Biology subjects

Jain, S. S.

Publications and source records attributed to Jain, S. S..

4 recordsLinked to original sources

bioRxiv2025

Investigating the distribution of antibiotic resistance genes in relation to bacterial, fungal, and functional diversity in a hay field.

The spread of antibiotic resistance in pathogenic bacteria is one of the most pressing public health threats of the 21st century, with at least 5 million deaths currently associated with it. While recent work has shown the importance of environmental reservoirs in the emergence of antibiotic resistance genes (ARGs), it is unclear which features of microbial diversity relate to ARGs of clinical relevance. Here, we investigate the role of bacterial, fungal, and functional diversity on the distribution of clinical and environmental ARGs along a single transect located in an aging hay field on an otherwise active farm. This transect spans a length of several hundred meters, increasing in distance from an agricultural access road and stream. We use 16S rRNA and ITS amplicon sequencing to measure bacterial and fungal diversity respectively, in combination with whole-genome sequencing (WGS) to characterize functional and ARG diversity. We find increasing bacterial and functional diversity along the transect, as well as distinct community structures for both bacteria and fungi. While we find that the diversity of environmental ARGs is significantly correlated with both bacterial and fungal diversity, clinical ARG diversity only significantly decreased as fungal diversity increased. Our results suggest that while microbial diversity increases with distance from the road and stream; and this diversity tends to determine the diversity of the majority of ARGs; this trend is not observed for ARGs of clinical relevance, which appear to be largely driven by the variety of fungal groups in the environment.

ecology↗

bioRxiv2024

Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant

Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments released from dying cells into the circulation. We analyzed 130 blood samples collected from 44 patients at different time points after transplant. Sequence-based methylation of cfDNA fragments were mapped to patterns established to identify cell types in different organs. For liver cell types DNA methylation patterns and multi-omic data integration show distinct enrichment in open chromatin and regulatory regions functionally important for the respective cell types. We find that multi-tissue cellular damages post-transplant recover in patients without allograft injury during the first post-operative week. However, sustained elevation of hepatocyte and biliary epithelial cfDNA beyond the first week indicates early-onset allograft injury. Further, cfDNA composition differentiates amongst causes of allograft injury indicating the potential for non-invasive monitoring and timely intervention.

molecular biology↗

bioRxiv2024

Multi-SpinX: An Advanced Framework for Automated Tracking of Mitotic Spindles and Kinetochores in Multicellular Environments

SpinX, an AI-guided spindle tracking software, allows the 3-dimensional (3D) tracking of metaphase spindle movements in mammalian cells. Using over 900 images of dividing cells, we create the Multi-SpinX framework to significantly expand SpinXs applications: a) to track spindles and cell cortex in multicellular environments, b) to combine two object tracking (spindle with kinetochores marked by centromeric probes) and c) to extend spindle tracking beyond metaphase to prometaphase and anaphase stages where spindle morphology is different. We have used a human-in-the-loop approach to assess our optimisation steps, to manually identify challenges and to build a robust computational pipeline for segmenting kinetochore pairs and spindles. Spindles of both H1299 and RPE1 cells have been assessed and validated for use through Multi-SpinX, and we expect the tool to be versatile in enabling quantitative studies of mitotic subcellular dynamics.

cell biology↗

bioRxiv2020

Molecular basis for substrate recruitment to the PRMT5 methylosome

PRMT5 is an arginine methyltransferase and a therapeutic target in MTAP null cancers. PRMT5 utilizes adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (pICln/CLNS1A, RIOK1 and COPR5) and show it is necessary and sufficient for interaction with PRMT5. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosome assembly complexes. Genetic disruption of the PRMT5-substrate adaptor interface leads to a hypomorphic decrease in growth of MTAP null tumor cells and is thus a novel site for development of therapeutic inhibitors of PRMT5.

cancer biology↗