Biology subjects

Gibson, M.

Publications and source records attributed to Gibson, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease

Single-cell studies have defined immune states in inflammatory bowel disease (IBD), but how adaptive receptor histories organize circulating immunity remains unclear. We generated a single-cell transcriptomic atlas of peripheral blood from 249 participants with Crohn's disease, ulcerative colitis, or non-IBD control status, including 182 with productive TCR and BCR recovery. Expanded TCR clonotypes marked inflammatory-memory and cytotoxic states, while distinct but similar paired TCRs shared inflammatory programs across participants. BCR lineage maturation linked IgA-associated mucosal and plasma B cell programs to somatic mutation and class switching, distinguishing maturation-associated biology from clonal expansion. Helper, regulatory, and cytotoxic T-cell programs covaried with B-cell states, and inferred interactions nominated reciprocal antigen-presentation and helper pathways. Repertoire-based machine learning distinguished diagnosis, inflammation, and contemporaneous six-month treatment-response status. Together, this atlas connects receptor architecture to coordinated systemic immune remodeling, establishes a foundation for repertoire-informed patient stratification, and prioritizes candidate mechanisms of IBD pathogenesis.

immunology↗

bioRxiv2026

Genomic history and selection in Roman and early medieval Britain

Leading biomedical resources rely on genome variation in Britain1-3, but the historical processes that shaped present-day fine-scale diversity remain debated4-13. Here we sequenced 1039 ancient shotgun genomes from Britain (median 1.4-fold coverage), primarily dating to the first millennium CE. We imputed [~]660 million variants in the UK Biobank14-16 and employed genealogy-based ancestry reconstruction. We found an association between Iron Age consanguinity and matrilineal burial practices17, later disrupted following the Roman Conquest. Despite this societal impact, only 20% of Roman-period individuals carried detectable ancestry from outside Britain. In contrast, from the 6th century CE we detect widespread influx of ancestry in over 70% of individuals in southernAnglo-Saxon Britain, with limited local admixture. We find previously underappreciated heterogeneity, with ancestries associated with Central and Southern Europe rising in prevalence from the 7th century CE. We demonstrate distinct Scandinavian-related ancestry in many Viking-associated contexts, but show that the population-level impact of the Viking Age in Britain was limited. Finally, we detect pre-medieval selection on variants linked with key immunity genes TLR10-TLR1 and IRF8. These results identify population-level and selective processes that shape variation and disease risk in Britain today.

genomics↗

bioRxiv2025

A comprehensive bulk and single-cell transcriptional atlas of pediatric leukemias

Advancements in understanding the molecular factors driving pediatric leukemias have led to an ever-increasing volume and diversity of data being generated. Recent studies are moving beyond DNA-based profiling to incorporate transcriptional data, enhancing the characterization of these cancers and informing clinical decisions. However, many existing datasets focus on specific leukemia subtypes, limiting the extraction of broader clinically relevant insights. Here, we present a comprehensive dataset of bulk and single-cell transcriptional data from 69 pediatric leukemia patients, encompassing eight leukemias. This is one of the most diverse pediatric leukemia datasets published to date. Through comparative analysis and explainable machine learning, we demonstrate the utility of these datasets in improving pediatric leukemia characterization and supporting the integration of transcriptional data into clinical testing.

cancer biology↗

bioRxiv2025

The ecology and adaptive function of clownfish color patterns

Anti-predator coloration strategies vary widely from conspicuous to cryptic, and everything between. Coloration serves multiple functions, and determining the selective pressures that drive this diversity is a long-standing mystery. Clownfishes display enormous inter- and intra-specific variation in coloration without the influence of sexual selection, providing an excellent system in which to explore these drivers in closely related and sympatric species. Across clownfishes, three color-pattern phenotypes have evolved convergently with host anemone use, implying adaptive functions linked to the hosts physical and chemical properties. Here we conducted a comprehensive study to infer the ultimate functions of clownfish color patterns. By integrating multiple levels of biological organization, including behavior, visual ecology, dietary niche, and microbiome, our data overwhelmingly indicate that specialist and generalist clownfish color patterns have different underlying ecologies and adaptive functions. Specialist clownfishes background match their anemones, remain near hosts, and have specialized diets and microbiomes. Generalists are highly contrasting with their anemones, remain far from hosts, and have variable diets and microbiomes. Taken together, specialist color patterns align with functional expectations of camouflage while generalists align with aposematic or disruptive coloration. Our study provides novel insights into how ecological conditions shape the evolution of multiple anti-predator coloration strategies.

ecology↗

bioRxiv2025

FAVABEAN and FALAPhyl: Open-Source Pipelines for Scalable 16s rRNA Microbiome Data Processing and Visualization

Reproducible and scalable analysis of 16S rRNA amplicon sequencing data remains a persistent challenge in microbiome research due to the complexity of available tools, incompatibilities between platforms, and the need for extensive bioinformatics expertise. We developed two containerized workflows--FAVABEAN (Fast Amplicon Variant Annotation, Binning, Error-correction And ANalysis) and FALAPhyl (Forays into Automating Laborious Analyses of Phylogeny)--to address these challenges. FAVABEAN and FALAPhyl are Snakemake-based pipelines designed for flexible execution across local, cluster, and cloud environments. FAVABEAN automates preprocessing, ASV inference, and taxonomic assignment using DADA2 and FIGARO, including primer averaging when samples are sequenced with multiple primers. FALAPhyl supports downstream analysis including alpha/beta diversity, network analysis, and differential abundance testing, with integrated provenance tracking. We validated both pipelines using three case studies involving oral microbiome datasets. In Case Study 1, we compared oral microbiota across family members and niches, showing primer-dependent variability in ASV-based similarity and minimal reseeding from familial sources after prophylaxis. Case Study 2 analyzed dental aerosol samples, revealing no significant microbial differences between pre-, intra-, and post-procedure air. Case Study 3, a randomized trial of a nitrate mouthrinse, demonstrated no significant microbiome shifts, highlighting oral microbial stability. FALAPhyls integration of DAtest enabled empirical evaluation of multiple statistical tests, aiding robust differential abundance inference. FAVABEAN and FALAPhyl offer a reproducible, automated solution for 16S rRNA amplicon data analysis. Their modular design, containerization, and provenance tracking enhance accessibility and scientific rigor in microbiome research.

bioinformatics↗

bioRxiv2025

Substituent-based Modulation of Self-Assembly and Immunogenicity of Amphipathic Peptides

Peptide-based biomaterials assembled through monomer-by-monomer self-assembly provide versatile platforms for biomedical applications due to their adjustable physicochemical properties, biocompatibility, and dynamic nature. The self-assembly process largely depends on primary sequence features, such as hydrophobicity, length, and charge, which influence the formation of various nanostructures, including fibrils and hydrogels. Amphipathic peptides, characterized by alternating polar and hydrophobic residues, are especially effective in forming supramolecular nanofibers stabilized by {pi}-{pi} interactions and hydrogen bonds. Chemical modifications, particularly on aromatic side chains, have proven to be a promising approach for controlling assembly morphology, stability, and biological activity. In organic chemistry, the use of chemical substituents, such as halogens, alkyl groups, or electron-donating and electron-withdrawing groups, has been widely employed to alter reactivity, stability, and molecular interactions for diverse applications, including catalysts, pharmaceuticals, and materials science. However, the influence of these substituents on peptide packing and in vivo immunogenicity remains relatively unexplored. In this study, we systematically examine how changes in the position and nature of substituents on benzyl groups attached to short amphipathic peptides affect self-assembly, fibril morphology, and immune responses. By introducing different electron-donating and withdrawing groups at the para-position of benzyl rings and modifying the chain length connecting the backbone to the aromatic moiety, we observe notable effects on fibril formation, molecular packing, and immunogenicity both in vitro and in vivo. Our results show that subtle chemical modifications are effective tools for designing tailored peptide nanomaterials with promising potential in vaccine delivery, tissue engineering, and regenerative medicine.

bioengineering↗

bioRxiv2025

Using evolution as a tool: Replacing corolla in Drosophila melanogaster with its Drosophila mauritiana ortholog creates a novel hypomorphic allele

In Drosophila melanogaster females, as in most organisms, the segregation of meiotic chromosomes depends on the proper distribution of crossovers along paired maternal and paternal chromosomes. In most cases, crossovers require the synaptonemal complex (SC), a conserved multi-protein structure that forms between homologous chromosomes in meiotic prophase I. Recent studies leveraging hypomorphic alleles suggest that the SC plays a more direct role in the distribution of crossover events. However, identifying additional hypomorphic mutations that avoid catastrophic phenotypes by partially disrupting the SC has been challenging. Here, to create a new hypomorphic allele of the D. melanogaster SC gene corolla, we used CRISPR/Cas9 to replace it with the coding sequence of its Drosophila mauritiana ortholog, yielding corollamau. Since the amino acid sequence of SC proteins is rapidly diverging while maintaining the general tripartite structure of the SC, we hypothesized that this replacement would enable the assembly of the SC but show defects in crossover distribution. Indeed, at 25 {degrees}C corollamau homozygous females exhibited full-length SC with defects in SC maintenance and crossover formation, resulting in moderate levels of chromosome missegregation. At 18 {degrees}C, SC maintenance was rescued, and recombination rates were improved, although they remained significantly lower than observed in wild type. Importantly, these phenotypes are less severe than observed in corolla null mutant flies, suggesting corollamau is a hypomorphic allele. Unexpectedly, in homozygotes we also observed unique polycomplexes composed of the SC proteins Corolla and Corona but lacking the transverse filament protein C(3)G. Overall, we report a novel hypomorphic allele of corolla that will enable future studies on the role of the SC in crossover distribution. Further, the unique polycomplexes found in mutant flies may provide new insights into SC protein-protein interactions and SC architecture. Author SummaryIn many species, the success of sexual reproduction relies on a protein structure called the synaptonemal complex (SC). The SC forms between the maternal and paternal copies of chromosomes and functions to ensure crossing over. Most prior studies have used SC mutants that have grave defects, preventing the study of nuances in SC function. Here, we replace one of the SC genes in Drosophila melanogaster with the ortholog of a close relative, creating a new allele that displays a partial loss-of-function phenotype. At the standard rearing temperature, flies homozygous for this allele exhibit SC maintenance defects, a reduced number of crossover events, and aberrant chromosome segregation. In flies reared at a lower temperature, SC maintenance is rescued but the defects in recombination and chromosome segregation persist. We also found a unique SC protein aggregate in these flies. Altogether, this new mutant reflects a novel approach to study the structure and function of the SC.

genetics↗

bioRxiv2025

A typology of Australian terrestrial bird communities

AimIncreasing interest in holistic measurement of the response of fauna communities to interventions requires suitable community condition metrics. However, the development of such metrics is hindered by the absence of broad-scale typologies at suitable spatial and ecological resolutions. We aimed to derive a preliminary typology of terrestrial bird communities for Australia, based on bird co-occurrence data, and describe and map the likely distribution of each community type across the continent. LocationMainland Australia, continental islands Time period1973-2022 Major taxa studiedAves MethodsWe used fine-scale co-occurrence data from standard 2-ha surveys in BirdLife Australias citizen-science database. After filtering to reduce bias, we used hierarchical clustering followed by iterative consultation with experts to identify reliably distinct and recognisable terrestrial bird communities across Australia. We used Maxent to model the likely distributions of each community, and developed community descriptions based on each communitys composition and distribution. ResultsThe resultant typology included 29 reliably distinct and recognisable bird communities with major clusters corresponding with seven broad geographical regions. The distributions of bird communities did not correspond tightly to the boundaries of major vegetation groups, with most communities occurring across multiple vegetation types. Main ConclusionsOur preliminary typology of bird communities provides a standard classification at a continental scale. It newly defines distinct bird communities as entities for which condition benchmarks can be established to allow assessment of their conservation status and monitoring of change over time. Refinement will enable cryptic communities in areas with sparse data to be identified. The method could be translated to other regions where adequate coverage of data in the form of standardised surveys of fauna are available. Vast biodiversity datasets delivered through citizen science programs provide the opportunity to develop such typologies for fauna communities, as a precursor to developing targeted and informative community condition metrics.

ecology↗

bioRxiv2024

A new spin on chemotaxonomy using non-proteogenic amino acids as a test case

PremiseSpecialized metabolites serve various roles for plants and humans. Unlike core metabolites, specialized metabolites are restricted to certain lineages. Thus, in addition to their ecological functions, specialized metabolites can serve as diagnostic markers of plant lineages. MethodsWe investigate the phylogenetic distribution of plant metabolites using non-proteogenic amino acids (NPAA). Species-NPAA associations for eight NPAAs were identified from the existing literature and placed within a phylogenetic context using R packages and interactive tree of life. To confirm and extend the literature-based NPAA distribution we selected azetidine-2-carboxylic acid (Aze) and screened over 70 diverse plants using GC-MS. ResultsLiterature searches identified > 900 NPAA-relevant articles, which were manually inspected to identify 560 species-NPAA associations. NPAAs were mapped at the order and genus level, revealing that some NPAAs are restricted to single orders, whereas others are present across divergent taxa. The distribution of Aze across plants suggests a convergent evolutionary history. DiscussionThe reliance on chemotaxonomy has decreased over the years. Yet, there is still value in placing metabolites within a phylogenetic context to understand the evolutionary processes of plant chemical diversification. This approach can be applied to metabolites present in any organism and compared at a range of taxonomic levels.

plant biology↗

bioRxiv2024

An evolutionarily conserved Hox-Gbx segmentation code in the rice coral Montipora capitata

Segmentation of the gastric cavity is a synapomorphic trait of cnidarians of the class Anthozoa (corals and sea anemones), with different clades forming distinct numbers of segments. In the starlet sea anemone Nematostella vectensis, for example, eight bilaterally positioned gastric segments are generated by the action of a group of Hox-Gbx genes in the developing larval endo-mesoderm. Still, given the range of segment numbers observed in different anthozoans, it remains unclear whether this Hox-Gbx module is evolutionarily conserved and how it might be deployed to generate different numbers of segments. Here, we systematically interrogate the role of Hox-Gbx genes during development of the rice coral Montipora capitata. We first characterize the temporal sequence of segmentation in M. capitata juveniles and then combine transcriptomic profiling and in situ hybridization to identify three conserved homeobox-containing genes, McAnthox8, McAnthox6a.1 and McGbx, which are collectively expressed in the developing endo-mesoderm prior to and during segment formation. The expression boundaries of these genes prefigure the positions of the first six segment boundaries, similar to their Nematostella homologs. Further, we show that chemical inhibition of BMP activity at the planula stage abolishes the expression of Hox-Gbx genes, leading to the formation of an unsegmented gastric cavity. These findings demonstrate the existence of a functionally conserved Hox-Gbx module in evolutionarily divergent anthozoan species, suggesting that the last common ancestor of all anthozoans likely utilized a similar genetic toolkit to axially pattern the endo-mesoderm into metameric subunits.

evolutionary biology↗

bioRxiv2024

Patient-derived colon epithelial organoids reveal lipid-related metabolic dysfunction in pediatric ulcerative colitis

Background & AimsUlcerative colitis (UC) is associated with epithelial metabolic derangements which exacerbate gut inflammation. Patient-derived organoids recapitulate complexities of the parent tissue in health and disease; however, whether colon organoids (colonoids) model metabolic impairments in the pediatric UC epithelium is unclear. This study determined the functional metabolic differences in the colon epithelia using epithelial colonoids from pediatric patients. MethodsWe developed biopsy-derived colonoids from pediatric patients with endoscopically active UC, inactive UC, and those without endoscopic or histologic evidence of colon inflammation (non-IBD controls). We extensively interrogated metabolic dysregulation through extracellular flux analyses and tested potential therapies that recapitulate or ameliorate such metabolic dysfunction. ResultsEpithelial colonoids from active UC patients exhibit elevated oxygen consumption and proton leak supported by enhanced glycolytic capacity and dysregulated lipid metabolism. The hypermetabolic features in active UC colonoids were associated with increased cellular stress and chemokine secretion, specifically during differentiation. Transcriptomic and pathway analyses indicated a role for PPAR- in lipid-induced hypermetabolism in active UC colonoids, which was validated by PPAR- activation in non-IBD colonoids. Accordingly, limiting neutral lipid accumulation in active UC colonoids through pharmacological inhibition of PPAR- induced a metabolic shift towards glucose consumption, suppressed hypermetabolism and chemokine secretion, and improved cellular stress markers. Control and inactive UC colonoids had similar metabolic and transcriptomic profiles. ConclusionsOur pediatric colonoids revealed significant lipid-related metabolic dysregulation in the pediatric UC epithelium that may be alleviated by PPAR- inhibition. This study supports the advancement of colonoids as a preclinical human model for testing epithelial-directed therapies against such metabolic dysfunction. What You Need to KnowO_ST_ABSBackground and ContextC_ST_ABSColon mucosa healing in pediatric UC requires reinstating normal epithelial function but a lack of human preclinical models of the diseased epithelium hinders the development of epithelial-directed interventions. New FindingsUsing colon biopsy-derived epithelial organoids, samples from pediatric patients with active UC show hyperactive metabolic function largely driven by enhanced lipid metabolism. Pharmacologic inhibition of lipid metabolism alleviates metabolic dysfunction, cellular stress, and chemokine production. LimitationsThough our epithelial colon organoids from active UC patients show targetable metabolic and molecular features from non-IBD controls, they were cultured under sterile conditions, which may not fully capture any potential real-time contributions of the complex inflammatory milieu typically present in the disease. Clinical Research RelevanceCurrent therapies for pediatric UC mainly target the immune system despite the need for epithelial healing to sustain remission. We identified a pharmacologic target that regulates epithelial metabolism and can be developed for epithelial-directed therapy in UC. Basic Research RelevancePediatric UC patient tissue adult stem cell-derived colon epithelial organoids retain disease-associated metabolic pathology and can serve as preclinical human models of disease. Excess reliance on lipids as an energy source leads to oxidative and inflammatory dysfunction in pediatric UC colon organoids. Preprint: This manuscript is currently on bioRxiv. doi: https://doi.org/10.1101/2024.08.22.609271 Lay Summary: Using patient tissue-derived colon epithelial organoids, the investigators identified epithelial metabolic dysfunction and inflammation in pediatric ulcerative colitis that can be alleviated by PPAR-a inhibition.

physiology↗

bioRxiv2024

DeepSomatic: Accurate somatic small variant discovery for multiple sequencing technologies

Somatic variant detection is an integral part of cancer genomics analysis. While most methods have focused on short-read sequencing, long-read technologies now offer potential advantages in terms of repeat mapping and variant phasing. We present DeepSomatic, a deep learning method for detecting somatic SNVs and insertions and deletions (indels) from both short-read and long-read data, with modes for whole-genome and exome sequencing, and able to run on tumor-normal, tumor-only, and with FFPE-prepared samples. To help address the dearth of publicly available training and benchmarking data for somatic variant detection, we generated and make openly available a dataset of five matched tumor-normal cell line pairs sequenced with Illumina, PacBio HiFi, and Oxford Nanopore Technologies, along with benchmark variant sets. Across samples and technologies (short-read and long-read), DeepSomatic consistently outperforms existing callers, particularly for indels.

bioinformatics↗

bioRxiv2023

Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma

Background/AimsEosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown. MethodsEosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient ({Delta}dblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (Ccl11-/-). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils. ResultsActivated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models (Ccl11-/- mice, {Delta}dblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer. In vitro co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. {Delta}dblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways. ConclusionEosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.

cancer biology↗

bioRxiv2023

Spatial transcriptomics reveals a conserved segment polarity program that governs muscle patterning in Nematostella vectensis

During early animal evolution, the emergence of axially-polarized segments was central to the diversification of complex bilaterian body plans. Nevertheless, precisely how and when segment polarity pathways arose remains obscure. Here we demonstrate the molecular basis for segment polarization in developing larvae of the pre-bilaterian sea anemone Nematostella vectensis. Utilizing spatial transcriptomics, we first constructed a 3-D gene expression atlas of developing larval segments. Capitalizing on accurate in silico predictions, we identified Lbx and Uncx, conserved homeodomain-containing genes that occupy opposing subsegmental domains under the control of both BMP signaling and the Hox-Gbx cascade. Functionally, Lbx mutagenesis eliminated all molecular evidence of segment polarization at larval stage and caused an aberrant mirror-symmetric pattern of retractor muscles in primary polyps. These results demonstrate the molecular basis for segment polarity in a pre-bilaterian animal, suggesting that polarized metameric structures were present in the Cnidaria-Bilateria common ancestor over 600 million years ago. HighlightsO_LINematostella endomesodermal tissue forms metameric segments and displays a transcriptomic profile similar to that observed in bilaterian mesoderm C_LIO_LIConstruction of a comprehensive 3-D gene expression atlas enables systematic dissection of segmental identity in endomesoderm C_LIO_LILbx and Uncx, two conserved homeobox-containing genes, establish segment polarity in Nematostella C_LIO_LIThe Cnidarian-Bilaterian common ancestor likely possessed the genetic toolkit to generate polarized metameric structures C_LI

evolutionary biology↗

bioRxiv2022

Neonatal hyperoxia induces sex-dependent pulmonary cellular and transcriptomic changes in an experimental mouse model of bronchopulmonary dysplasia

Hyperoxia (HOX) disrupts lung development in mice and causes bronchopulmonary dysplasia (BPD) in neonates. To investigate sex-dependent molecular and cellular programming involved in HOX, we surveyed the mouse lung using single cell RNA sequencing (scRNA-seq), and validated our findings in human neonatal lung cells in vitro. HOX-induced inflammation in alveolar type (AT) 2 cells gave rise to damage associated transient progenitors (DATP). It also induced a new subpopulation of AT1 cells with reduced expression of growth factors normally secreted by AT1 cells, but increased mitochondrial gene expression. Female alveolar epithelial cells had less EMT and pulmonary fibrosis signaling in HOX. In the endothelium, expansion of Car4+ EC (Cap2) was seen in HOX along with an emergent subpopulation of Cap2 with repressed VEGF signaling. This regenerative response was increased in females exposed to HOX. Mesenchymal cells had inflammatory signatures in HOX, with a new distal interstitial fibroblast subcluster characterized by repressed lipid biosynthesis and a transcriptomic signature resembling myofibroblasts. HOX-induced gene expression signatures in human neonatal fibroblasts and alveolar epithelial cells in vitro resembled mouse scRNA-seq data. These findings suggest that neonatal exposure to HOX programs distinct sex-specific stem cell progenitor and cellular reparative responses that underpin lung remodeling in BPD.

developmental biology↗

bioRxiv2021

The architecture and operating mechanism of a cnidarian stinging organelle

The stingers of jellyfish, sea anemones and other cnidarians, known as nematocysts, are remarkable cellular weapons used for both predation and defense1. Nematocysts are specialized organelles which consist of a pressurized capsule containing a coiled harpoon-like thread2. These structures are in turn built within specialized cells known as nematocytes3. When triggered4, the capsule explosively discharges, ejecting the coiled thread which punctures the target and rapidly elongates by turning inside out in a process called eversion5,6. Due to the structural complexity of the thread and the extreme speed of discharge, the precise mechanics of nematocyst firing have remained elusive7. Here, using a combination of live and super-resolution imaging, 3D electron microscopy and genetic perturbations, we define the step-by-step sequence of nematocyst operation in the model sea anemone Nematostella vectensis. This analysis reveals the complex biomechanical transformations underpinning the operating mechanism of nematocysts, one of the natures most exquisite biological micro-machines. Further, this study will provide insight into the form and function of related cnidarian organelles and serve as a template for the design of bioinspired microdevices.

cell biology↗

bioRxiv2021

Impact of cilia-related genes on mitochondrial dynamics during Drosophila spermatogenesis

Spermatogenesis is a dynamic process of cellular differentiation that generates the mature spermatozoa required for reproduction. Errors that arise during this process can lead to sterility due to low sperm counts and malformed or immotile sperm. While is estimated that 1 out of 7 couples encounter infertility, the underlying cause of male infertility can only be identified in 50% of cases. Here, we describe and examine the genetic requirements for missing minor mitochondria (mmm), sterile affecting ciliogenesis (sac), and testes of unusual size (tous), three previously uncharacterized genes that are predicted to be components of the flagellar axoneme. Using Drosophila, we demonstrate that these genes are essential for male fertility and that loss of mmm, sac, or tous results in complete immotility of the sperm flagellum. Cytological examination uncovered additional roles for sac and tous during cytokinesis and transmission electron microscopy of developing spermatids in mmm, sac, and tous mutant animals revealed defects associated with mitochondria and the accessory microtubules required for the proper elongation of the mitochondria and flagella during ciliogenesis. This study highlights the complex interactions of cilia-related proteins within the cell body and advances our understanding of male infertility by uncovering novel mitochondrial defects during spermatogenesis.

developmental biology↗

bioRxiv2020

Plasticity in parental effects confers rapid larval thermal tolerance in Nematostella vectensis

Parental effects can prepare offspring for different environments and facilitate survival across generations. We exposed parental populations of the estuarine anemone, Nematostella vectensis, from Massachusetts to elevated temperatures and quantified larval mortality across a temperature gradient. We find that parental exposure to elevated temperatures results in a consistent increase in larval thermal tolerance (mean ΔLT50: 0.3°C), and larvae from subsequent spawns return to baseline thermal thresholds when parents are returned to normal temperatures. Histological analyses of gametogenesis in females suggests these dynamic shifts in larval thermal tolerance may be facilitated by maternal effects in non-overlapping gametic cohorts. We also compared larvae from North Carolina (a genetically distinct population with higher baseline thermal tolerance) and Massachusetts parents, and found larvae from heat-exposed Massachusetts parents have thermal thresholds comparable to larvae from unexposed North Carolina parents. North Carolina parents also increased larval thermal tolerance under the same high-temperature regime, suggesting plasticity in parental effects is an inherent trait for N. vectensis. Overall, we find larval thermal tolerance in N. vectensis shows both a strong genetic basis and phenotypic plasticity. Further understanding the mechanisms behind these shifts can elucidate the fate of thermally sensitive ectotherms in a rapidly changing thermal environment.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗