Biology subjects

Panigrahi, S.

Publications and source records attributed to Panigrahi, S..

8 recordsLinked to original sources

bioRxiv2025

Dynamics and interplay of gene expression and chromosome organization across a predatory lifecycle

The obligate predatory bacterium Bdellovibrio bacteriovorus alternates between a motile attack phase and a growth phase inside another bacterium, during which it undergoes multiple rounds of DNA replication followed by non-binary division and progeny release. How its chromosome is dynamically reorganized across these contrasting states remains unclear. Here, we used synchronized predatory infections combined with time-resolved RNA-seq, Hi-C, ChIP-seq, and quantitative microscopy to map transcriptional activity and chromosome architecture across seven key stages of the predatory lifecycle. We uncover a dramatic shift in nucleoid organization - from an ultra-compact, transcriptionally restricted state in attack-phase cells to a progressively decompacted, ori-centered conformation during intracellular replication. Notably, distinct transcriptional and chromosome folding states not only mark the canonical attack and growth phases, but also critical transitions such as prey invasion, replication onset, and predator division. Temporal gene expression profiles reflect the coordinated regulation of core cellular functions across the predatory cycle. Furthermore, spatial localization of RNA polymerase, ribosomes, DNA-binding proteins, and freely diffusing proteins highlight the tight, cell cycle-dependent coupling between nucleoid compaction, chromosome accessibility, and transcriptional activity. Altogether, our findings reveal the intricate dynamics and coordination of genome folding and gene expression in a complex bacterial cell cycle driven by prey-predator interactions.

microbiology↗

bioRxiv2024

HieVi: Protein Large Language Model for proteome-based phage clustering

Viral taxonomy is a challenging task due to the propensity of viruses for recombination. Recent updates from the ICTV and advancements in proteome-based clustering tools highlight the need for a unified framework to organize bacteriophages (phages) across multiscale taxonomic ranks, extending beyond genome-based clustering. Meanwhile, self-supervised large language models, trained on amino acid sequences, have proven effective in capturing the structural, functional, and evolutionary properties of proteins. Building on these advancements, we introduce HieVi, which uses embeddings from a protein language model to define a vector representation of phages and generate a hierarchical tree of phages. Using the INPHARED dataset of 24,362 complete and annotated viral genomes, we show that in HieVi, a multi-scale taxonomic ranking emerges that aligns well with current ICTV taxonomy. We propose that this method, unique in its integration of protein language models for viral taxonomy, can encode phylogenetic relationships, at least up to the family level. It therefore offers a valuable tool for biologists to discover and define new phage families while unraveling novel evolutionary connections.

genomics↗

bioRxiv2024

Temporal dynamics of inflammatory and transcriptome changes in the myocardium in a murine model of cardiac arrest

BackgroundIt is increasingly recognized that inflammatory changes play a significant role in myocardial injury following cardiac arrest. However, the pathophysiological mechanisms responsible for functional changes in the myocardium following the event remain incompletely understood. Here, we characterize the transcriptomic and immunological changes in a mouse model of cardiac arrest to explore the roles of epinephrine and ischemia/reperfusion on myocardial inflammation. Methods and ResultsMale and female mice (C57BL/6J) were divided into three groups: (1) Naive (anesthesia only), (2) Sham (anesthesia + saline injection + epinephrine), and (3) Arrest (8-minute cardiac arrest followed by resuscitation (anesthesia + potassium chloride + epinephrine). We monitored the animals over 0.5, 1, 3, and 7 days with serial echocardiography. Hearts were harvested for transcriptomic analysis and inflammatory changes as assessed by flow cytometry and immunohistochemistry. Plasma samples were collected for cytokine signaling analysis by multiplex ELISA. Our data indicate that the cardiac arrest group have increased infiltrating neutrophils in the myocardium and elevated plasma levels of pro-inflammatory cytokines, peaking at 0.5 days after the initial insult and subsequently resolving. In contrast, Sham mice displayed less pronounced inflammatory changes, which peaked at 1 day after the procedure. Notably, these inflammatory alterations coincided with cardiac stunning, as demonstrated by echocardiography. ConclusionsIn our murine model of cardiac arrest, epinephrine exposure and ischemia/reperfusion induce significant inflammatory changes in the myocardium with increased infiltrating neutrophils and elevated circulating cytokines which subsequently resolve in a time-dependent manner. These changes correlate with improving cardiac function by echocardiography.

immunology↗

bioRxiv2024

Antibiotic-Induced Morphological Changes Enhance Phage Predation: A Mathematical Model of Plaque Formation in Structured Environments

A distinctive manifestation of phage infection in solid media is the appearance of lysis plaques, which correspond to the circular thinning of a bacterial lawn. During plaque formation, successive cycles of phage replication generally take place from a single point of infection and spread radially in a matrix of immobilized bacterial hosts. Many different factors affect plaque size, such as the composition and the reticulation of the propagation matrix, the characteristics of the phage, but also parameters related to the physiology of the bacterial host. Since combined administration of both antibiotics and phages is a common practice during compassionate treatments, our research focuses on the effects of antibiotics on phage predation, which can be of crucial importance for the therapeutic applications of phages. It has been previously observed that the presence of antibiotics at sublethal concentrations can affect drastically bacterial physiology, allowing phages to spread more rapidly and resulting in better bacterial eradication. Previous experimental work has focused on the phage characteristics that influence plaque size. However, as plaque formation is strongly influenced by host growth dynamics, a comprehensive model integrating both the host growth and phage infection parameters is required. In this work, we suggest that plaque enlargement is linked to morphological changes of the host that have an impact on the rate of epidemic propagation and certainly on phage diffusion into the matrix. To support this hypothesis, we characterized the growth parameters of two different phages and bacteria in semi-solid media in the presence of various antibiotics. By combining these data, we have produced a mathematical model that accounts for these observations and explains the increase in plaque size when the host morphology is affected. Significance StatementThis study provides new insights into the phenomenon of Phage-Antibiotic Synergy (PAS) by demonstrating that antibiotic-induced morphological changes in bacterial hosts play a critical role in enhancing phage propagation in structured environments. By linking these morphological alterations--such as cell filamentation and bloating--to increased lysis plaque size, the research underscores the importance of host dynamics in phage therapy. The development of a mathematical model integrating both host growth and phage infection parameters offers a novel framework for understanding and optimizing phage-based treatments in the presence of antibiotics, potentially improving therapeutic outcomes.

microbiology↗

bioRxiv2022

Probing the Biology of Zinc Alpha2-Glycoprotein and the role it plays in cachexia

Cachexia is a metabolic disease that results in drastic weight loss and muscle wasting. 20% of total cancer patients will die due to cachexia related complications. ZAG contributes to the regulation of weight and body fat through lipid and glucose metabolism. In healthy individuals, ZAG exerts a homeostasis effect by inducing lipolysis of adipose tissue to help reduce fat storage and overall weight. ZAG is upregulated in various carcinomas and cancer patients with upregulated ZAG are observed to lose weight rapidly. The mutants of ZAG which are the 4 amino acids Tryptophan 148, Arginine 73, Phenylalanine 101, Isoleucine 76 have all been mutated to Alanine. The effect of mutants and the wild type ZAG can also be found out by conducting experiments. ZAG has a potential lipid binding site that could be imperative to the function of ZAG. A lipolysis colorimetric kit allows us to measure the ZAG variants effects on 3T3 adipose cells to determine what {beta}-adrenoreceptor signaling pathways are being utilized in its lipolytic effect. The Tryptophan-Alanine mutant showed increased lipolysis after 1h treatment than other variants. The time period is also a rate limiting step which can play major factor in lipolysis. The ultimate goal is to identify the ligand(s) and the interactions between them and ZAG. The design of a therapeutic would give patients options of treatments brought about by attenuating the weight loss. With this, it would offer a better prognosis for patients and provide them with a greater quality of life.

cancer biology↗

bioRxiv2021

Mapping QTLs for phenotypic and morpho-physiological traits related to grain yield under late sown conditions in wheat (Triticum aestivum L.)

The elevating temperature makes heat stress one of the major issues for wheat production globally. To elucidate genetic basis and map heat tolerance traits, a set of 166 doubled haploid lines (DHLs) derived from the cross between PBW3438/IC252874 was used. The population was evaluated under Normal sown (NS) and late sown (LS) conditions, by exposing to heat stress during rabi season. The canopy temperature (CT) showed positive correlations with grain yield, whereas Soil plant analysis development (SPAD) was not significantly correlated and associated with GY in both the normal and late sown conditions. Composite interval mapping (CIM) identified total 12 Quantitative trait loci (QTLs) viz., 2 (Normal sown), 10 (late sown) mapped on linkage groups 1A, 1D, 2B, 2D, 3B, 4D, 5B and 6D, during both the crop seasons 2017-18 and 2018-19. Combining the results of these QTLs revealed a major stable QTL for grain yield (GY) on chromosome 3B with 11.84% to 21.24% explaining phenotypic variance under both sowing conditions. QTL for CT and SPAD was detected on chromosome 1A while QTL for GY on chromosome 3B and 5B. The identified QTLs in the genomic regions could be targeted for genetic improvement and marker assisted selection for heat tolerance in wheat. The tools like SPAD and CT could be exploited to screen the large number of breeding lines.

plant biology↗

bioRxiv2020

Regulation of intracellular signaling and neuron function by Bardet-Biedl Syndrome proteins in patient-specific iPSC-derived neurons

Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder caused by mutations in genes encoding components of the primary cilium and characterized by hyperphagic obesity. We developed a cellular model of BBS using induced pluripotent stem cell (iPSCs)-derived hypothalamic arcuate-like neurons. BBS mutations BBS1M390R and BBS10C91fsX95 did not affect neuron differentiation efficiency but caused morphological defects including impaired neurite outgrowth and longer primary cilia. Expression of intact BBS10 normalized cilia length. Single-cell RNA sequencing (scRNA-seq) of BBS1M390R hypothalamic neurons identified several down regulated pathways including insulin and cAMP signaling, and axon guidance. In agreement with scRNA-seq data, insulin-induced AKT phosphorylation at Thr308 was reduced in BBS1M390R and BBS10c91fsX95 human fibroblasts and iPSC-derived neurons, as well as in BBS10 knockdown iPSC-derived neurons. Overexpression of intact BBS10 fully restored insulin receptor tyrosine phosphorylation in BBS10c91fsX95 neurons. Mutations in BBS1 and BBS10 impaired leptin-mediated p-STAT3 activation in both human primary fibroblasts and iPSC-derived hypothalamic neurons. Correction of the BBS mutation by CRISPR rescued leptin signaling. POMC expression in BBS1M390R and BBS10 C91fsX95 iPSC-derived hypothalamic neurons was downregulated, as was hypothalamic Pomc in BBS1M390R knockin (KI) mice. In the aggregate, these data provide insights into the anatomic and functional mechanisms by which components of the BBsome in CNS primary cilia mediate effects on energy homeostasis.

cell biology↗

bioRxiv2020

MiSiC, a general deep learning-based method for the high-throughput cell segmentation of complex bacterial communities

Studies of microbial communities by live imaging require new tools for the robust identification of bacterial cells in dense and often inter-species populations, sometimes over very large scales. Here, we developed MiSiC, a general deep-learning-based segmentation method that automatically segments a wide range of spatially structured bacterial communities with very little parameter adjustment, independent of the imaging modality. Using a bacterial predator-prey interaction model, we demonstrate that MiSiC enables the analysis of interspecies interactions, resolving processes at subcellular scales and discriminating between species in millimeter size datasets. The simple implementation of MiSiC and the relatively low need in computing power make its use broadly accessible to fields interested in bacterial interactions and cell biology.

microbiology↗