Biology subjects

Bhattacharjee, B.

Publications and source records attributed to Bhattacharjee, B..

6 recordsLinked to original sources

bioRxiv2026

Persistently activated virus-specific CD8 T cells indicate antigen-driven immune aberrations in long COVID

Long COVID (LC) affects millions of people worldwide, yet its driving mechanisms remain incompletely defined and no treatment has been approved. Persistence of SARS-CoV-2 and reactivation of herpesviruses have been implicated in LC, but direct detection of these viral antigens in blood and tissues has been challenging. T cells are exquisitely sensitive to viral antigens, survey organs throughout the body, and can be readily sampled in peripheral blood. Using high-dimensional spectral flow cytometry and single-cell sequencing approaches with multiplexed peptide/HLA tetramers, we profiled virus-specific T cells from hundreds of people with LC and recovered controls. We identified a subset of people with LC that maintained elevated activation of CD8 T cells targeting SARS-CoV-2 spike and/or lytic antigens from Epstein-Barr virus, but not other viral specificities. Spike-specific cells in LC expressed genes linked to TCR stimulation, terminal effector differentiation, and exhaustion and demonstrated reduced functionality upon cognate peptide stimulation ex vivo. Thus, T cells from a subset of people with LC are likely chronically stimulated by persistent SARS-CoV-2 antigens. These findings establish the use of T cells as biosensors of persisting antigen in LC and other disease settings and may help develop new therapeutic strategies for LC.

immunology↗

bioRxiv2026

Transcriptomic Illuminations: How light intensity reshapes the Chlamydomonas reinhardtii cell cycle

The unicellular algae cell cycle can be divided into several phases, including the commitment point (CP), a point-of-no-return where the cell decides to divide, presumably based on reaching a critical cell size. Light plays a crucial role in the fitness of photosynthetic algal cells, affecting both CP timing and the number of daughter cells produced. So far, only few genes involved in CP have been described, and the presumed sizer and its signal(s) remain unidentified. Using synchronized cells and varying light intensities as a proxy, we explored the effects of light intensity in Chlamydomonas reinhardtii and observed both physiological and transcriptional changes occurring before and after CP under low light (LL) (100 {micro}mol m-{superscript 2} s-{superscript 1}) and optimal light (OL) (500 {micro}mol m-{superscript 2} s-{superscript 1}) conditions. Although CP was delayed by approximately 6 hours in LL, resulting in smaller mother cells and fewer daughter cells, the cells divided at the same time in both conditions. Overall, nucleic acid, protein, and energy reserve levels were lower in LL, with almost no starch produced. RNA-seq analysis identified several core genes shared between both conditions, with 201 genes expressed only in pre-CP1, 161 genes specific to post-CP1, and 582 shared across different phases. In LL, RNA-seq analysis showed an increase in differentially expressed genes (DEGs) in pre-CP1 compared to post-CP1, with an emphasis on photosynthesis, RNA metabolism, and organelle production before commitment, and cell division-related pathways (microtubules, DNA recombination) after CP1. In OL, the number of DEGs increased in post-CP1 by approximately 41% compared to pre-CP1, with a strong emphasis on protein production throughout the cell cycle.

cell biology↗

bioRxiv2026

Coordinated cell and chloroplast growth and its perturbation by chloroplast DNA replication inhibition in green algae

Coordination among cell growth, chloroplast expansion, and organelle genome dynamics is fundamental to algal physiology, yet its regulation remains unclear. We used time-resolved single-cell analyses to examine scaling relationships among cell size, chloroplast volume, nuclear dynamics, and nucleoid organization in Desmodesmus communis and Chlamydomonas reinhardtii under normal conditions and after inhibition of chloroplast DNA replication with nalidixic acid (NAL). Under control conditions, both species showed coordinated scaling among cell, chloroplast, and nuclear size, while nucleoid dynamics were driven mainly by changes in number. NAL disrupted these relationships in a species- and time-dependent manner. In C. reinhardtii, prolonged treatment uncoupled chloroplast and nuclear growth from cell expansion and led to fewer, enlarged nucleoids, consistent with impaired replication. In contrast, D. communis largely maintained coordinated scaling, with effects mainly limited to reduced nucleoid proliferation and delayed division. Temporal analyses indicated that NAL primarily affected nucleoid replication and segregation, with secondary consequences for chloroplast growth and cell-cycle progression. These findings identify chloroplast genome dynamics as a regulatory link between organelle growth and cell division.

cell biology↗

bioRxiv2026

From Light to Acetate: How Trophic Conditions Shape Growth and Cell Cycle Progression in Chlamydomonas reinhardtii

The unicellular green alga Chlamydomonas reinhardtii provides a tractable model for investigating how carbon availability influences metabolic organization and cell-cycle control in photosynthetic eukaryotes. Its capacity for autotrophic (light, CO), mixotrophic (light, CO, acetate), and heterotrophic (acetate, dark) growth enables systematic analysis of trophic-state-dependent regulation. We performed comparative transcriptomic analyses of strain 21gr grown under these three regimes at 30 {degrees}C. Mixotrophy resulted in the highest biomass accumulation and was associated with earlier cell-cycle commitment compared with autotrophy, whereas heterotrophy displayed delayed commitment and reduced growth. Transcriptomic profiling revealed coordinated upregulation of central carbon metabolic pathways under mixotrophy, including photorespiration, glycolysis, the oxidative pentose phosphate pathway, and tricarboxylic acid cycle functions, consistent with enhanced carbon flux and biosynthetic capacity. In contrast, heterotrophy preferentially induced acetate assimilation and glyoxylate cycle genes and was accompanied by elevated expression of cell-cycle regulators, including the CDK-inhibitory kinase WEE1. Together, these findings indicate that trophic mode modulates the coupling between carbon metabolism and cell-cycle progression, with mixotrophy supporting integrated metabolic and proliferative activity, whereas heterotrophy is associated with delayed cell-cycle timing and transcriptional signatures of metabolic adjustment.

plant biology↗

bioRxiv2025

Shape-Shifting Conotoxins Reveal Divergent Pore-Targeting Mechanisms in Nicotinic Receptors

The neuronal 7 nicotinic acetylcholine receptor (7-nAChR) and muscle-type nicotinic acetylcholine receptor (mt-nAChR) are pivotal in synaptic signaling within the brain and the neuromuscular junction respectively. Additionally, they are both targets of a wide range of drugs and toxins. Here, we utilize cryoEM to delineate structures of these nAChRs in complex with the conotoxins ImI and ImII from Conus imperialis. Despite nominal sequence divergence, ImI and ImII exhibit discrete binding preferences and adopt drastically different conformational states upon binding. ImI engages the orthosteric sites of the 7-nAChR, while ImII forms distinct pore-bound complexes with both the 7-nAChR and mt-nAChR. Strikingly, ImII adopts a compact globular conformation that binds as a monomer to the 7-nAChR pore and as an oblate dimer to the mt-nAChR pore. These structural characterizations advance our understanding of nAChR-ligand interactions as well as the subtle sequence variations that result in dramatically altered functional outcomes in small peptide toxins. Importantly, these results further elucidate the broad nature of cone snail toxin activities and highlight how targeted molecular evolution can give rise to functionally similar activities with surprisingly diverse mechanisms of action.

neuroscience↗

bioRxiv2020

Phylogenetic clustering of the Indian SARS-CoV-2 genomes reveals the presence of distinct clades of viral haplotypes among states

The first Indian cases of COVID-19 caused by SARS-Cov-2 were reported in February 29, 2020 with a history of travel from Wuhan, China and so far above 4500 deaths have been attributed to this pandemic. The objectives of this study were to characterize Indian SARS-CoV-2 genome-wide nucleotide variations, trace ancestries using phylogenetic networks and correlate state-wise distribution of viral haplotypes with differences in mortality rates. A total of 305 whole genome sequences from 19 Indian states were downloaded from GISAID. Sequences were aligned using the ancestral Wuhan-Hu genome sequence (NC_045512.2). A total of 633 variants resulting in 388 amino acid substitutions were identified. Allele frequency spectrum, and nucleotide diversity ({pi}) values revealed the presence of higher proportions of low frequency variants and negative Tajimas D values across ORFs indicated the presence of population expansion. Network analysis highlighted the presence of two major clusters of viral haplotypes, namely, clade G with the S:D614G, RdRp: P323L variants and a variant of clade L [Lv] having the RdRp:A97V variant. Clade G genomes were found to be evolving more rapidly into multiple sub-clusters including clade GH and GR and were also found in higher proportions in three states with highest mortality rates namely, Gujarat, Madhya Pradesh and West Bengal.

genomics↗