Biology subjects

Egan, S.

Publications and source records attributed to Egan, S..

9 recordsLinked to original sources

bioRxiv2026

CDKL5 deficiency alters cell subtype-specific molecular programmes and intercellular signalling in the mouse hippocampus

CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental condition characterised by epilepsy, intellectual disability, and motor dysfunction. Loss of CDKL5 leads to altered synapse development, excitatory-inhibitory imbalances and glial changes, but the underlying molecular mechanisms remain incompletely understood, particularly at the level of individual brain cell subtypes. Here, we performed single-nucleus RNA sequencing (snRNA-seq) on the hippocampus of 12 weeks old heterozygous female Cdkl5 exon 6 deletion (Cdkl5tm1.1Joez/J) and wild-type mice to characterise cell-subtype-specific transcriptional alterations associated with CDKL5 deficiency. Analysis of 11,791 high-quality nuclei revealed cell-subtype-specific transcriptional changes across neuronal and non-neuronal populations. Differential expression was most prominent in intratelencephalic and extratelencephalic (IT-ET) glutamatergic neurons, which showed altered expression of genes involved in neuronal signalling and activity-dependent transcription, and in dentate gyrus (DG) neurons, which exhibited coordinated upregulation of multiple ribosomal protein genes. Gene set enrichment analysis revealed broader molecular alterations, with neuronal populations showing recurrent changes in pathways associated with synaptic organisation, neuronal development, axonal and dendritic processes, and neurotransmission. Altered gene expression was also evident among non-neuronal populations, although these displayed fewer changes. CellChat analysis inferred changes in predicted intercellular communication across excitatory and inhibitory neuronal populations, particularly Sema3c signalling, suggesting reorganization of hippocampal neuronal subtypes. These findings provide a single-nucleus transcriptional atlas of the hippocampus in a CDD mouse model. In our dataset, CDKL5 deficiency was associated with cell-subtype-specific alterations in gene expression, including enrichment of gene pathways related to cellular metabolism, neuronal development and synaptic organisation, alongside alteration in predicted intercellular signalling. This dataset provides a resource for investigating the cellular and molecular mechanisms underlying CDD and for prioritising candidate pathways for future therapeutic investigation.

neuroscience↗

bioRxiv2026

The genome of the Delisea pulchra: a resource for the study of chemical host-microbe interactions in red algae

BackgroundRed macroalgae (Rhodophyta) are ecologically and economically important marine primary producers, yet genomic resources for most species remain scarce. Delisea pulchra, a temperate red alga known for its halogenated furanone-based chemical defenses, serves as a model for studying algal-microbe interactions, antifouling mechanisms, and disease dynamics. ResultsHere we present a high-quality genome assembly of this species. The nuclear genome comprises 134 Mbp across 271 contigs with an N50 of 1.47 Mbp and encodes 13,387 predicted protein-coding genes. Comparative genomics with other red algae revealed expansions in gene families involved in DNA methylation, and oxidative stress responses, including glutathione S-transferases and superoxide dismutases. Analysis of glycosyltransferases, sulfatases, and sulfurylases implicated in galactan biosynthesis suggests D. pulchra possesses a complex and potentially novel extracellular matrix. We also identified several vanadium haloperoxidases (vHPOs), heme-dependent haloperoxidases (hHPOs), and two type III polyketide synthase (PKS) genes unique to the D. pulchra, which together represent promising candidate genes for bromofuranone production. ConclusionThe D. pulchra genome provides a foundation for molecular investigations into defense, signaling, and host-microbe interactions. It has been deposited at the European Nucleotide Archive under accession number PRJEB101077. All datasets, annotations, and interactive tools for exploring the genome are also available through the Rhodoexplorer portal at https://rhodoexplorer.sb-roscoff.fr.

genomics↗

bioRxiv2026

VECTR-Clasp: An open machine-learning and vector-based framework for objective quantification of motor dysfunction during hind-limb clasping in Cdkl5-deficient mice

Quantitative assessment of motor behaviour in rodents is central to the study of neurological disease, yet it remains constrained by manual categorical scoring systems that limit sensitivity, reproducibility, and the ability to detect subtle phenotypes. The hind-limb clasping assay, a standard test of motor dysfunction across many mouse models, is typically scored on an observer-defined categorical scale that may overlook meaningful movement features. We developed VECTR-Clasp, an open vector-based geometric framework that transforms standard pose-estimation output into continuous, body-relative kinematic measures. Combining DeepLabCut for markerless pose estimation with SimBA for automated clasping classification, our pipeline first reproduces conventional clasping detection at a level of agreement approaching that between trained human raters, and then extracts continuous geometric descriptors, including head directionality, total distance travelled, and swing count, that are inaccessible to categorical scoring. Applied to a mouse model of CDKL5 deficiency disorder, a rare neurodevelopmental condition in which motor impairment is a core clinical feature, this approach revealed previously uncharacterised motor microphenotypes: affected animals showed more constrained head direction, reduced overall movement, and fewer swings than wildtype controls. Critically, these differences were also present in affected animals that displayed no overt clasping. Together, these findings demonstrate that continuous geometric analysis of pose-estimation data uncovers motor phenotypes beyond the resolution of categorical scales, providing a more sensitive and reproducible framework for quantifying motor dysfunction. As it operates on standard pose-estimation output, the approach extends readily to other behavioural assays, disease models, and the evaluation of therapeutic interventions. Author SummaryMany neurological disorders impair movement, and researchers frequently study these deficits in mouse models. A widely used test lifts a mouse by the tail and records whether it retracts its hind limbs towards its body, a reflex associated with motor dysfunction. Traditionally, an observer watches the animal and assigns a categorical score. This approach depends on human judgement, varies between raters, and can miss subtle movement differences. We developed VECTR-Clasp, an open-source pipeline that validates machine-learning pose tracking to automate traditional clasping assessment and extends current methods using vector-based geometry. This quantifies the direction and extent of head and body movements, providing additional motor readouts. In a mouse model of CDKL5 deficiency disorder, a rare paediatric neurological disorder, VECTR-Clasp matched human scoring while revealing kinematic differences missed by standard assessment, including in animals appearing unaffected. This objective, sensitive framework could detect subtle motor changes and treatment responses across neurological diseases.

neuroscience↗

bioRxiv2026

Dual transcriptomics reveal commensal interactions between microalgae and phycosphere bacteria

The interactions between microalgae and the bacteria living in the phycosphere are pivotal to the role they play in aquatic ecosystems. This study examines how two representatives of common phycosphere bacteria, Yoonia sp. TsM2_T14_4 (Rhodobacteraceae) and Maribacter sp. IgM3_T14_3 (Flavobacteriaceae), interact with three microalgal hosts: Isochrysis galbana, Tetraselmis suecica, and Conticribra weissflogii (formerly Thalassiosira weissflogii) using dual transcriptomic analyses of both bacteria and microalgae. Bacterial transcriptomes differed significantly depending on microalgal host, with notable changes in carbohydrate metabolism among other COG categories. Yoonia sp. expressed genes involved in anoxygenic photosynthesis in co-culture with I. galbana, presumably due to its inability to utilize carbohydrates from this algal host, whereas Maribacter sp. expressed polysaccharide degradation genes in co-culture with C. weissflogii along with T9SS genes, which can be employed to secrete these hydrolytic enzymes. Specifically, a putative glucan endo-1,3-beta-D-glucosidase was highly expressed, an enzyme that can hydrolyze laminarin and curdlan. Maribacter sp. IgM3_T14_3 could utilize laminarin as a sole carbon source in laboratory settings, a polysaccharide commonly found in marine environments and produced by C. weissflogii. Surprisingly, microalgal transcriptomes remained largely unaltered in the presence of either of the bacteria compared to transcriptomes of axenic algal cultures. These findings highlight the adaptability of phycosphere bacteria to different microalgal hosts. Furthermore, it also indicates a commensalism between microalgae, Yoonia sp. and Maribacter sp., in which the bacteria adapt to and benefit from microalgal host exudates, whereas under the conditions employed here the microalgae are unaffected by the presence of these bacterial symbionts. ImportanceMicroalgae are the key players in marine ecosystems, capturing carbon dioxide through photosynthesis and releasing carbohydrates into their immediate environment, the so-called phycosphere. Certain bacterial taxa are consistently found within the phycosphere, where they interact with their microalgal host in a variety of ways. However, the impact of these bacteria on the microalgae is not fully understood despite their ecological relevance. This study uses a dual transcriptomic approach to investigate the impact of such core phycosphere bacteria on microalgal hosts and vice versa to uncover the reason behind their success in the phycosphere and possible roles in marine ecosystems.

microbiology↗

bioRxiv2025

Assigning Targetable Molecular Pathways to Transdiagnostic Subgroups Across Autism and Related Neurodevelopmental Disorders

The heterogeneity of autism and related neurodevelopmental conditions has impeded accurate prognoses and treatment discovery. Using translational neuroimaging across 135 mouse models (3,515 mice) and two human MRI datasets (n = 1,234 and n = 1,015), we derived participant subgroups from shared neuroanatomical features. These subgroups did not distinguish autism, ADHD, or OCD diagnoses and only modestly differentiated cognitive and behavioural phenotypes. Instead, they mapped onto four molecular pathways: (1) synaptic function; (2) MAPK and Wnt signalling; (3) chromatin modification and cellular stress responses; and (4) broader chromatin, immune, and second-messenger signalling pathways. This framework bridges preclinical models and idiopathic human neurodevelopmental conditions, linking patients to biologically relevant molecular mechanisms.

neuroscience↗

bioRxiv2024

Comparative proteomics of biofilm development in Pseudoalteromonas tunicata discovers a distinct family of Ca2+-dependent adhesins

The marine bacterium, Pseudoalteromonas tunicata, is a useful model for studying mechanisms of biofilm development due to its ability to colonize and form biofilms on a variety of marine and eukaryotic host-associated surfaces. However, the pathways responsible for P. tunicata biofilm formation are still incompletely understood, in part due to a lack of functional information for a large proportion of its proteome. Here, we used comparative shotgun proteomics to examine P. tunicata biofilm development throughout the planktonic phase to three stages of biofilm development at 24, 48, and 72 h. Proteomic analysis identified 232 proteins that were up-regulated during different stages of biofilm development, including many hypothetical proteins as well as proteins known to be important for P. tunicata biofilm development such as the autocidal enzyme AlpP, violacein proteins, S-layer protein SLR4, and various pili proteins. We further investigated the top identified biofilm-associated protein (Bap), a previously uncharacterized 1600 amino acid protein (EAR30327), which we designated as "BapP". Based on AlphaFold modeling and genomic context analysis, we predicted BapP as a distinct Ca2+-dependent biofilm adhesin. Consistent with this prediction, a {Delta}bapP knockout mutant was defective in forming both pellicle and surface-associated biofilms, which was rescued by re-insertion of bapP into the genome. Similar to mechanisms of RTX adhesins, BapP-mediated biofilm formation was influenced by Ca2+ levels, and BapP is likely exported by a type 1 secretion system. Ultimately, our work not only provides a useful proteomic dataset for studying biofilm development in an ecologically relevant organism, but it also adds to our knowledge of bacterial adhesin diversity, emphasizing Bap-like proteins as widespread determinants of biofilm formation in bacteria.

microbiology↗

bioRxiv2022

Delimiting the cryptic diversity and host preferences of Sycophila parasitoid wasps associated with oak galls using phylogenomic data

Cryptic species diversity is a major challenge for the species-rich community of parasitoids attacking oak gall wasps due to a high degree of sexual dimorphism, morphological plasticity, small size, and poorly known biology. As such, we know very little about the number of species present, nor the evolutionary forces responsible for generating this diversity. One hypothesis is that trait diversity in the gall wasps, including the morphology of the galls they induce, has evolved in response to selection imposed by the parasitoid community, with reciprocal selection driving diversification of the parasitoids. Using a rare, continental-scale data set of Sycophila parasitoid wasps reared from 44 species of cynipid galls from 18 species of oak across the US, we combined mitochondrial DNA barcodes, Ultraconserved Elements (UCEs), morphological, and natural history data to delimit putative species. Using these results, we generate the first large-scale assessment of ecological specialization and host association in this species-rich group, with implications for evolutionary ecology and biocontrol. We find most Sycophila target specific subsets of available cynipid host galls with similar morphologies, and generally attack larger galls. Our results suggest that parasitoid wasps such as Sycophila have adaptations allowing them to exploit particular host trait combinations, while hosts with contrasting traits are resistant to attack. These findings support the tritrophic niche concept for the structuring of plant-herbivore-parasitoid communities.

evolutionary biology↗

bioRxiv2021

Loss of epigenetic regulation disrupts lineage integrity, reactivatesmultipotency and promotes breast cancer

Systematically investigating the scores of genes mutated in cancer and discerning real drivers from inconsequential bystanders is a prerequisite for Precision Medicine, but remains challenging. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to study 215 recurrent long-tail breast cancer genes, which revealed epigenetic regulation as major tumor suppressive mechanism. We report that core or accessory components of the COMPASS histone methylase complex including KMT2C, KDM6A, BAP1 and ASXL2 ("EpiDrivers") cooperate with PIK3CAH1047R to transform mouse and human breast epithelial cells. Mechanistically, we find that Cre-mediated activation of PIK3CAH1047R elicited an aberrant alveolar lactation program in luminal cells, which was exacerbated upon loss of EpiDrivers. Remarkably, EpiDriver loss in basal cells also triggered an alveolar-like lineage conversion and accelerated formation of luminal-like tumors, suggesting a basal origin for luminal tumors. As EpiDrivers are mutated in 39% of human breast cancers, lineage infidelity and lactation mimicry may significantly contribute to early steps of breast cancer progression. Statement of significanceInfrequently mutated genes comprise most of the mutational burden in breast tumors but are poorly understood. In-vivo CRISPR screening identified functional tumor suppressors that converged on epigenetic regulation. Loss of epigenetic regulators accelerated tumorigenesis and revealed lineage infidelity and aberrant expression of lactation genes as potential early events in tumorigenesis.

cancer biology↗

bioRxiv2019

Revisiting Australian Ectocarpus subulatus (Phaeophyceae) from the Hopkins River: distribution, abiotic environment, and associated microbiota

Ectocarpus is a genus of common marine brown algae. In 1995 a strain of Ectocarpus was isolated from Hopkins River Falls, Victoria, Australia, constituting one of few available freshwater or nearly freshwater brown algae, and the only one belonging to Ectocarpus. It has since been used as a model to study acclimation and adaptation to low salinities and the role of its microbiota in these processes. However, little is known about the distribution of this strain or whether it represents a stable population. Furthermore, its microbiota may have been impacted by the long period of cultivation.\n\nTwenty-two years after the original finding we searched for Ectocarpus in the Hopkins River and surrounding areas. We found individuals with ITS and cox1 sequences identical to the original isolate at three sites upstream of Hopkins River Falls, but none at the original isolation site. The osmolarity of the water at these sites ranged from 74-170 mOsmol, and it was rich in sulfate. The diversity of bacteria associated with the algae in situ was approximately one order of magnitude higher than in previous studies of the original laboratory culture, and 95 alga-associated bacterial strains were isolated from E. subulatus filaments on site. In particular, Planctomycetes were abundant in situ but rare in the laboratory-cultured strain.\n\nOur results confirm that E. subulatus has stably colonized the Hopkins River, and the newly isolated algal and bacterial strains offer new possibilities to study the adaptation of Ectocarpus to low salinity and its interactions with its microbiome.

plant biology↗