Biology subjects

Santhosh, S.

Publications and source records attributed to Santhosh, S..

10 recordsLinked to original sources

bioRxiv2026

Achiral Odd Mechanics in Cell Monolayers

Cell monolayers are active, orientationally ordered materials whose mechanics can depart from near-equilibrium behavior. Existing continuum theories often inherit assumptions from equilibrium liquid-crystal physics, motivating explicit nonequilibrium formulations. Here, we develop a minimal continuum model of two-dimensional monolayers based on odd mechanics, accounting for broken symmetries and nonequilibrium dynamics. We show that nematic order can support an odd viscous modulus generated by broken time-reversal symmetry and spatial anisotropy, without chirality. The model reproduces half-integer defect motion and stress profiles in Madin-Darby canine kidney (MDCK) monolayers, as well as defect-associated cell accumulation and depletion in neural progenitor and ovarian mesothelium systems. Finally, we estimate the viscous-moduli tensor from measured stress, velocity, and orientation fields in MDCK monolayers and identify a nonzero odd modulus. Our results show that odd mechanics provides a minimal framework for nonequilibrium cell monolayers, complementing conventional active-nematic theories.

cell biology↗

bioRxiv2025

Tissue geometry and mechanochemical feedback initiate rotational migration in Drosophila

Collective migration of epithelial cells drives diverse tissue remodeling processes. In many cases, a free tissue edge polarizes the cells to promote directed motion, but how edge-free or closed epithelia initiate migration remains unclear. Here, we show that the rotational migration of follicular epithelial cells in the Drosophila egg chamber is a self-organizing process. Combining experiments and theoretical modeling, we identify a positive feedback loop in which the mechanosensitive behavior of the atypical cadherin Fat2 synergizes with the rigid-body dynamics of the egg chamber to both initiate and sustain rotation. Mechanical constraints arising from cell-cell interactions and tissue geometry further align this motion around the egg chambers anterior-posterior axis. Our findings reveal a biophysical mechanism -- combining Fat2-mediated velocity-polarity alignment, rigid-body dynamics, and tissue geometry -- by which a closed epithelial tissue self-organizes into persistent, large-scale rotational migration in vivo, expanding current flocking theories.

cell biology↗

bioRxiv2025

Coherent Structures in Active Flows on Dynamic Surfaces

Coherent structures--flow features that organize material transport and deformation--are central to analyzing complex flows in fluids, plasmas, and active matter. Yet, identifying such structures on dynamic surfaces remains an open challenge, limiting their application to many living and synthetic systems. Here, we introduce a geometric framework to extract Lagrangian and Eulerian coherent structures from velocity data on arbitrarily shaped, time-evolving surfaces. Our method operates directly on triangulated meshes, avoiding global parametrizations while preserving objectivity and robustness to noise. Applying this framework to active nematic vesicles, collectively migrating epithelial spheroids, and beating zebrafish hearts, we uncover hidden transport barriers and Lagrangian deformation patterns--such as dynamic attractors, repellers, isotropic and anisotropic strain--missed by conventional Eulerian analyses. This approach offers a new perspective on soft and living matter, revealing how geometry and activity can be harnessed to program synthetic materials, and how Lagrangian strain and principal deformation directions can help uncover mechanosensitive processes and directional cues in morphogenesis.

biophysics↗

bioRxiv2024

Unveiling the guardians: IL-26-expressing MAIT cells protect epithelial barrier function and are dysregulated in Crohn's disease

BACKGROUND & AIMSInflammatory bowel disease (IBD) is characterized by a dysregulated immune response against the hosts microbiome. Mucosal-associated invariant T (MAIT) cells recognize microbiota-derived riboflavin metabolites and play a crucial role in mucosal homeostasis. However, their specific role in IBD remains enigmatic. MAIT cells express IL-26, a novel IL-10 family cytokine with a controversial role in IBD. We investigated the functions of MAIT cells and IL-26 in IBD using a unique combination of state-of-the-art 3D human intestinal tissue models and clinical samples. METHODSWe analyzed MAIT cells from the peripheral blood and intestinal tissue of Crohns disease (CD) patients, using immunofluorescence staining and flow cytometry to describe the phenotype and IL-26 expression of MAIT cells. We used 3D iPSC-derived intestinal organoids as a complex in vitro model of human tissue and RNA sequencing and functional assays such as wound healing assay to study the role of IL-26 in mucosal homeostasis and inflammation. RESULTSWe observed a reduction of MAIT cells in the peripheral blood of CD patients compared to healthy donors (1.5 {+/-} 0.4%; 4.1 {+/-} 1.1%; p < .0065) and a significant decrease of MAIT cells in inflamed compared to non-inflamed ileum of CD patients (0.1 {+/-} 0.03%; 0.17 {+/-} 0.05%; p < .042). MAIT cells were found pathologically activated in inflamed tissue, exhibiting differences in CD8 and CD4 expression and dysregulation of IL-26 expression. Furthermore, we demonstrated a protective role of IL-26 in mucosal homeostasis and inflammation in the iPSC-derived organoid model. CONCLUSIONOur results show a crucial role for IL-26 and MAIT cells in the homeostasis of intestinal tissue and in the pathogenesis of IBD. These cells may therefore represent new therapeutic targets for CD patients.

immunology↗

bioRxiv2023

Sperm competition favours intermediate sperm size in a hermaphrodite

Sperm competition is a potent mechanism of post-copulatory sexual selection that has been found to shape reproductive morphologies and behaviours in promiscuous animals. Especially sperm size has been argued to evolve in response to sperm competition through its effect on sperm longevity, sperm motility, the ability to displace competing sperm and ultimately fertilization success. Additionally, sperm size has been observed to co-evolve with female reproductive morphology. Theoretical work predicts that sperm competition may select for longer sperm but may also favour shorter sperm if sperm size trades off with number. In this study, we studied the relationship between sperm size and post-mating success in the free-living flatworm, Macrostomum lignano. Specifically, we used inbred isolines of M. lignano that varied in sperm size to investigate how sperm size translated into the ability of worms to transfer and deposit sperm in a mating partner. Our results revealed a hump-shaped relationship with individuals producing sperm of intermediate size having highest sperm competitiveness. This finding broadens our understanding of the evolution of sperm morphology by providing empirical support for stabilizing selection on sperm size under sperm competition.

evolutionary biology↗

bioRxiv2023

IL-1R signaling drives enteric glia-macrophage interaction in colorectal cancer progression

Enteric glial cells (EGCs) have been implicated in colorectal cancer (CRC) pathogenesis. However, their precise mechanisms of interaction with the CRC immune cell compartment and pro-tumorigenic role remain unclear. This study aimed to investigate the immunomodulatory effects of EGCs on tumor-associated macrophages (TAMs) and their involvement in CRC progression. Using EGC depletion and supplementation models, we assessed the impact of EGCs on the immunomodulation of orthotopic murine CRC. Furthermore, by making use of Bulk RNA-sequencing of CRC EGCs and single-cell sequencing of the tumor microenvironment, we identified the factors involved in the EGC-TAM crosstalk. Findings demonstrate that EGCs acquire a reactive and immunomodulatory phenotype in both murine CRC models and patients, influencing TAM differentiation. Mechanistically, secretion of IL-1 by tumor-infiltrating monocytes and macrophages triggers the phenotypic and functional switch of CRC EGCs via IL-1R. Consequently, tumor EGCs secrete IL-6, promoting the differentiation of monocytes into pro-tumorigenic SPP1+ TAMs. Importantly, the reactive tumor EGCs phenotype correlates with worse disease outcomes in preclinical models and CRC patients. Here we uncover a previously unexplored neuroimmune interaction between EGCs and TAMs within the colorectal tumor microenvironment, informing potential therapeutic strategies and enhancing our understanding of CRC progression. eTOC SummaryOur study unveils a novel neuroimmune interaction between enteric glia and TAMs in colon carcinoma. Monocyte/Macrophage-derived IL-1 activates enteric glia, leading to the differentiation of pro-tumorigenic SPP1+ TAMs via glial-derived IL-6. Blocking glial IL-1R-signaling reduces colonic tumor lesions, highlighting IL-1R as a potential therapeutic target.

cancer biology↗

bioRxiv2023

Intercellular interaction between FAP fibroblasts and CD150 inflammatory monocytes mediates fibro-stenosis in Crohn's disease

Crohns disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibro-stenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate complex intercellular interactions leading to fibro-stenosis in CD, we analysed the transcriptome of cells isolated from the transmural ileum of CD patients, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from non-CD patients. Our computational analysis revealed that pro-fibrotic signals from a subset of monocyte-derived cells expressing CD150 induce a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) production. Therapeutic inhibition of TWIST1 inhibits fibroblast activation, reducing ECM production and deposition. These findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibro-stenosis in CD.

immunology↗

bioRxiv2023

Zebrahub - Multimodal Zebrafish Developmental Atlas Reveals the State Transition Dynamics of Late Vertebrate Pluripotent Axial Progenitors

Elucidating the developmental processes of organisms requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by trajectory reconstructions. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enabling in silico fate mapping experiments. To demonstrate the versatility of our multi-modal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of Neuro-Mesodermal Progenitors (NMPs). Our publicly accessible web-based platform, Zebrahub, is a foundational resource for studying developmental processes at both transcriptional and spatiotemporal levels, providing researchers with an integrated approach to exploring and analyzing the complexities of cellular lineages during zebrafish embryogenesis.

developmental biology↗

bioRxiv2019

Adult crowding induces sexual dimorphism in chronic stress-response in Drosophila melanogaster

Stress-induced mood disorders such as depression and anxiety are sexually dimorphic in human beings. Studying behavioural stress-responses in non-human animal models can help better understand the behavioural manifestations of these disorders and the dimorphism in their prevalence. Here we explore how sexes show differential behavioural responses to different chronic stressors, both abiotic and biotic, by using outbred populations of Drosophila melanogaster. The behaviours studied - namely, anhedonia, motivation to explore a novel habitat, locomotor activity and sleep levels - have been well-investigated in human and rodent-based models of stress disorders. These behaviours were studied in the context of two different stressors - mechanical perturbation and adult crowding. Responses to stress were found to be sexually dimorphic, and stressed females showed more behavioural changes, such as a reduced motivation to explore a novel habitat. Furthermore, adult crowding caused a greater number of sexually dimorphic behavioural changes than mechanical perturbation. For instance, while mechanical perturbation caused anhedonia across sexes, only females were anhedonic after crowding. We thus make a case for Drosophila melanogaster as a model system for studying sexual dimorphism in stress-induced mood disorders in humans.\n\nSUMMARY STATEMENTFemale fruit flies, like their human counterparts, are more prone to chronic stress-induced mood disorders like anhedonia or reduced activity. This sexual dimorphism was more evident in a biotic stress.

ecology↗

bioRxiv2019

Whole genome sequencing and comparative genomic analysis reveal novel allelic variations unique to a purple colored rice landrace (Oryza sativa ssp. indica cv. Purpleputtu)

Purpleputtu (Oryza sativa ssp. indica cv. Purpleputtu) is a unique rice landrace from southern India that exhibits predominantly purple color. This study reports the underlying genetic complexity of the trait and associated domestication and de-domestication processes during its coevolution with present day cultivars. Along-with genome level allelic variations in the entire gene repertoire associated with purple, red coloration of grain and other plant parts. Comparative genomic analysis of the whole genome sequence of Purpleputtu (PP) revels total of 3,200,951 variants including 67,774 unique variations were observed in PP when compared with 108 rice genomes. Multiple sequence alignment uncovered a 14bp deletion in Rc (Red colored, a transcription factor of bHLH class) locus of PP, a key regulatory gene of anthocyanin biosynthetic pathway. Interestingly, this deletion in Rc gene is a characteristic feature of the present-day white pericarped rice cultivars. Phylogenetic analysis of Rc locus revealed a distinct clade showing proximity to the progenitor species rufipogon and nivara. In addition, PP genome exhibits a well conserved a 4.5Mbp region on chromosome 5 that harbors several loci associated with domestication of rice. Further, PP showed 1,387 unique SNPs compared to 3,024 lines of rice (SNP-Seek database). The results indicate that PP genome is rich in allelic diversity and can serve as an excellent resource for rice breeding for a variety of agronomically important traits such as disease resistance, enhanced nutritional values, stress tolerance and protection from harmful UV-B rays.

genomics↗