Biology subjects

Moulin, C.

Publications and source records attributed to Moulin, C..

15 recordsLinked to original sources

bioRxiv2026

Comparison of the 4-helix bundle domains of perilipin 3 and perilipin 4 identifies features that contribute to lipid droplet binding

The perilipins generally represent the most abundant lipid droplet (LD) surface proteins in mammalian cells and can target LD subpopulations within the same cell. They are characterized by a conserved organization of disordered and folded regions, as well as a number of divergent features, which contribute to differences in perilipin function and LD targeting. Here, we focus on the C-terminal 4-helix bundle (4HB) domain that is present in all perilipins except for PLIN1. Using biochemical and in silico approaches, we show that the 4HB of PLIN3 is a stably folded domain and interacts with lipid surfaces in vitro and with LDs in model cells. The {beta}-subdomain at the bottom of the helical bundle is required for the binding to LDs, but not for the 4HB stability, suggesting that this region may promote direct interaction with the LD surface. In agreement, the 4HB of PLIN4, which does not contain an {beta}- subdomain, does not bind to LDs. Overall, our work shows that small differences in perilipin structural features impact their differential targeting to LDs.

biochemistry↗

bioRxiv2026

Diversity, host-specificity, and environmental drivers of the coral reef eukaryome

Coral reefs are among the most diverse ecosystems on Earth, yet the diversity and structure of their associated microeukaryotic communities remain poorly resolved. We characterized reef-associated eukaryomes across 113 reefs spanning the Pacific Ocean using more than 6,300 samples from corals, seawater, and sediments during the Tara Pacific expedition. We identified [~]121,000 eukaryotic ASVs, revealing one of Earths largest undocumented reservoirs of eukaryotic diversity; over 80% of the recovered diversity was previously undetected in global ocean surveys and fewer than 2% of sequences matched reference databases. Reef habitats supported highly distinct communities, with sediments and seawater harboring 20-40-fold higher richness than corals. Unexpectedly, coral-associated communities across 29 host lineages were consistently dominated by small metazoans, particularly demosponges and maxillopods, identifying these taxa as pervasive and previously unrecognized components of coral eukaryomes alongside Apicomplexa. Across the Pacific, eukaryome composition was strongly structured by environmental gradients, with thermal stress emerging as the primary driver of community turnover. Together, these results identify coral reefs as a globally important reservoir of hidden eukaryotic diversity and reveal the reef eukaryome as a sensitive indicator of ecosystem reorganization under climate change.

systems biology↗

bioRxiv2026

HIDDEN APICOMPLEXAN PARASITE DIVERSITY LINKS CORAL AND PLANKTON MICROBIOMES ACROSS REEF SEASCAPES

Parasitism is one of the most widespread trophic strategies in nature, though its diversity and ecological distribution in marine ecosystems remain poorly characterized. Apicomplexa are a major clade of obligate parasites best known for medically important taxa, yet their diversity and distribution in the ocean is still largely unresolved. Here, we used metabarcoding data from the Tara expeditions to investigate the diversity, distribution, and environmental drivers of Apicomplexa across coral reef ecosystems and adjacent oceanic habitats. By integrating samples spanning planktonic communities, coral tissues, and marine sediments across multiple oceanic regions, we substantially expand the known phylogenetic breadth of marine apicomplexans. Although apicomplexans were generally low in relative abundance, they were widely distributed across marine environments. Community composition differed markedly among habitats. Corallicolid lineages were consistently associated with coral hosts, whereas planktonic samples harbored a greater diversity of apicomplexans, dominated by crustacean-associated gregarines. Sediments contained particularly high apicomplexan richness, including several poorly characterized groups. Capitalizing on the pan-Pacific transect of the expedition, we resolved biogeographic patterns in apicomplexan diversity across ocean basins: tropical regions showed the highest overall diversity, while polar environments contained distinct apicomplexan assemblages not detected in other ocean biomes. Together, these results highlight the extensive and previously underappreciated diversity of marine Apicomplexa and demonstrate that integrating multiple marine biomes is essential for resolving the phylogenetic and ecological breadth of parasitism in the ocean.

genomics↗

bioRxiv2026

Ocean-scale transcriptomic analysis of corallicolids (Apicomplexa) reveals their ubiquity and molecular interactions with Pocillopora corals.

Corals are complex holobionts, encompassing numerous prokaryotes, viruses, and protists. This associated microbial community strongly influences coral health and its resilience to global ocean warming. Corallicolid apicomplexans are widespread coral-infecting parasites, yet their impact on the coral host remains poorly understood. This knowledge gap largely stems from the low abundance of these parasites in coral tissues, which makes them difficult to isolate and access to their genetic material. Here we analyzed nearly 1,000 Pocillopora coral colonies collected from 32 islands during the Tara Pacific expedition to identify the drivers of corallicolid prevalence and abundance. Corallicolids were detected in almost all Pocillopora colonies with variable relative abundances between islands. The high abundance of specific corallicolid populations correlates with seawater temperature and levels of host protein carbonylation. We used a large collection of 297 metatranscriptomes to assemble a corallicolid transcriptome and we identified apicomplexan parasite signature genes, including the GRA9 and PV2 confirming the close phylogenetic relationship with the family of Eimeriidae. Gene expression patterns indicate that the high abundance of corallicolids correlates with a high transcription of genes encoding apical complex proteins and genes involved in the control of host immune defenses. Overall, this study provides new insights into corallicolid biology and its interaction with the coral host by combining a newly generated transcriptome with a large-scale sampling of Pocillopora corals across the Pacific Ocean.

genomics↗

bioRxiv2026

Triglyceride/Cholesterol Ester Ratio Encodes Lipid Droplet Size and Diversity

Lipid droplet (LD) heterogeneity is a hallmark of their pathophysiological relevance. This is especially evident when cells sequester toxic cholesterol by converting it into cholesterol esters (CEs) within LDs. Since CEs can form liquid crystals (LCs), it remains unclear how such ordered structures are accommodated within the inherently dynamic environment of LDs. Here, we show that the fluidizing properties of triglycerides (TGs) help CE incorporation and influence LD growth and heterogeneity. Seipin, the key regulator of TG-LD formation and size, does not significantly impact CE-rich LD size. Instead, the CE/TG ratio, the sequence of neutral lipid deposition, and the activity of diacylglycerol acyltransferases, especially DGAT2, determine whether LDs enlarge, remain fluid, or lock into LC phases. We found that the LC phase resists LD ripening and acts as a kinetic barrier to lipid entry. Lastly, we observe that perilipins, the most abundant LD surface proteins, differentially target CE-rich LDs: Plin3 and 5 are excluded from them, whereas Plin2 and 4 are favored. These findings highlight the CE/TG ratio as a key organizing principle of lipid storage and LD function, with immediate relevance for diseases linked to sterol accumulation.

cell biology↗

bioRxiv2025

Perilipin 4 repetitive region forms amyloid fibrils promoted by a genetic expansion found in myopathy patients

Lipid-binding amphipathic proteins play key roles in cellular organization, yet their conformational flexibility makes them prone to aggregation. Here we study the aggregation of perilipin 4 (PLIN4), a protein of the lipid droplet (LD)-binding perilipin family. PLIN4 contains an unusually long ([~]1000 amino acid, aa) amphipathic helix composed of tandem 33-aa repeats, which folds on the LD surface. A genetic expansion that increases the number of repeats is associated with skeletal muscle dysfunction in patients suffering from a late-onset vacuolar myopathy (MRUPAV). We show that the genetic expansion and the precise sequence of the 33 aa repeats do not significantly alter PLIN4 interaction with LDs in cells. By contrast, purified fragments of the PLIN4 repetitive region form amyloid fibrils as characterized by cryo-EM and atomic force microscopy. Repeat expansion strongly accelerates fibril formation, consistent with enhanced self-assembly driven by the accumulation of identical repeats. PLIN4 aggregation is attenuated by the presence of LDs, indicating that lipid binding modulates the balance between membrane association and self-assembly. Together, these results establish PLIN4 as a previously unrecognized amyloid-forming protein and suggest that repeat expansion enhances amyloidogenic self-assembly, providing a foundation for future studies of its role in degenerative muscle disease.

biochemistry↗

bioRxiv2024

Genome-resolved diversity and biosynthetic potential of the coral reef microbiome

Coral reefs are marine biodiversity hotspots that provide a wide range of ecosystem services. They are also reservoirs of bioactive compounds, many of which are produced by microbial symbionts associated with reef invertebrate hosts. However, for the keystone species of coral reefs--the reef-building corals themselves--we still lack a systematic assessment of their microbially encoded biosynthetic potential, and thus the molecular resources that may be at stake due to the alarming decline in reef biodiversity and cover. Here, we analysed microbial genomes reconstructed from 820 reef-building coral samples of three representative coral genera collected at 99 reefs across 32 islands during a two-year expedition throughout the Pacific Ocean (Tara Pacific). By contextualising our analyses with the microbiomes of other reef species, we found that genomic information was previously available for only 10% of the 4,224 microbial species overall and for less than 1% of the 645 species exclusively identified in Tara Pacific samples. We found reef-building coral microbiomes to be host-specific and their biosynthetic potential to rival or even surpass that found in traditional targets for natural product discovery, such as sponges and soft corals. Fire corals were not only particularly diverse in microbially encoded biosynthetic gene clusters (BGCs), but also in BGC-rich bacteria, including Acidobacteriota spp., which have been recently highlighted for their promising natural product repertoire. Together, this study unveils new candidate sources for bioactive compound discovery, prioritises targets for microbial isolation, and underscores the importance of conservation efforts by linking macro-organismal biodiversity loss to host-specific microbiomes and their biotechnological potential.

microbiology↗

bioRxiv2024

Genetic ablation of the DNA demethylation pathway in retinal progenitor cells impairs photoreceptor development and function, leading to retinal dystrophy

Rod and cone photoreceptors are critical for vision, and their loss leads to blindness. Photoreceptors are epigenetically unique, because the promoters of the genes required for the development and function of these neurons are hypermethylated in retinal progenitor cells (RPCs) and hypomethylated in photoreceptors. However, the mechanism responsible for DNA demethylation during the differentiation of RPCs into photoreceptors and its role in photoreceptor development and function were unknown. We hypothesized that the Ten-Eleven Translocation (TET) family of dioxygenases plays a key role in this mechanism. To this end, we knocked out all TET genes in RPCs and characterized the TET-deficient and control retinas using various approaches including electron microscopy, electroretinogram (ERG) tests, RNA-seq, whole genome bisulfite sequencing (WGBS), and 5hmC-Seal. We found that genetic ablation of the TET family prevents demethylation of the promoters of genes essential for rod specification and for rod and cone maturation during the differentiation of RPCs into photoreceptors. Preservation of methylated cytosines in the promoters of these genes significantly reduced their expression, which was confirmed by western blot analysis. This impaired expression leads to the underdevelopment or complete absence of outer segments and synaptic termini in the photoreceptors of TET-deficient retinas, which results in loss of rod and cone function, as assayed by ERG. These function-deprived, underdeveloped photoreceptors die over time, which leads to blindness.

neuroscience↗

bioRxiv2024

Plasma cell heterogeneity is driven by type of immune challenge

Plasma cells play an essential role in humoral immunity, but many questions remain regarding the heterogeneity of this population, both in terms of ontogeny and involvement in the immune response. In this work, we have identified 5 subsets of plasma cells in human and mouse lymphoid tissues. These subpopulations were distinguished by differential expression of CD62L, CXCR4, Fc{gamma}RIIb and CD93. The antigenic context as well as the B cell of origin directed plasma cell differentiation towards specific subtypes that display distinct migratory and survival abilities in vivo. Altogether, ours results unveil that plasma cell phenotypic and functional heterogeneity relies on intrinsic imprinting during B cell activation.

immunology↗

bioRxiv2023

CXCR4 signaling strength regulates hematopoietic multipotent progenitor fate through extrinsic and intrinsic mechanisms

How cell-extrinsic niche-related and cell-intrinsic cues drive lineage specification of hematopoietic multipotent progenitors (MPPs) in the bone marrow (BM) is partly understood. We show that CXCR4 signaling strength regulates localization and fate of MPPs. In mice phenocopying the BM myeloid skewing of patients with WHIM Syndrome (WS), a rare immunodeficiency caused by gain-of-function CXCR4 mutations, enhanced mTOR signaling and overactive Oxphos metabolism were associated with myeloid rewiring of lymphoid-primed MPPs (or MPP4). Fate decision of MPP4 was also affected by molecular changes established at the MPP1 level. Mutant MPP4 displayed altered BM localization relative to peri-arteriolar structures, suggesting that extrinsic cues contribute to their myeloid skewing. Chronic treatment with CXCR4 antagonist AMD3100 or mTOR inhibitor Rapamycin rescued lymphoid capacities of mutant MPP4, demonstrating a pivotal role for the CXCR4-mTOR axis in regulating MPP4 fate. Our study thus provides mechanistic insights into how CXCR4 signaling regulates the lymphoid potential of MPPs.

cell biology↗

bioRxiv2022

From genome wide SNPs to genomic islands of differentiation: the quest for species diagnostic markers in two scleractinian corals, Pocillopora and Porites

Coral reefs are of paramount importance in marine ecosystems, where they provide support for a large part of the biodiversity. Being quite sensitive to global changes, they are therefore the prime targets for biodiversity conservation policies. However, such conservation goals require accurate species identification, which are notoriously difficult to get in these highly morphologically variable organisms, rich in cryptic species. There is an acute need for easy-to-use and resolutive species diagnostic molecular markers. The present study builds on the huge sequencing effort developed during the TARA Pacific expedition to develop a genotyping strategy to assign coral samples to the correct species within two coral genera (Porites and Pocillopora). For this purpose, we developed a technique that we called "Divergent Fragment" based on the sequencing of a less than 2kb long diagnostic genomic fragment determined from the metagenomic data of a subset of the corals collected. This method has proven to be rapid, resolvable and cost-effective. Sequencing of PCR fragments nested along the species diagnostic fragment allowed us to assign 232 individuals of the genus Pocillopora and 247 individuals of the genus Porites to previously identified independent genetic lineages (i.e. species). This genotyping method will allow to fully analyze the coral samples collected across the Pacific during the Tara Pacific expedition and opens technological perspectives in the field of population genomics-guided conservation.

evolutionary biology↗

bioRxiv2022

Disparate patterns of genetic divergence in three widespread corals across a pan-Pacific environmental gradient highlights species-specific adaptation trajectories.

Tropical coral reefs are among the worst affected ecosystems by climate change with predictions ranging between a 70-90% loss of reefs in the coming decades. Effective conservation strategies that maximize ecosystem resilience, and potential for recovery, must be informed by the accurate characterization of extant genetic diversity and population structure together with an understanding of the adaptive potential of keystone species. Here, we analyzed samples from the Tara Pacific Expedition (2016 to 2018) that completed an 18,000 km longitudinal transect of the Pacific Ocean sampling three widespread corals - Pocillopora meandrina, Porites lobata, and Millepora cf. platyphylla - across 33 sites from 11 islands. Using deep metagenomic sequencing of 269 colonies in conjunction with morphological analyses and climate variability data we can show that the sampled transect encompasses multiple morphologically cryptic species that exhibit disparate biogeographic patterns, and most importantly, distinct evolutionary patterns, despite exposure to identical environmental regimes. Our findings demonstrate on a basin-scale that evolutionary trajectories are species-specific and complex, and can only in part be predicted from the environment. This highlights that conservation strategies must integrate multi-species investigations to consider the distinct genomic footprints shaped by selection as well as the genetic potential for adaptive change.

genetics↗

bioRxiv2022

Open science resources from the Tara Pacific expedition across coral reef and surface ocean ecosystems

AbstractThe Tara Pacific expedition (2016-2018) sampled coral ecosystems around 32 islands in the Pacific Ocean and the ocean surface waters at 249 locations, resulting in the collection of nearly 58,000 samples. The expedition was designed to systematically study warm coral reefs and included the collection of corals, fish, plankton, and seawater samples for advanced biogeochemical, molecular, and imaging analysis. Here we provide a complete description of the sampling methodology, and we explain how to explore and access the different datasets generated by the expedition. Environmental context data were obtained from taxonomic registries, gazetteers, almanacs, climatologies, operational biogeochemical models, and satellite observations. The quality of the different environmental measures has been validated not only by various quality control steps but also through a global analysis allowing the comparison with known environmental large-scale structures. Such a wide released datasets opens the perspective to address a wide range of scientific questions.

ecology↗

bioRxiv2022

Pervasive gene duplications as a major evolutionary driver of coral biology

Over the last decade, several coral genomes have been sequenced allowing a better understanding of these symbiotic organisms threatened by climate change. Scleractinian corals are reef builders and are central to these ecosystems, providing habitat and food to a great diversity of species. In the frame of the Tara Pacific expedition, we generated two coral genomes, Porites lobata and Pocillopora meandrina with vastly improved contiguity that allowed us to study the functional organisation of these genomes. We annotated their gene catalog and report a relatively higher gene number (43,000 and 32,000 genes respectively) than that found in other public coral genome sequences. This finding is explained by a high number of tandemly duplicated genes (almost a third of the predicted genes). We show that these duplicated genes originate from multiple and distinct duplication events throughout the coral lineage. They contribute to the amplification of gene families, mostly related to immune system and disease-resistance, which we suggest to be functionally linked to coral host resilience. At large, we show the importance of duplicated genes to inform the biology of reef-building corals and provide novel avenues to understand and screen for differences in stress resilience.

genomics↗

bioRxiv2020

Outer membrane lipoprotein DolP interacts with the BAM complex and promotes fitness during envelope stress response

In Gram-negative bacteria, coordinated remodelling of the outer membrane (OM) and the peptidoglycan is crucial for envelope integrity. Envelope stress caused by unfolded OM proteins (OMPs) activates sigmaE ({sigma}E) in Enterobacteria. {sigma}E upregulates OMP biogenesis factors, including the {beta}-barrel assembly machinery (BAM) that catalyzes OMP-folding. Elevated {sigma}E activity, however, can be detrimental for OM integrity. Here we report that DolP (YraP), a {sigma}E-upregulated OM lipoprotein important for envelope integrity, is a novel interactor of BAM and we demonstrate that OM-assembled BamA is a critical determinant of the BAM-DolP complex. Mid-cell recruitment of DolP had been previously associated to activation of septal peptidoglycan remodelling during cell division, but its role during envelope stress was unknown. We now show that DolP promotes cell fitness upon stress-induced activation of {sigma}E and opposes a detrimental effect caused by the overaccumulation of BAM in the OM. During envelope stress, DolP loses its association with the mid-cell, thus suggesting a possible link between envelope stress caused by impaired OMP biogenesis and the regulation of a late step of cell division.

microbiology↗