Biology subjects

Riedl, M.

Publications and source records attributed to Riedl, M..

7 recordsLinked to original sources

bioRxiv2026

MCBO: Mammalian Cell Bioprocessing Ontology, A Hub-and-Spoke, IOF-Anchored Application Ontology

Mammalian cell-based biopharmaceutical manufacturing generates vast, heterogeneous datasets that remain fragmented due to the lack of a standardized metadata framework. A key challenge in biologics manufacturing is linking bioreactor conditions, cell line characteristics and recombinant product production. A datahub for mammalian cell bioprocessing, integrated by semantic technologies, will serve as a tool to understand and query the connections between these complex datasets. While existing ontologies cover general biological and experimental concepts, they often lack the operational specificity required to harmonize bioreactor conditions, cell line engineering, and product quality metrics. To address this specific gap, we present the Mammalian Cell Bioprocessing Ontology (MCBO), a hub-and-spoke application ontology built on Basic Formal Ontology (BFO) foundations and anchored to the Industrial Ontology Foundry (IOF) Core. MCBO formalizes the process-participant-quality modeling pattern, enabling precise tracking of culture environmental conditions as qualities of the physical culture system. We demonstrate the utility of MCBO through a central datahub populated with 723 curated cell culture process instances and 325 unique bioprocess samples from published studies. The framework is validated against eight competency questions implemented via SPARQL, demonstrating efficient cross-study querying of culture optimization, cell line engineering, and multi-omics integration. By providing a stable, schema-independent substrate for data harmonization, MCBO enables AI agent-powered, human-in-the-loop workflows and facilitates LLM-assisted extraction of structured metadata from legacy records. MCBO is open-source and designed for deployment behind institutional firewalls to support interoperable biomanufacturing intelligence while maintaining intellectual property sensitivity. MCBO is supported by the International Biomanufacturing Network (IBioNe), which aims to accelerate discoveries and developments by providing a network of biomanufacturing training and workforce development to educate the next generation of biomanufacturing experts. MCBO is evaluated using over 700 curated cell culture processes, validated against eight competency questions, and quality-controlled using automated ontology checks. Evaluation results and formal reasoning validation are provided in the Supplementary Materials. Availability: https://github.com/lewiscelllabs/mcbo

bioinformatics↗

bioRxiv2025

Chronic alcohol drinking delays recovery from capsaicin- and nerve injury-induced hypersensitivity in mice

Chronic pain and alcohol use disorder (AUD) are major health concerns that significantly impair quality of life. Persistent pain is common in individuals with alcohol dependence, and alcohol is commonly used by chronic pain patients for self-medication. The neural mechanisms linking these conditions remain unclear. We hypothesized that chronic alcohol exposure induces hypersensitivity in multiple modalities and increases the duration of recovery in acute and persistent pain models. Using the two-bottle free-choice alcohol consumption paradigm in adult mice, alcohol-induced hypersensitivity (AIH), indicated by reduced mechanical withdrawal thresholds, developed after 4-6 weeks of alcohol consumption compared to age- and sex-matched water-consuming controls. Alcohol-consuming female mice, but not male mice, developed cold hypersensitivity after AIH emerged. To assess the impact of chronic alcohol consumption on acute and persistent pain, we used intraplantar capsaicin and sciatic nerve crush models, respectively. In the capsaicin model, water-treated, but not alcohol-treated, mice recovered from hypersensitivity by 24 hours post-injection. In the sciatic nerve crush model, alcohol-consuming mice exhibited slower recovery of mechanical withdrawal thresholds compared to water-consuming controls. While mechanical hypersensitivity in water-consuming mice returned to pre-surgical thresholds by 3-4 weeks post-surgery, recovery in alcohol-consuming mice was both delayed and partial. Surgical intervention did not impact alcohol intake. Overall, our results suggest that chronic voluntary alcohol consumption facilitates the transition to chronic pain by prolonging hypersensitivity and delaying recovery from injuries. HighlightsO_LIMagnitude of alcohol-induced mechanical hypersensitivity is similar across sex C_LIO_LIFemales, but not males, develop alcohol-induced cold sensitivity C_LIO_LIChronic alcohol prolongs acute inflammatory pain C_LIO_LIChronic alcohol prolongs nerve-injury induced neuropathic pain C_LI

pharmacology and toxicology↗

bioRxiv2025

A genome-scale CRISPR deletion screen in Chinese Hamster Ovary cells reveals essential regions of the coding and non-coding genome

The biopharmaceutical sector relies on CHO cells to investigate biological processes and as the preferred host for production of biotherapeutics. Simultaneously, advancements in CHO cell genome assembly have provided insights for developing sophisticated genetic engineering strategies. While the majority of these efforts have focused on coding genes, with some interest in transcribed non-coding RNAs (e.g., microRNAs and lncRNAs), there remains a lack of genome-wide systematic studies that precisely examine the remaining 90% of the genome. This unannotated "dark matter" includes regulatory elements and other, poorly understood or characterized functionality of the genome that may be potentially critical for cell survival. In this study, we deployed a genome-scale CRISPR screening platform with 112,272 paired guide RNAs targeting 14,034 genomic regions for complete deletion of 150 kb long sections. This platform enabled the execution of a negative screen that selectively identified dying cells to determine regions essential for cell survival. By using paired gRNAs, we overcame the intrinsic limitations of traditional frameshift strategies, which will likely have little or no effect on the non-coding genome. This study revealed 427 regions essential for CHO survival, many of which currently lack gene annotation or known function. For these regions we present annotation status, transcriptional activity as well as annotated chromatin states such as enhancers. Selected regions, specifically those that were negative for all the above, were individually deleted for confirmation. This work sheds a novel light on a substantial part of the mammalian genome which is traditionally difficult to investigate and therefore, neglected.

cell biology↗

bioRxiv2024

Global coordination of protrusive forces in migrating immune cells

Efficient immune responses rely on the capacity of leukocytes to traverse diverse and complex tissues. To meet such changing environmental conditions, leukocytes usually adopt an amoeboid configuration, utilizing their forward-positioned nucleus as a probe to identify and follow the path of least resistance among pre-existing pores. We show that in dense environments, where even the largest pores preclude free passage, leukocytes switch polarity and position their nucleus behind centrosome and organelles. In this mesenchymal configuration, local compression of the cell body triggers assembly of a central F-actin pool, located between cell front and nucleus. Central actin pushes outward to transiently dilate a path for organelles and nucleus. Pools of central and front actin are tightly coupled and experimental depletion of the central pool enhances actin accumulation and protrusion formation at the cell front. Although this shifted balance speeds up cells in permissive environments, migration in restrictive environments is impaired, as the unleashed leading edge dissociates from the trapped cell body. Our findings establish an actin regulatory loop that balances path dilation with advancement of the leading edge to maintain cellular coherence.

cell biology↗

bioRxiv2022

Synchronization in collectively moving inanimate and living active matter

Regardless of whether one considers swarming insects, flocking birds, or bacterial colonies, collective motion arises from the coordination of individuals and entails the adjustment of their respective velocities. In particular, in close confinement, such as those encountered by dense cell populations during development or regeneration, collective migration can only arise coordinately. Yet, how individuals unify their velocities is often not understood. Focusing on a finite number of cells in circular confinements, we identify waves of polymerizing actin that function as a pacemaker governing the speed of individual cells. We show that the onset of collective motion coincides with the synchronization of the wave nucleation frequencies across the population. Employing a simpler and more readily accessible mechanical model system of active spheres, we identify the essential requirements to reach the corresponding collective state, i.e. the synchronization of the individuals internal oscillators. The mechanical toy experiment illustrates that the global synchronous state is achieved by nearest neighbor coupling. We suggest by analogy that local coupling and the synchronization of actin waves are essential for emergent, self-organized motion of cell collectives.

biophysics↗

bioRxiv2022

Tissue-wide Effects Overrule Cell-intrinsic Gene Function in Cortical Projection Neuron Migration

The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation is based on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps that are regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not well understood. Here, we utilized Mosaic Analysis with Double Markers (MADM) technology to either sparsely or globally delete gene function followed by quantitative single cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically impacts the overall migration phenotype of individual cortical projection neurons. In a broader context our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development (FMCD) in particular, and neurological diseases in general. LAY SUMMARYThe assembly of the mammalian brain is a complex process and depends on tightly regulated developmental and genetic programs. The coordinated process of nerve cell (neuron) migration is essential to home neurons into their correct position which is vital for normal brain development. Disturbance of the neuron migration process at any point of development leads to severe brain malformations which result in devastating disease. To date, studies have mainly focused on cell-intrinsic gene functions controlling neuronal migration. Therefore, very little is known about the possible contribution of the cellular surrounding and tissue-wide effects. The scale and nature of such global tissue-wide effects remain completely unclear. We thus established genetic platforms based on Mosaic Analysis with Double Markers (MADM) to visualize and quantify tissue-wide effects in a defined genetic context and at single cell resolution. We found a critical predominant role of the genetic landscape and state of cellular environment affecting overall neuron migration properties. In a broader context our results suggest that global tissue-wide effects are a major component of the underlying etiology of neurological diseases such as focal malformations of cortical development (FMCD).

neuroscience↗

bioRxiv2021

Mechanosensitivity of amoeboid cells crawling in 3D

Efficient immune-responses require migrating leukocytes to be in the right place at the right time. When crawling through the body amoeboid leukocytes must traverse complex three-dimensional tissue-landscapes obstructed by extracellular matrix and other cells, raising the question how motile cells adapt to mechanical loads to overcome these obstacles. Here we reveal the spatio-temporal configuration of cortical actin-networks rendering amoeboid cells mechanosensitive in three-dimensions, independent of adhesive interactions with the microenvironment. In response to compression, Wiskott-Aldrich syndrom protein (WASp) assembles into dot-like structures acting as nucleation sites for actin spikes that in turn push against the external load. High precision targeting of WASp to objects as delicate as collagen fibers allows the cell to locally and instantaneously deform its viscoelastic surrounding in order to generate space for forward locomotion. Such pushing forces are essential for fast and directed leukocyte migration in fibrous and cell-packed tissues such as skin and lymph nodes. In BriefWASp-driven actin spikes counter compressive loads of crowded tissue-landscapes.

cell biology↗