bioRxiv Science⌕ Search

Biology subjects

Schreiber, M.

Publications and source records attributed to Schreiber, M..

At least 19 recordsLinked to original sources

Rethinking Syndecan-1 as a Marker of Trauma-Induced Endothelial Injury

Syndecan-1 (SDC1), a transmembrane proteoglycan and component of the glycocalyx, is widely considered the key circulating biomarker of endothelial dysfunction in trauma and critical illness. However, the tissue distribution of SDC1 and the cellular origin of plasma SDC1 in health and disease are incompletely understood. This series of experiments integrates immunostaining, spatial transcriptomics (GeoMx Digital Spatial Profiler (DSP) and Xenium), and single-cell atlases to map SDC1, as well as the other three members of the syndecan family, syndecan-2 (SDC2), syndecan-3 (SDC3), and syndecan-4 (SDC4), across mouse and human tissues, including the lung, gastrointestinal tract, and brain. Across modalities, SDC1 primarily localizes to epithelial compartments, as demonstrated by colocalization with epithelial markers and enrichment in epithelial cell types in the lung and gut. Spatial profiling further identifies SDC1 and SDC4 enrichment in airway epithelial niches, SDC3 in endothelial-rich regions, and SDC2 distributed more broadly across compartments. Mouse and human single-cell atlases confirm epithelial predominance of SDC1. These findings define the cellular and spatial landscape of syndecan expression in healthy tissues and support SDC1 as an epithelial-enriched proteoglycan. These results also challenge the specificity of circulating SDC1 as a biomarker of endotheliopathy and raise the possibility that epithelial injury contributes substantially to circulating SDC1 after trauma and critical illness.

cell biology↗

Cytokinin regulates the gravitropic setpoint angle of seminal roots in barley and wheat

Plant root growth angle determines the spatial distribution of roots in soil and thereby influences access to water and nutrients when these resources are heterogeneously distributed. In barley, multiple seminal roots emerge at distinct gravitropic setpoint angles (GSAs) and they reliably re-establish their characteristic growth angles following reorientation, indicating robust intrinsic control. However, the molecular basis underlying GSA variation among roots within a single root system remains unknown. Here, we combined individual root type-specific transcriptomics with laser-capture microdissection to profile gravity-responsive zones (root cap, meristem, and elongation zone). We identified two CYTOKININ OXIDASE/DEHYDROGENASE (CKX) genes whose expression in the root cap was associated with root-specific GSA. Functional analysis showed that ckx mutants, which show higher cytokinin levels, exhibit significantly steeper seminal root GSAs, implicating cytokinin catabolism in root angle regulation. Consistent with this, exogenous cytokinin treatment induced a dose-dependent steepening in root angle in barley. Analyses of gravitropic curvature after gravistimulation further showed that ckx mutants exhibit altered gravitropic responses, indicating that CKX-mediated regulation of the root angle depends on gravity-responsive pathways. Notably, GSA-associated CKX expression patterns and cytokinin-dependent root angle responses were also observed in wheat, suggesting a conservation of this mechanism across cereals. Together, these findings identify cytokinin as a key regulator of root specific setpoint angles within a root system architecture, with potential implications for optimizing crop resource acquisition and yield.

plant biology↗

High-throughput genomic feature extraction reveals environmental adaptations of prokaryotes

Understanding the adaptations of microorganisms to their environment is key to predicting the stability and dynamics of microbial communities. To uncover molecular mechanisms of environmental response, we extracted genomic features from 13,554 prokaryotic isolates, and trained machine learning models to identify which ones are most strongly associated with the microbial salinity, temperature, oxygen, and pH preferences. To extract these features in high throughput, including gene families, non-coding RNAs (ncRNAs), oligonucleotides, and amino acid usage, we built FxTractor, a scalable and adjustable pipeline available at: https://github.com/MGXlab/FxTractor. We validated the performance of our models with experimental data from a newly isolated deep-sea extremophile belonging to the genus Limnochorda that is not well-represented among the ML training sets, showing strong agreement between predictions and the conditions used to isolate this strain. Our analysis revealed specific gene and ncRNA families associated with each of the four environmental parameters, uncovering both established and potentially new molecular mechanisms. Examples include the bacterial large Signaling Recognition Particle in isolates that are able to grow at high temperatures ([&ge;]55{degrees}C), suggesting a role in translational pausing and structural stability under thermal stress. We also found the anti-hemB ncRNA to be associated with low-salinity (<0.7% NaCl), indicating a conserved antisense mechanism regulating the energetic costs of heme biosynthesis. Together, these findings provide new insights into microbe-environment interactions, and show how FxTractor enables high throughput discovery of genomic associations.

bioinformatics↗

Early establishment acts as a selective filter shaping climate-associated genomic variation in European beech

Climate change is increasing drought and heat stress in European forests, raising concerns about the capacity of long-lived tree species to respond to rapidly changing environmental conditions. While local adaptation has been documented in many forest trees, it remains unclear whether newly established seedlings, which form the forests of the future, are able to persist and adapt to these new climatic conditions. Here, we investigated genomic differences between naturally regenerated seedlings and trees of European beech (Fagus sylvatica) across the three regions of the German Biodiversity Exploratories using low-coverage whole-genome sequencing (5x) of 1,032 individuals. Population structure was primarily driven by geographic region, whereas genetic diversity was similar across life stages. Despite this genome-wide similarity, we detected allele frequency shifts between trees and seedlings, concentrated in narrow genomic windows. These shifts were strongest in surviving seedlings, suggesting that environmental filtering during early establishment may contribute to shaping the genetic composition of regenerating populations. The strongest signals were observed within the Swabian Alb, where sampled seedlings were 2-years old and had experienced a longer period of potential filtering prior to sampling. Genotype - environment association analyses identified loci associated with climatic variables, and subsequent GO enrichment analyses of genes linked to these loci revealed significantly more enriched GO terms in seedlings than in trees, suggesting stronger environmental filtering by the current climate in seedlings. In particular, we found associations with maximum air temperature, relative humidity, soil moisture, and precipitation, affecting genes involved in stress responses, growth, metabolism, and developmental processes. Together, our results demonstrate that young cohorts of European beech differ genetically from trees and reveal genomic patterns consistent with life-stage-dependent environmental filtering. These findings suggest that the genetic composition of early life-stages is already altered by current environmental conditions, possibly contributing to adaptation to new climatic conditions.

ecology↗

Comparative epigenomics across the barley pangenome links structural variation to regulatory genome function

Structural variants (SVs) are abundant in plant genomes and influence agronomic traits, yet their regulatory interpretation remains challenging. Here, we combine pangenome-wide profiling of DNA methylation and chromatin accessibility across 20 barley genotypes, complemented by histone modification and chromatin interaction data in a subset of 10 genotypes. Comparative analysis of genotype-specific epigenomes reveals a globally conserved DNA methylation landscape across the barley pangenome alongside extensive regulatory variability at orthologous genes. We show that SVs do not broadly remodel global chromatin landscapes but instead act through context-dependent rewiring of local regulatory interactions. Despite this epigenomic stability, SVs may contribute to gene expression changes via chromatin contacts. Tissue-specific chromatin accessibility demonstrates that SV effects depend on developmental context. Integrating chromatin state variation with SVs at key vernalization genes explains epigenetic contributions to growth habit diversity. Together, these results provide a framework for interpreting the regulatory consequences of structural variation in crop genomes.

plant biology↗

Site-Specific Introduction of Non-Canonical Amino Acids into natural and engineered Non-Ribosomal Peptides

The incorporation of non-canonical amino acids (ncAAs) into proteins, developed in the past 20 years, has opened new avenues with respect to protein structure, protein modification, protein-protein interaction or enzyme catalysis beyond what is possible with the 20 proteinogenic AAs. Although >300 unusual building blocks including several ncAAs have been described in nonribosomal peptides (NRPs) naturally, we aimed to further expand the scope of the underlying nonribosomal peptide synthetases (NRPS) to incorporate ncAAs beyond the naturally available ones. We have therefore systematically screened for ncAA accepting NRPS systems, applied NRPS engineering to transfer the respective ncAA-accepting parts into other NRPSs and thereby created novel peptides that were further derivatized in post-enzymatic chemical synthesis reactions directly in bacterial culture extracts. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/738027v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@8968ddorg.highwire.dtl.DTLVardef@143a852org.highwire.dtl.DTLVardef@dfac73org.highwire.dtl.DTLVardef@b2c6fb_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Pan-genomic and pan-transcriptomic analysis of the Heavy Metal ATPase family reveals diverse expression patterns and functional roles in barley

Heavy metals act as essential metalloprotein cofactors in numerous physiological processes but can become toxic when non-essential metals accumulate or when essential metals are in excess. As plants continuously encounter heavy metals through their roots, they have evolved complex homeostatic mechanisms to regulate metal uptake and distribution. The Heavy Metal ATPase (HMA) gene family encodes a group of heavy metal transporting P-type ATPases that have been linked to stress resistance and nutrient supply. Here, we used a bioinformatics approach to identify and characterise 13 HMA genes containing characteristic P1B-type ATPase domains and motifs in the barley Morex V3 reference genome. The genes are located on five of the seven barley chromosomes. Phylogenetic analysis revealed that they cluster into five sub-clades, including one clade unique to barley. Expression profiling across multiple datasets showed distinct temporal and tissue-specific expression patterns among HvHMAs, with several members exhibiting significant transcriptional responses to specific biotic and abiotic stresses. By utilising recently available pan-transcriptomic and pan-genomic resources, we have identified substantial allelic diversity and inter-accession variation in HvHMAs. Our findings suggest that HvHMAs have functions extending beyond canonical heavy metal homeostasis and warrant further investigation for their potential roles in broader physiological and stress-related processes.

plant biology↗

Chromosome-Specific Expansion and Diversification of the Thionin Gene Family in Barley

Thionins are cysteine-rich peptides involved in plant defense. However, their genomic organization, evolutionary expansion, and potential function in barley remain unclear. Here, we integrated reference genome, pan-genome, and pan-transcriptome resources to systematically characterize the thionin gene family in barley. Fifty-six thionin genes were identified in the reference genome Morex V3, displaying pronounced chromosomal clustering and high sequence conservation consistent with extensive tandem duplication. Promoter analysis of these genes revealed enrichment of cis-acting elements associated with stress- and hormone-related signaling pathways, suggesting a potential role for thionins in biotic stress responses, including aphid defense, as suggested by previous studies. Analysis of 20 barley genotypes revealed substantial copy number variation, particularly on chromosomes 6H and 7H, indicating dynamic population-level expansion. Sequence-based clustering grouped thionins into ten clusters and five singletons, with major clusters corresponding to specific chromosomes. Integration of pan-transcriptome data showed that transcriptional activity was largely confined to four major clusters. Aphid infestation of four genotypes featuring copy number variation in chr 6H thionin genes resulted in a strong induction of thionin gene expression, with more pronounced responses during poor-host interactions. Aphid-induced expression tended to increase with thionin gene number, however, this no correlation was observed regarding basal gene expression levels. Together, these findings indicate that the thionin gene family in barley has undergone species-specific expansion driven by tandem duplication and contributes to genotype-dependent aphid defense responses.

Plant Biology↗

Whole genome sequencing and variant discovery in 344 global grasspea (Lathyrus sativus L.) lines

The rapid expansion of genomic data resources for major crops is opening new options for crop improvement, while resources for most underutilised crops lag behind, risking a widening gap in crop improvement. One of these underutilised crops is grasspea (Lathyrus sativus), an ancient crop with modern cultivation centred on South Asia and Ethiopia. We conducted whole genome shotgun sequencing on a global collection of 344 grasspea lines, producing over 152 billion reads. Following variant discovery and filtering we created a single nucleotide polymorphism (SNP) marker set of over 1.5 million SNPs. This is a resource of major significance for this crop which can help unlock its breeding potential through marker development and the identification of genes controlling agronomically important traits.

genomics↗

Assessment of a Passive Sampler for Aquifer Microbial Community Profiling and Comparison of Porous Media Applied in a Managed Recharge Scenario

Microbial communities play an important role in aquifer systems, as both hazards (e.g., pathogens, carriers of antibiotic resistance genes) and contributors to contaminant remediation. However, monitoring native microbial communities in situ remains challenging. To address this challenge, we developed a passive sampler with that employs removable cartridges containing solid media designed to re-create the aquifer environment in a controlled fashion and support consistent, repeatable, time-series sampling. With a bench-scale, continuous-loop setup circulating advanced-treated wastewater, we compared microbial community dynamics across three candidate porous media: native aquifer sediment, zirconia beads, and laboratory-grade silica sand. 16S rRNA gene amplicon sequencing revealed that native aquifer sediment best reflected influent microbial composition and temporal shifts. Native aquifer sediment also exhibited more spatial consistency in microbial diversity along the sampler. These findings suggest that native aquifer sediment is an optimal porous medium for long-term, in situ monitoring of microbial communities for managed aquifer recharge and other applications in groundwater systems.

ecology↗

Environmental DNA Reveals Reykjavik's Human and Ecological History

Iceland was among the last large islands settled by humans, with colonization (Landnam) in the late 9th century CE (Common Era) and is often portrayed as an ecological disaster driven by the Norse settlers. Here, we revisit this narrative through environmental DNA (eDNA) and multiproxy analyses of sediment cores from Lake Tjornin in central Reykjavik, one of Icelands earliest and longest-occupied settlements. Originally a marine embayment, Tjornin became a freshwater lake around 660 CE. Our record reveals a human presence decades before the long-accepted arrival date of 877 CE, marked by the Landnam volcanic tephra. Early settlement brought livestock, barley cultivation, and other introduced taxa that enhanced nutrient cycling and unexpectedly increased local biodiversity. Contrary to the conventional view of rapid deforestation, eDNA shows that birch and willow expanded during the settlement period, likely supported by deliberate management. Pronounced ecological and land use shifts occurred after 1200 CE, but these were coeval with the Little Ice Age cooling, compounded by volcanic eruptions, storm surges, and plague, rather than anthropogenic degradation. Crop cultivation ceased, arboreal taxa retracted, and grazing pressure maintained open landscapes. Even more profound ecological changes came after c. 1750 CE with urbanization and industrialization, as wastewater discharge, heavy-metal pollution, and fossil fuel use reshaped Tjornins ecosystem. These findings challenge the prevailing model of Norse-induced environmental collapse, revealing instead a dynamic human-environment relationship shaped by both cultural practices and external stressors. By applying eDNA to a long-occupied urban catchment, we demonstrate the power of genomic methods to refine settlement chronologies, reassess ecological baselines and changes, and integrate natural and cultural histories. This approach offers a model for revisiting human-environment interactions in urban centers worldwide.

genomics↗

Barley BODYGUARD controls cuticular specialisations regulated by SHINE transcription factors

The outer epidermis of land plants secretes a cuticular layer, a hydrophobic diffusion barrier which minimises water loss into the atmosphere and protects from pests, ultraviolet light and organ fusion. Cuticles typically comprise a polyester cutin matrix embedded and overlaid with cuticular waxes, but their exact chemical make-up, structure and functions can vary widely depending on the tissue and species. Barley shows two such cuticular specialisations: (1) deposition of a thick {beta}-diketone-rich wax bloom on multiple organs at reproductive stage, common in other Poeceae species and linked to yield; and, (2) secretion of a sticky layer on the grain fruit (caryopsis) pericarp cuticle which adheres to inner floral hulls, leading to barleys distinctive covered grain used in animal feed and malting. Two SHINE/WAX-INDUCER transcription factors in barley, HvWIN1 and NUD, promote the wax bloom and hull to caryopsis adhesion, respectively, yet little is understood about other genes involved. Leveraging near-isogenic lines of wax-deficient mutants, we identify the barley BODYGUARD1 (HvBDG1) gene encoding an /{beta}-hydrolase essential for leaf cuticular integrity and wax bloom deposition. Modelling of functional and defective alleles suggests that HvBDG1 N-terminal region control of protein flexibility is important for HvBDG1 function. In addition to their role in controlling barley epicuticular wax deposition, we show that both HvBDG1 and HvWIN1 are essential for strong hull to caryopsis adhesion. Along with NUD, these gene products differentially contribute to ultrastructural changes on the pericarp associated with a cuticular building programme driven by NUD and HvWIN1 regulation of cuticle metabolism and transport and cell wall-related genes, and correlate with shifts in pericarp surface chemistry. We also show that the previously asserted grain-specific role of NUD should be revised, as our findings reveal that it is essential for maintaining leaf cuticle integrity. Our analyses in barley suggest that NUD and HvWIN1 control cuticular specialisations and cuticle integrity in part via promotion of HvBDG1 expression, while HvWIN1 and NUD likely act independently from each other. Lastly, mining tetraploid wheat mutant populations followed by crossing to combine mutated homoeologues demonstrated that BDG1 and WIN1 orthologues also control wax bloom in wheat. Taken together, our work greatly expands the genetic networks and molecular activities important for cuticle development in cereals and the underlying mechanisms for both shared and species-specific cuticular specialisations.

plant biology↗

Twist and Scout: Analysis and Curation of Particles in Cryo-Electron Tomography Using TANGO

Cryo-electron tomography (cryo-ET) enables the visualization of cellular structures in near-native environments, but its potential for spatial analysis has been underutilized due to a lack of versatile tools accommodating biological sample diversity. Available solutions often rely on case-specific or hypothesis-driven approaches, while holistic analyses remain challenging. In this work, we introduce TANGO (Twist-Aware Neighborhoods for Geometric Organization), a novel framework leveraging point cloud descriptors to analyze spatial arrangements of particles, such as macromolecular complexes, in cryo-ET. By encoding relative positions and orientations of particles as twist vectors, TANGO enables rotationally invariant feature extraction, including structured neighborhood occupancy, lattice topology, or angular deviations. Its modular design and user-friendly interface allow for customization of features, facilitating exploratory analyses of spatial patterns in diverse experimental datasets. With its open-source Python implementation, TANGO advances the ability to decode complex cellular architectures and their functional relationships, offering a valuable tool for the cryo-ET community.

molecular biology↗

Post-Domestication selection of MKK3 Shaped Seed Dormancy and End-Use Traits in Barley

Anthropogenic selection of grain traits such as dormancy has shaped the developmental trajectories of crop plants (1). In cereals, shortening dormancy provides rapid and even post-harvest germination, but increases the risk of weather-induced pre-harvest sprouting (PHS) with harvest losses estimated at beyond 1 billion USD a year (2, 3, 4). Our understanding of how, why, when and where diversification of cereal dormancy arose is fragmentary. Here, we show in the founder cereal crop barley (Hordeum vulgare) that the Mitogen-Activated Protein Kinase (MAPK) pathway regulates dormancy primarily through a mosaic of locus haplotypes comprising copy-number variation and inherent kinase activity of Mitogen-activated protein kinase kinase 3 (MKK3). We provide evidence supporting the historical selection of specific MKK3 haplotypes that shape dormancy levels according to changing climatic pressures. Understanding the regulatory landscape of MKK3 provides a genetic framework to balance short grain dormancy and PHS-avoidance during a period of rapid climate change.

plant biology↗

Molecular architecture of heterochromatin at the nuclear periphery of primary human cells

In eukaryotes, meters of DNA are packaged into micrometer scale nuclei. Nucleosomes, as the major organizational unit, have been extensively studied in vitro, yet the elaborate 3D structure of chromatin inside cells and its distinct multi-nucleosome arrangements remain poorly resolved. Here, we combine cryo-electron tomography with template matching, subtomogram averaging and molecular simulations to visualize nucleosomes and chromatin structure inside human cells. We confidently assign individual nucleosomes and report their in-situ structure at secondary structure resolution. By tracing linker DNA, we identify multi-nucleosome arrangements and uncover higher-order chromatin structures in situ, including a 37-nm wide, elongated but non-fibrous arrangement. In situ structural biology thus reveals the molecular chromatin organization inside cells and sets the stage for 3D genomics.

biophysics↗

Enhanced sensitivity of TAPscan v4 enables comprehensive analysis of streptophyte transcription factor evolution

Transcription associated proteins (TAPs) fulfill multiple functions in regulatory and developmental processes and display lineage-specific evolution. TAPscan is a comprehensive and highly reliable tool for genome-wide TAP annotation via domain profiles. Here, we present TAPscan v4, including an updated web interface (https://tapscan.plantcode.cup.uni-freiburg.de/), which enables an in-depth representation of the distribution of 138 TAP families across 678 species from diverse groups of organisms, with a focus on Archaeplastida (plants in the wide sense). With this release, we also make the underlying "Genome Zoo" available, a curated protein data set with scripts and metadata. 18 new TAP (sub)families were added as part of the update. Nine of those were gained in the most recent common ancestor of the Streptophyta (comprising streptophyte algae and land plants), or within the streptophyte algae. More than one-third of all detected TAP family gains were identified during the evolution of streptophyte algae, before the emergence of land plants, and are thus likely to have been significant for plant terrestrialization. The TAP complement of the Zygnematophyceae was identified to be the most similar to that of land plants, consistent with the finding that this lineage is sister to land plants. Overall, our data retrace the evolution of streptophyte TAPs, allowing us to pinpoint the regulatory repertoire of the earliest land plants.

bioinformatics↗

The RAD51 paralogue HvXRCC2 regulates meiosis and recombination in barley

Using a positional candidate-gene approach we show that semi-sterile desynaptic8 mutants are associated with deletions in or complete knockout of the barley homolog of XRCC2 (X-Ray Repair Cross Complementing 2). In barley XRCC2 mutants, the initial meiotic progression is normal, albeit with a small delay in initiation, with completion of synapsis. However, the absence of HvXRCC2 subsequently leads to a dramatic reduction in the number of crossovers, chromosome mis-segregation, and infertility, suggesting that HvXRCC2 plays a major role in recombination. This mutant phenotype is congruent with that reported in mammalian studies but contrasts with the XRCC2 mutant in Arabidopsis which is fertile, exhibits normal chromosome pairing and correct chromosome segregation, and is associated with an increased rate of crossovers. This indicates that the XRCC2 mutant phenotype in Arabidopsis is not representative of all plants and that XRCC2 is not a good candidate for the modulation of recombination in barley. HighlightThe mutants of the barley homolog of XRCC2 exhibit delays in replication leading to defective meiosis, altered RAD51 orthologue behaviour, and significant reduction in the number of crossovers as in canonical mammalian XRCC2 mutants but unlike those in Arabidopsis.

plant biology↗

Genomic resources for a historical collection of cultivated two-row European spring barley genotypes.

Barley genomic resources are increasing rapidly, with the publication of a barley pangenome as one of the latest developments. Two-row spring barley cultivars are intensely studied as they are the source of high-quality grain for malting and distilling. Here we provide data from a European two-row spring barley population containing 209 different genotypes registered for the UK market between 1830 to 2014. The dataset encompasses RNA-sequencing data from six different tissues across a range of barley developmental stages, phenotypic datasets from two consecutive years of field-grown trials in the United Kingdom, Germany and the USA; and whole genome shotgun sequencing from all cultivars, which was used to complement the RNA-sequencing data for variant calling. The outcomes are a filtered SNP marker file, a phenotypic database and a large gene expression dataset providing a comprehensive resource which allows for downstream analyses like genome wide association studies or expression associations.

plant biology↗