Biology subjects

Gabriel, E.

Publications and source records attributed to Gabriel, E..

8 recordsLinked to original sources

bioRxiv2026

Survival of Streptococcus anginosus in blood is linked to hydrogen peroxide production

Streptococcus anginosus is an opportunistic pathogen causing bacteremia, respiratory tract infections, abscesses, odontogenic infections and has recently been associated with gastric cancer. While numerous genes encoding putative virulence factors have been detected in whole genome sequences, a detailed molecular characterization is missing for most of them. To address putative virulence determinants, we investigated hydrogen peroxide production by S. anginosus and assessed its functional significance for survival in human blood. In Streptococcus pneumoniae the pyruvate oxidase, encoded by the spxB gene, is responsible for H2O2 production and represents a major virulence factor. Interestingly, S. anginosus harbors two genetic variants of the spxB gene, one with high homology to the S. pneumoniae spxB (sequence identity: approx. 94 %) gene, while the other appears to be specific for S. anginosus. Strains carrying the S. pneumoniae variant demonstrate higher H2O2 production (10-20 M) compared to strains harboring the anginosus variant (<1 M). Incubation of S. anginosus strains in human blood showed that bacterial survival was correlated to the amount of hydrogen peroxide production. Assessing H2O2 production in an S. anginosus strain carrying a deletion of the CcpA regulator revealed the control of spxB and H2O2 production by carbon catabolite repression. In conclusion, we found evidence for the presence of a major S. pneumoniae virulence factor in S. anginosus, and we were able to demonstrate that it increases the ability of S. anginosus to survive in human blood.

microbiology↗

bioRxiv2026

Quantitative 3D cytoarchitecture of human brain organoids using light-sheet microscopy

Human brain organoids are valuable models for studying human brain development and disorders. Although organoids enable multi-omics analyses, understanding developmental mechanisms requires precise three-dimensional mapping of cell types and their dynamics within their cytoarchitecture. Traditional thin-section immunohistochemistry and imaging provide insights but disrupt spatial information. Light-sheet microscopy allows volumetric imaging of intact organoids, but methods and analytical algorithms remain technically challenging. Here, we introduce LUCID-org, an optimized and reproducible technique for Light-sheet imaging of Unsectioned, Cleared, Immunolabeled, and Depth-resolved human brain organoids. Coupled with machine-learning-based quantitative analysis, LUCID-org enables unbiased 3D characterization of cell-type composition and cytoarchitecture. We validated this approach using brain organoids derived from a patient with CENPJ-mutated microcephaly, revealing quantifiable defects in the ventricular zone (VZ), progenitor density, dynamics, cell-type variability, VZ lumen volume, and neuronal distribution compared with healthy controls. The LUCID-org pipeline is straightforward, taking approximately one week, significantly cheaper, non-toxic, and compatible with standard light-sheet microscopes. Therefore, the LUCID-org method could serve as a benchmark for comprehensive 3D analysis of human brain organoids.

developmental biology↗

bioRxiv2025

CCB79 is a primate-specific cilium initiation factor essential to maintain neural progenitor diversity in developing brain tissue.

Identifying the genes that regulate the accurate spatiotemporal diversity of neural progenitor cells (NPCs) helps to understand the mechanisms of human neocortex expansion. In primate brains, an additional intermediate progenitor layer, the outer subventricular zone (oSVZ), facilitates the expansion of the neocortex. Here, we identify an uncharacterized gene, KIAA0408, and show that its expression is enriched in intermediate progenitors. Removing KIAA0408 in human-induced pluripotent stem cell (iPSC)-derived brain organoids results in an impaired cortical organization characterized by abnormal cell fate and patterning defects, including the depletion of intermediate and ventral progenitors. Molecularly, KIAA0408 codes for a 79-kilodalton centriolar distal appendage protein (DAP) that controls cilium biogenesis (hereafter CCB79). CCB79 forms a complex with other DAP components and specifically localizes in the DAP at the onset of ciliogenesis, and its absence blocks ciliogenesis. Mechanistically, progenitors in 3D brain tissues are unable to form cilia, which induces aberrant hedgehog signaling and causes premature differentiation. Finally, human CCB79, rather than the mouse ortholog, rescues cilia defects, suggesting that CCB79 has undergone rapid evolution from rodents to primates to fine-tune ciliogenesis for proper brain development.

neuroscience↗

bioRxiv2023

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion, and drug screening

Brain organoids offer unprecedented insights into brain development and disease modeling and hold promise for drug screening. Significant hindrances, however, are morphological and cellular heterogeneity, inter-organoid size differences, cellular stress, and poor reproducibility. Here, we describe a method that reproducibly generates thousands of organoids across multiple iPSC lines. These High Quantity brain organoids (Hi-Q brain organoids) exhibit reproducible cytoarchitecture, cell diversity, and functionality, are free from ectopically active cellular stress pathways, and allow cryopreservation and re-culturing. Using patient-derived Hi-Q brain organoids, we recapitulated distinct forms of microcephaly pathogenesis: primary microcephaly due to a mutation in centrosomal CDK5RAP2 and progeria-associated microcephaly in Cockayne syndrome. When modeling glioma invasion, hi-Q brain organoids displayed a similar invasion pattern for a given patient-derived glioma cell line. This enabled a medium-throughput screen to identify Selumetinib and Fulvestrant, which also perturbed glioma invasion in vivo. Thus, the Hi-Q approach can easily be adapted to reliably harness brain organoids utility for personalized disease modeling and drug discovery.

cell biology↗

bioRxiv2021

Spatio-temporal point processes as meta-models for population dynamics in heterogeneous landscapes

Landscape heterogeneity affects population dynamics, which determine species persistence, diversity and interactions. These relationships can be accurately represented by advanced spatially-explicit models (SEMs) allowing for high levels of detail and precision. However, such approaches are characterised by high computational complexity, high amount of data and memory requirements, and spatio-temporal outputs may be difficult to analyse. A possibility to deal with this complexity is to aggregate outputs over time or space, but then interesting information may be masked and lost, such as local spatio-temporal relationships or patterns. An alternative solution is given by meta-models and meta-analysis, where simplified mathematical relationships are used to structure and summarise the complex transformations from inputs to outputs. Here, we propose an original approach to analyse SEM outputs. By developing a meta-modelling approach based on spatio-temporal point processes (STPPs), we characterise spatio-temporal population dynamics and landscape heterogeneity relationships in agricultural contexts. A landscape generator and a spatially-explicit population model simulate hierarchically the pest-predator dynamics of codling moth and ground beetles in apple orchards over heterogeneous agricultural landscapes. Spatio-temporally explicit outputs are simplified to marked point patterns of key events, such as local proliferation or introduction events. Then, we construct and estimate regression equations for multi-type STPPs composed of event occurrence intensity and magnitudes. Results provide local insights into spatio-temporal dynamics of pest-predator systems. We are able to differentiate the contributions of different driver categories (i.e., spatio-temporal, spatial, population dynamics). We highlight changes in the effects on occurrence intensity and magnitude when considering drivers at global or local scale. This approach leads to novel findings in agroecology where the organisation of cultivated fields and semi-natural elements are known to play a crucial role for pest regulation. It aids to formulate guidelines for biological control strategies at global and local scale.

ecology↗

bioRxiv2021

Human brain organoids assemble functionally integrated bilateral optic vesicles

During embryogenesis, optic vesicles develop from the diencephalon via a complex process of organogenesis. Using iPSC-derived human brain organoids, we attempted to simplify the complexities and demonstrate the formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day thirty, brain organoids could assemble optic vesicles, which progressively develop as visible structures within sixty days. These optic vesicle-containing brain organoids (OVB-Organoids) constitute a developing optic vesicles cellular components, including the primitive cornea and lens-like cells, developing photoreceptors, retinal pigment epithelia, axon-like projections, and electrically active neuronal networks. Besides, OVB-Organoids also display synapsin-1, CTIP-positive, myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photoreceptor activity of OVB-Organoids, and light sensitivities could be reset after a transient photo bleach blinding. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow conducting interorgan interaction studies within a single organoid.

developmental biology↗

bioRxiv2021

More pests but less treatments: ambivalent effect of landscape complexity on Conservation Biological Control

In agricultural landscapes, the amount and organization of crops and semi-natural habitats (SNH) have the potential to promote a bundle of ecosystem services due to their influence on ecological community at multiple spatio-temporal scales. SNH are relatively undisturbed and are often source of complementary resources and refuges, supporting more diverse and abundant natural pest enemies. However, the nexus of SNH proportion and organization with pest suppression is not trivial. It is thus crucial to understand how the behavior of pest and auxiliary species, the underlying landscape structure, and their interaction may influence conservation biological control (CBC). Here, we develop a generative stochastic landscape model to simulate realistic agricultural landscape compositions and configurations of fields and linear elements. Generated landscapes are used as spatial support over which we simulate a spatially explicit predator-prey dynamic model. We find that SNH boost predator population, but predator movement from hedges to fields is fundamental for an efficient pest regulation by auxiliaries and to decrease pesticide treatments. Moreover landscape elements may lead to different effects on pest reduction depending on the considered scale. Integration of species behaviors and traits with landscape structure at multiple scales are needed to provide useful insights for CBC.

ecology↗

bioRxiv2020

SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects

COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Dusseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19. One sentence summaryCOVID-19 modeling in human brain organoids

cell biology↗