Biology subjects

Sandin, S.

Publications and source records attributed to Sandin, S..

5 recordsLinked to original sources

bioRxiv2026

Native in situ architecture of the human inactive X chromosome revealed by correlative light and electron microscopy

Knowledge of the nuclear organization of specific chromatin domains at the ultrastructural level remains limited. To address this, we employed correlative light and electron microscopy (CLEM) approaches to investigate the inactive X chromosome (Xi) in female human RPE1cells. Tandem fusion of macroH2A (mH2A), a histone variant enriched on the Xi, to eGFP and APEX2 enabled direct labeling and identification of the Xi by light microscopy, transmission electron microscopy, and electron tomography using conventional CLEM. The eGFP tag further allowed us to visualize the Xi at single nucleosome resolution under close-to-native conditions using cryo-CLEM. We found that, although heterochromatin domains of the Xi are substantially larger than those of autosomal regions, their chromatin density was not significantly different. Furthermore, our data reveal the organization of the interchromatin compartment (IC) within the Xi, characterized by a network of larger lacunae and smaller channels. Overall, we provide an ultrastructural characterization of a specific heterochromatin domain at unprecedented resolution, advancing our understanding of 3D chromatin organization and nuclear architecture in situ.

cell biology↗

bioRxiv2026

Self-Organized Pattern Formation of a Common Tropical Alga

Recent in-situ observations within a tropical coral reef have revealed novel polygonal patterns of the calcifying green alga Halimeda. The observed patterns showed no evidence of a matching exogenous template in structural reef morphology, distribution of biological competitors for space, or other environmental factors, suggesting the pattern is the result of endogenous, nonlinear pattern forming dynamics. A simplified, spatially explicit numerical model is proposed that simulates a feedback whereby Halimeda preferentially grows in regions less conducive to the growth of corals (when corals are the dominant spatial competitor), and coral growth is inhibited in regions of dense Halimeda. Model results reveal self-organized emergent polygons of Halimeda cover that qualitatively match observations.

ecology↗

bioRxiv2025

Central carbon metabolism switching in lytic versus temperate coral reef viral communities

Coral reefs are declining globally due in part to bacterial overgrowth, a process known as microbialization. However, the role of bacteriophages that may inhibit microbialization by infecting and killing these bacteria remains poorly understood, especially their metabolic impacts on bacterial proliferation. To address this, we analyzed central carbon metabolism gene frequencies in viral communities from healthy (lytic-dominated) and degraded (temperate-dominated) Central Pacific coral reefs. We found that viral metabolism shifted broadly from being dominated by metabolism that builds up pools of central intermediates on degraded reefs dominated by temperate viral infection ("anaplerotic" reactions) to metabolism that consumes these pools to prioritize production of metabolic precursors for virion construction on healthy reefs dominated by lytic infection ("cataplerotic" reactions). This switch was shown by the over-representation of Entner-Doudoroff (ED) glycolysis genes on degraded, temperate-dominated reefs and of pentose phosphate pathway (PPP) and reductive tricarboxylic acid cycle (TCA) genes on healthy, lytic-dominated reefs. As a result of this metabolic dichotomy, our qualitative compartment modeling revealed two distinct ecosystem states: (i) healthy reefs, where lytic viral metabolism enhances viral production and suppresses bacterial overgrowth, and (ii) degraded reefs, where temperate viral metabolism accelerates bacterial proliferation. Because viral switching between lytic and temperate lifestyles is a known function of host physiological state, these findings position viral metabolism as both a driver of reef decline and a conservation lever, with metabolically mediated "re-viralization" offering a novel strategy to restore reef resilience.

ecology↗

bioRxiv2025

Uromodulin velcro sheets and their interaction with uropathogenic E. coli

Homopolymeric uromodulin (UMOD), the most abundant protein in human urine, protects against urinary tract infections (UTI) by acting as a decoy for uropathogenic E. coli (UPEC). Using cryo-electron tomography (ET), we show that urinary UMOD filaments naturally form sheets that interact with UPEC type I pili. Sheet formation is salt-dependent, and we resolve their high-resolution structure using single-particle cryo-electron microscopy (EM). This reveals a lateral interface between polymers, whose mutation disrupts UMOD filament bundle formation in mammalian cells. Branchless egg coat protein ZPD also forms sheets, and cryo-ET of elastase-treated UMOD indicates that absence of N-terminal branches promotes the stacking of UMOD-like protein sheets into thick 3D matrices. These results rationalize early observations of salt-dependent aggregation of UMOD, explain how UMOD can assemble into extended velcro-like structures that efficiently inactivate a multitude of adhesive UPEC pili, and suggest how UMOD-like molecules can generally organize into supramolecular structures of variable thickness.

biophysics↗

bioRxiv2019

Quantitative proximity proteomics resolves the epithelial apical-lateral border and uncovers a vertebrate marginal zone defined by the polarity protein Pals1

Epithelial apico-basal polarity is established through the asymmetric cortical distribution of the Par, Crumbs and Scribble polarity modules. Apical (Par and Crumbs) and basolateral (Scribble) polarity modules overlap at the apical-lateral border, which, in mammals, is defined by the apical junctional complex (AJC). The AJC is composed of tight junctions (TJ) and adherens junctions (AJ) and plays fundamental roles in epithelial morphogenesis and plasticity. However, the molecular composition and precise sub-junctional organization of the AJC and its associated polarity regulators are still not well defined. Here we used the peroxidase APEX2 for quantitative proximity proteomics (QPP) and electron microscopy (EM) imaging to generate a nanometer-scale spatio-molecular map of the apical-lateral border in fully polarized MDCK-II cells. Using Par3 and Pals1 as surrogates for QPP we present a spatially resolved network of [~]800 junction-associated proteins. The network dissects TJ and AJ components and provides strong evidence that TJ are composed of distinct apical and basal subdomains. Moreover, we find that Pals1 and its binding partners PatJ, Lin7c and Crumbs3 define a hitherto unidentified membrane compartment apical of TJ, which we coin the vertebrate marginal zone (VMZ). The VMZ is physically associated with HOMER scaffolding proteins, regulators of apical exocytosis, and membrane-proximal HIPPO pathway proteins. Taken together our work defines the spatial and molecular organization of the apical-lateral border in fully polarized mammalian epithelial cells, reveals an intriguing molecular and spatial conservation of invertebrate and vertebrate cell polarity protein domains, and provides a comprehensive resource of potentially novel regulators of cell polarity and the mammalian AJC.

cell biology↗