Biology subjects

Adiba, S.

Publications and source records attributed to Adiba, S..

8 recordsLinked to original sources

bioRxiv2026

Transcriptional coupling of metabolism and cell mechanics controls humanneuroepithelium morphogenesis

Tissue morphogenesis integrates developmental programs with cell mechanics, yet the mechanisms coupling these processes remain poorly understood. We investigated this link during neuroepithelial morphogenesis in human iPSC-derived dorsal spinal organoids. We found that PAX3, a transcription factor whose loss causes neural tube defects, promotes force-bearing adherens junction assembly. It does so by driving apical clustering of N-cadherin complexes, thereby enabling neuroepithelial morphogenesis, a function conserved in the mouse neural tube. Transcriptomic, metabolomic, and functional analyses show that PAX3 sustains upper glycolysis and the associated mannose-dependent glycosylation pathways. Exogenous mannose rescues cadherin clustering and adherens junction mechanics following PAX3 loss, whereas inhibition of glycolysis or glycosylation recapitulates these defects. These findings establish mannose metabolism as a PAX3-regulated pathway conferring mechanical competence to developing tissues.

developmental biology↗

bioRxiv2024

Continuous emergence of phototaxis in Dictyostelium discoideum

The evolutionary transition from uni- to multicellularity is associated with new properties resulting from collective cell behavior. The social amoeba Dictyostelium discoideum alternating between individual cells and multicellular forms of varying size provides a powerful biological system to characterize such emergent properties. Multicellular forms coined slugs have long been described as chemotactic towards cAMP, and also as phototactic. While chemotaxis is also well-documented at the single-cell level, which merely explains slug chemotaxis, we asked whether slug phototaxis is an emergent property of multicellularity. For this, we developed an automated microscopy setup to quantify and compare the migration trajectories of single cells and slugs moving in the dark or illuminated with lateral light. We find that single cells, either extracted from phototactic slugs or taken prior to multicellular aggregation, are not phototactic, implying that slug phototaxis results from interactions between cells that lack this property. Further, by analysing slugs composed of a varying number of cells, we find that phototaxis efficiency increases continuously with slug size. Cell-cell interactions combined with self-organization are thus key elements for this property to emerge.

evolutionary biology↗

bioRxiv2024

Environmentally-informed functional characterization of a plastid diatom metabolic bridge of mitochondrial origin

Withdrawal statementThe authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2022/507166. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2022.09.08.507166

evolutionary biology↗

bioRxiv2023

Anchoring of parasitic plasmids to inactive regions of eukaryotic chromosomes through nucleosome signal

Natural plasmids are common in prokaryotes but few have been documented in eukaryotes. The natural 2{micro} plasmid present in budding yeast Saccharomyces cerevisiae is one of the most well characterized. This highly stable genetic element coexists with its host for millions of years, efficiently segregating at each cell division through a mechanism that remains poorly understood. Using proximity ligation (Hi-C, Micro-C) to map the contacts between the 2{micro} and yeast chromosomes under dozens of different biological conditions, we found that the plasmid tether preferentially on regions with low transcriptional activity, often corresponding to long inactive genes. Common players in chromosome structure such as members of the structural maintenance of chromosome complexes (SMC) are not involved in these contacts which depend instead on a nucleosomal signal associated with a depletion of RNA Pol II. These contacts are stable throughout the cell cycle, and can be established within minutes. This strategy may involve other types of DNA molecules and species other than S. cerevisiae, as suggested by the binding pattern of the natural plasmid along the silent regions of the chromosomes of Dictyostelium discoideum.

genomics↗

bioRxiv2022

Single-cell phenotypic plasticity modulates social behaviour in Dictyostelium discoideum.

In Dictyostelium chimeras, strains social behaviour is defined based on their relative representation in the spores - the reproductive cells resulting from development - referred to as spore bias. Some strains, called cheaters, display systematically positive spore bias in chimeras and are considered a threat to the evolutionary stability of multicellular organization. The selective advantage gained by cheaters is indeed predicted to undermine collective functions whenever social behaviours are genetically determined. However, genotypes are not the only determinant of spore bias, and the relative role of genetic and plastic phenotypic differences in strains evolutionary success is unclear. Here, we control phenotypic heterogeneity by harvesting cells in different growth phases, and study the effects of plastic variation on spore bias in chimeras composed of isogenic or genetically different populations. Spore bias is shown to depend both on growth phase and on population composition, and to be negatively correlated to the fraction of loners, i.e. cells that do not join aggregates. We examined several single-cell mechanical properties that are expected to affect aggregation efficiency, and found that variations in the fraction of slowly moving cells with growth phase may explain why earlier cultures appear to be underrepresented in the spores. The involvement of a go-or-grow mechanism during cell aggregation is also consistent with known variations of cell-cycle phase distribution during population growth. We confirm the expected ubiquity of growth-phase induced spore bias variation by showing that it is not negligible in genetic chimeras, and can even reverse the classification of a strains social behaviour. These results suggest that aggregation can provide an efficient lottery system to harness the evolutionary spread of cheaters.

evolutionary biology↗

bioRxiv2022

A Plastidial Glycolytic-Gluconeogenic Switch of Mitochondrial Origin Enables Diatom Adaptations to High Latitudes

Organic carbon fixed in chloroplasts through the Calvin Cycle can be diverted towards different metabolic fates, including cytoplasmic and mitochondrial respiration; gluconeogenesis; and synthesis of diverse plastid metabolites via the pyruvate hub. In plants, pyruvate is principally produced via cytoplasmic glycolysis, although a plastid-targeted lower glycolytic pathway is known in non-photosynthetic tissue. Here, we characterize a lower plastid glycolytic-gluconeogenesis pathway in diatoms, ecologically important marine algae distantly related to plants. We show that two reversible enzymes required to complete diatom plastid glycolysis-gluconeogenesis, Enolase and PGAM (bis- phospho-glycerate mutase), originated through duplications of mitochondria-targeted respiratory isoforms. Through CRISPR-Cas9 mutagenesis, integrative omic analyses, and measured kinetics of expressed enzymes in the diatom Phaeodactylum tricornutum, we present evidence that this pathway diverts plastid glyceraldehyde-3-phosphate into the pyruvate hub, and may also function in the gluconeogenic direction. Considering experimental data, we show that this pathway has different roles dependent in particular on day length and environmental temperature, and show that it is expressed at elevated levels in high latitude oceans where diatoms are abundant. Our data provide evolutionary, meta-genomic and functional insights into a poorly understood yet evolutionarily recurrent plastid metabolic pathway.

plant biology↗

bioRxiv2022

Variable effects on virulence of bacteriophage resistance mechanisms in extraintestinal pathogenic Escherichia coli

AO_SCPLOWBSTRACTC_SCPLOWBacteria exposed to killing agents such as antibiotics or viruses develop resistance. While phage therapy, the use of bacteriophages (phages) for treating bacterial infections, is proposed to answer the antibiotic resistance crisis, bacterial resistance to phages remains poorly characterized during phage treatment. We studied a large population of phage-resistant extra-intestinal pathogenic Escherichia coli 536 clones emerging from both in vitro (non-limited liquid medium) and in vivo (murine pneumonia) conditions. Genome sequencing revealed a mutational convergence of phage resistance mechanisms towards the modification of two cell-wall components, the K15 capsule and the LPS, whatever the condition, showing that their identification could be predicted from the in vitro conditions. The fitness cost of all phage resistant clones was broad in terms of growth rate and resistance to grazing by amoeba and could not discriminate K15 capsule to LPS mutants. By contrast, the virulence of the clones tested in mice showed that K15 capsule mutants were as virulent as the wildtype strain while LPS mutants were strongly attenuated. We also found that resistance to one phage led to the sensitization to other phages. In clinics, to control phage-resistant clones that remains virulent phage cocktail should include phages infecting both phage susceptible and future phage resistant clones. ImportanceEscherichia coli is a leading cause of life-threatening infections, including pneumonia acquired during ventilatory assistance for patients hospitalized in Intensive Care Unit, and a major multidrug resistant pathogen. A century-old concept, phage therapy (i.e. using specific anti-bacterial viruses), is being clinically re-evaluated supported with hundreds of successful compassionate phage treatments. However, along billions of years of coevolution bacteria have developed many ways to resist to phages. Phage resistance occurring during phage therapy remains often overlooked despite its critical role for a successful outcome. During this work we characterized phage resistant mutants in a virulent extra-intestinal pathogenic E coli strain and found that (1) phage resistance taking place during a phage treatment in vivo could be predicted from an in vitro assay; (2) phage resistance has, often but not always, a major fitness cost in terms of virulence; and (3) could be countered by appropriate cocktails of phages.

microbiology↗

bioRxiv2021

Evolving social behaviour through selection of single-cell adhesion in Dictyostelium discoideum

The social amoeba Dictyostelium discoideum commonly forms chimeric fruiting bodies. Genetic variants that produce a higher proportion of spores are predicted to undercut multicellular organization unless cooperators assort positively. Cell adhesion is considered a primary factor driving such assortment, but evolution of adhesion has not been experimentally connected to changes in social performance. We modified by experimental evolution the efficiency of individual cells in attaching to a surface. Surprisingly, evolution appears to have produced social cooperators irrespective of whether stronger or weaker adhesion was selected. Quantification of reproductive success, cell-cell adhesion and developmental patterns, however, revealed two distinct social behaviours, as captured when the classical metric for social success is generalized by considering clonal spore production. Our work shows that cell mechanical interactions can constrain evolution of development and sociality in chimeras, and that elucidation of proximate mechanisms is necessary in order to understand the ultimate emergence of multicellular organization.

evolutionary biology↗