Biology subjects

Dubois, P.

Publications and source records attributed to Dubois, P..

4 recordsLinked to original sources

bioRxiv2025

Morphogenesis of the diamond-type stereom microlattice and the origin of saddle-shaped minimal surfaces in the echinoderm skeleton

Echinoderm endoskeleton has a unique trabecular microstructure, called stereom, which can exhibit highly ordered geometries. A striking example of these geometries is the recently discovered "diamond-type" stereom, characterized by a diamond triply periodic minimal surface (D-TPMS) and distinguished by exceptional mechanical and structural properties. Despite its promise for engineering applications, the morphogenesis of this microarchitecture remains poorly understood. Here, we applied a multimodal imaging and labeling approach to investigate the developmental processes underlying the formation of the diamond-type stereom in adults of a starfish Protoreaster nodosus. We showed that this stereom type develops through two principal marginal growth patterns: trabecular trifurcation, which typically occurs horizontally on flat external plate surfaces, oriented approximately along the crystallographic {111} planes of the D-TPMS; and trabecular bifurcation, which generally occurs along plate edges and between trifurcating zones, aligned with the crystallographic {100} planes of the D-TPMS. Although these growth patterns may proceed at different rates, they are tightly coordinated, producing the coherent D-TPMS microarchitecture. Furthermore, we demonstrated that F-actin cytoskeletal deposition is consistently associated with active biomineralization fronts in both diamond-type and less ordered, galleried stereom. Notably, the formation of lateral bridges between adjacent stereom trabeculae is often preceded by catenoid-like F-actin structures, suggesting a guiding and templating role for the cytoskeleton in building trabecular connectivity and shaping its curvature. Given the recurrence of saddle-like features across stereom types, we hypothesize that minimal-surface geometries may emerge from tension-driven cytoskeletal dynamics acting as physical templates during biomineralization. Our observations underscore the critical involvement of the cytoskeleton in adult echinoderm biomineralization. Statement of SignificanceTriple periodic minimal surfaces (TPMS) are geometrically regular, three-dimensionally repeating surfaces that minimize area by maintaining zero mean curvature. Among them, the diamond-type (D-TPMS) is notable for exceptional mechanical stability, uniform porosity, and low surface area-to-volume ratio. Although TPMS-like microarchitectures occur in nature, D-TPMS structures, with large lattice parameters (>10 {micro}m) are exceedingly rare; one natural example is the stereom of certain echinoderms. Yet the mechanism governing the formation of such ordered microstructures remains unresolved. We applied a multi-modal approach to investigate principles of diamond-type stereom morphogenesis. Our results provide key insight into the growth dynamics of this microarchitecture and highlight the essential role of the cytoskeleton, particularly F-actin, in guiding trabecular connectivity and the emergence of minimal-surface geometry, in both periodic and more irregular stereom types.

zoology↗

bioRxiv2024

A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should aim to elicit broad-protection, provide long-lasting immunity and facilitate equitable access for all populations. In this study, a panel of chimeric, full-length spike antigens were developed that incorporate mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was obtained from a high-yield production process in stable CHO cells with purity of >95%, long-term stability and elicitation of broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced protein vaccine (NVX-CoV2373), CoVEXS5 could boost T cell immunity, as well as neutralising antibodies levels against viruses from three sarbecoviruses clades. The breadth of sarbecovirus cross-reactivity elicited by CoVEXS5 exceeded that observed after boosting with the NVX-CoV2373 vaccine. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.

immunology↗

bioRxiv2023

Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants

With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly protective immune responses. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, characterized, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Designed immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. S2 immunization failed to elicit a neutralizing immune response but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 exhibited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), as well as the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 sera also showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 {degrees}C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.

biophysics↗

bioRxiv2021

Investigating densities of Symbiodiniaceae in two species of Antipatharians (black corals) from Madagascar

Here, we report the first methodological approach to investigate the presence and estimate the density of Symbiodiniaceae cells in corals of the order Antipatharia subclass Hexacorallia, known as black corals. Antipatharians are understudied ecosystem engineers of shallow (<30 m depth), mesophotic (30-150 m) and deep-sea (>200 m) reefs. They provide habitat to a vast number of marine fauna, enhancing and supporting coral reefs biodiversity globally. Nonetheless, little biological and ecological information exists on antipatharians, including the extent at which global change disturbances are threatening these corals. The assumption that they were exempted from threats related to climate change was challenged by findings of high density of dinoflagellates within three antipatharian colonies. Further methodical studies were necessary to investigate the regularity of these findings. An integrated design combining microscopy and molecular techniques was used to investigate the presence and estimate density of Symbiodiniaceae cells within two antipatharians species -Cupressopathes abies and Stichopathes maldivensis -from shallow and mesophotic reefs of SW Madagascar. Symbiodiniaceae-like cells were found within the two species from both shallow and mesophotic reefs, although the overall cell density was very low (0-4 cell mm-3). These findings suggest that high abundance of Symbiodiniaceae is not characteristic of antipatharians, which has relevant implications considering disruptions associated to climate change affecting other corals. However, the high densities of dinoflagellates found in antipatharian colonies exposed to higher light irradiance in other studies should be further examined.

molecular biology↗