Potential exploitation of the host JGTA-S1 appears to be a probable mode of endosymbiosis of TJ4, an evolving endosymbiont that we named Brevibacillus rhodotorulae sp. nov.

microbiology↗

bioRxiv2025

AOP Net: An AI-Enhanced Software Platform for the Visualization and Analysis of Complex Toxicological Pathways

AO_SCPLOWBSTRACTC_SCPLOWThe Adverse Outcome Pathway (AOP) framework is a cornerstone of 21st-century toxicology, providing a structured method for organizing mechanistic knowledge to support risk assessment. However, the inherent complexity of biological systems, characterized by interconnected signaling networks, reveals the limitations of simple, linear AOP representations. This has created a pressing need for advanced computational tools that can visualize and analyze these intricate AOP networks. This study introduces the AOP Network Viewer, a novel software platform designed to address the critical challenges of scalability, interactivity, and deep analysis in toxicological research. The system is built on a scalable client-server architecture with a graph database backend, supporting sophisticated interactive features such as multi-pathway selection, dynamic path-finding, and advanced filtering. The principal innovation of the AOP Network Viewer is its integrated AI Analysis Panel, a Large Language Model (LLM)-powered engine that provides a deep, context-aware analysis of selected network components. This AI system utilizes a unique three-layer prompt architecture to deliver domain-specific insights across seven specialized analytical modes. Case studies demonstrate the platforms utility in developing alternative testing strategies for endocrine disruptors, interpreting high-throughput screening data, and generating hypotheses for toxicity assessment of mixtures. The AOP Network Viewer is engineered to translate complex user queries into focused, interpretable biological networks, transforming AOP network visualization from a passive viewing experience into an interactive and intelligent analytical process, thereby accelerating mechanistic discovery and enhancing evidence-based regulatory decision-making. The app is source code is available at https://github.com/abhik1368/aop-visualizer-clean.

bioinformatics↗

bioRxiv2021

Enthalpic and Entropic Contributions to Interleaflet Coupling Drive Domain Registration and Anti-registration in Biological Membrane

Biological membrane is a complex self-assembly of lipids, sterols and proteins organized as a fluid bilayer of two closely stacked lipid leaflets. Differential molecular interactions among its diverse constituents give rise to heterogeneities in the membrane lateral organization. Under certain conditions, heterogeneities in the two leaflets can be spatially synchronised and exist as registered domains across the bilayer. Several contrasting theories behind mechanisms that induce registration of nanoscale domains have been suggested[1-3]. Following a recent study[4] showing the effect of position of lipid tail unsaturation on domain registration behavior, we decided to develop an analytical theory to elucidate the driving forces that create and maintain domain registry across leaflets. Towards this, we formulated a Hamiltonian for a stacked lattice system where site variables capture the lipid molecular properties such as the position of unsaturation and various other interactions that could drive phase separation and interleaflet coupling. We solve the Hamiltonian using Monte Carlo simulations and create a complete phase diagram that reports the presence or absence of registered domains as a function of various Hamiltonian parameters. We find that the interleaflet coupling should be described as a competing enthalpic contribution due to interaction of lipid tail termini, primarily due to saturated-saturated interactions, and an interleaflet entropic contribution from overlap of unsaturated tail termini. A higher position of unsaturation is seen to provide weaker interleaflet coupling. Thermodynamically stable nanodomains could also be observed for certain points in the parameter space in our bilayer model, which were further verified by carrying out extended Monte Carlo simulations. These persistent non-coalescing registered nanodomains close to the lower end of the accepted nanodomain size range also point towards a possible "nanoscale" emulsion description of lateral heterogeneities in biological membrane leaflets.

biophysics↗

bioRxiv2020

Structural and dynamical heterogeneity of water trapped inside Na+-pumping KR2 rhodopsin in the dark state

Photoisomerisation in retinal leads to a channel opening in the rhodopsins that triggers translocation or pumping of an ion/proton. Crystal structures of rhodopsins contain several structurally conserved water molecules. It has been suggested that water plays an active role in facilitating the ion pumping/translocation process by acting as a lubricant in these systems. In this work, we systematically investigate the localisation, structure, dynamics and energetics of the water molecules along the channel for the resting/dark state of KR2 rhodopsin. Employing several microseconds long atomistic molecular dynamics (MD) simulation of this trans-membrane protein system, we demonstrate the presence of five distinct water containing pockets/cavities separated by gateways controlled by the protein side-chains. There exists a strong hydrogen bonded network involving these buried water molecules and functionally important key residues. We present evidence of significant structural and dynamical heterogeneity in the water molecules present in these cavities with very rare exchange between them. The exchange time-scale of these buried water with bulk has an extremely wide range from tens of nanoseconds to > 1.5s! The translational and rotational dynamics of buried water are found to be strongly dependent on the protein cavity size and local interactions with classic signature of trapped diffusion and rotational anisotropy.

biophysics↗