Biology subjects

Campbell, L.

Publications and source records attributed to Campbell, L..

17 recordsLinked to original sources

bioRxiv2026

A novel lineage of Chilomastix mesnili in wild Moroccan Barbary macaques (Macaca sylvanus)

Chilomastix spp. are flagellated protists found in the intestines of a broad range of hosts. They are generally non-pathogenic and have been little studied, especially using molecular techniques, and significant taxonomic uncertainty regarding the host specificity of lineages remains. As part of a study of intestinal microbial communities of wild Barbary macaques (Macaca sylvanus) from Morocco, we mined 50 faecal metagenomic sequence libraries and found 11 rRNA sequences matching Chilomastix. Compared to published 18S rRNA sequences, the Barbary macaque Chilomastix sequences formed a well-supported clade distinct from human-derived C. mesnili ST1 from Indonesia. The macaque Chilomastix sequences cluster with a single pig-derived isolate and two sequences from Japanese macaques (Macaca fuscata). This indicates that M. sylvanus harbours a lineage of Chilomastix distinct from the common human strain of C. mesnili and geographically widespread. We were also able to reconstruct the complete rDNA operon from this lineage.

evolutionary biology↗

bioRxiv2026

ProteomeScout v4: An open-source, harmonized, ecosystem for post-translational modifications

There are many databases of post-translational modifications, but each has different protein and PTM coverage, making the current state of post-translational modifications difficult to obtain, assess, or harmonize. ProteomeScout has been a relational database that harmonized a myriad of resources to address this challenge. In this update, we wished to create a lightweight, sustainable open source resource for the community that retained the power of harmonization, protein visualization, and Python tools for interacting with the database. ProteomeScout-v4 presents an ecosystem of open-source tools for aggregating and updating proteins and post-translational modifications and presenting the web-based and code-based access tools for interacting with the data. ProteomeScout has moved from using a complex relational database to a flat-text file format. The database file update is version controlled on FigShare and all features have processes for continuous updating, including migrating PTMs to updated protein records, when external databases are updated. The open-source nature and flexibility allow for user-based control and community-based feature integration. Fast and easy analysis is possible with the API, with example analyses provided here.

systems biology↗

bioRxiv2026

Chytridiomycosis infection and heat compromises sperm quality in a threatened frog

Environmental change is reshaping wildlife reproduction through increasing temperatures and the spread of emerging infectious diseases, yet the physiological consequences of managing these stressors remain poorly understood. Amphibians are particularly vulnerable due to their ectothermy and high susceptibility to chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd). Here, we examine how Bd infection and thermal treatment interact to influence sperm quality and reproductive investment in male green and golden bell frogs (Ranoidea aurea), a species that has suffered severe population declines. Moderate Bd infection was associated with elevated sperm concentration relative to uninfected and heavily infected males, consistent with increased short-term reproductive investment under elevated mortality risk. However, severe infection led to pronounced reductions in sperm concentration and motility. Thermal treatment successfully eliminated Bd infection but imposed substantial reproductive costs: sperm concentration declined following treatment and remained significantly reduced six months later, despite partial recovery of sperm motility and membrane integrity. These results indicate persistent impairment of spermatogenic capacity rather than transient suppression. Our findings reveal that disease and thermal stress jointly shape amphibian reproductive outcomes through context-dependent trade-offs between immune defence and gamete production. While mild infection may trigger short-lived increases in reproductive output, both severe infection and pathogen clearance via thermal exposure impose lasting constraints on fertility. These results highlight an underappreciated cost of disease mitigation and suggest that increasing thermal extremes associated with climate change may further limit amphibian reproductive resilience, with important implications for conservation management and population persistence.

physiology↗

bioRxiv2025

Caecal epithelium-derived thymic stromal lymphopoietin is not required for protective immunity against whipworm

Recent research examining classical type two alarmin TSLP has uncovered non-epithelial cellular sources of the cytokine during various murine challenges. Trichuris muris is a key model of type two immunity in the intestine with expulsion being TSLP-dependent. Previous research was suggestive of epithelial production of TSLP in the caecum, but its production during infection has not been characterised in detail. Here, using qPCR, transcript-based imaging, and conditional knockout, we demonstrate caecal epithelium to be a poor source of Tslp, and that non-epithelial upregulation occurs during Trichuris infection, peaking around day 14 post-infection. Conditional knockout of TSLP expression in caecal epithelial cells did not here impact parasite expulsion, but, surprisingly, neutralisation of TSLP from days 15 to 25 produced full susceptibility. These data build on previous work to raise important questions regarding the interaction of TSLP with immunity broadly, as well as the conditions for production of immunity to intestinal helminths.

immunology↗

bioRxiv2025

A high-quality reference genome and tissue expression atlas for the European lobster (Homarus gammarus)

The European lobster (Homarus gammarus) and its sister species, the American lobster (Homarus americanus), are notable for their remarkable immunity and longevity, with lifespans reaching up to 80 years in the wild. A reference genome is available for the American lobster, but not yet for the European lobster, despite its ecological significance, and importance to fisheries and aquaculture. Here, we present a high-quality genome assembly and annotation for the European lobster. The assembly spans 1.76 Gb, with a scaffold N50 of 1.82 Mb and a BUSCO completeness of 97.6%. As observed in the American lobster, the total assembly span is substantially smaller than genome size estimates derived from flow cytometry, performed using independently sampled European lobsters (3.18 - 3.42 Gb). This discrepancy may reflect the highly repetitive nature of decapod genomes, with 51.8% of the H. gammarus assembly consisting of repetitive elements. Leveraging a comprehensive multi-tissue RNA-seq dataset, we annotated 23,223 protein-coding genes and characterised gene expression across ten tissues to generate a tissue-level gene expression atlas, available at www.LobsterGeneX.com. Using single-copy orthologs, we estimated a divergence time of 26 Mya (95% HPD 22 - 30 Mya) between H. gammarus and H. americanus, corresponding to the Oligocene-Miocene boundary. We also identified Homarus-specific gene duplications with roles in immunity and longevity, including telomere maintenance. The reported genomic resources can facilitate future research into lobster biology, support sustainable fisheries and aquaculture management practices, and enable investigations of the evolutionary mechanisms underlying basic biological processes, notably immunity and longevity in Homarid lobsters. Significance StatementThe European lobster (Homarus gammarus) and the American lobster (Homarus americanus) are large benthic decapod crustaceans with significant seafood value, known for their remarkable longevity, with typical lifespans of 30-55 years in the wild and maximum lifespans of up to 80 years. Lobsters grow, reproduce and regenerate limbs throughout their life, and there are very few reports of tumours or age-related diseases. We generated and herein share a high-quality genome assembly and annotation for the European lobster alongside a tissue expression atlas, LobsterGeneX, which enables the visualisation of gene expression profiles across ten tissue types. Based on the genetic information generated, we also provide an estimated time for the divergence between H. gammarus and H. americanus (26 Mya) and identify duplication events for genes related to immunity and longevity. The European lobster reference genome will facilitate further research for investigations into local adaptation in lobster populations, genomic mixing in Homarid hybrids, and identification of genes of interest in aquaculture, ageing, regeneration, disease and cancer resistance.

genomics↗

bioRxiv2025

Comparative single-cell multiomic analysis reveals evolutionarily conserved and species-specific cellular mechanisms mediating natural retinal aging.

Biological age is a major risk factor in the development of common degenerative retinal diseases such as age-related macular degeneration and glaucoma. To systematically characterize molecular mechanisms underlying retinal aging, we performed integrated single- cell RNA- and ATAC-Seq analyses of the retina and retinal pigment epithelium (RPE) across the natural lifespan in zebrafish, mice, and humans. By profiling gene expression and chromatin accessibility, we identified extensive cell type- and species-specific aging-dependent changes, with a much smaller number of broadly expressed and conserved genes that include regulators of inflammation and autophagy. We constructed predictive aging clocks for retinal cell types and observed dynamic, reversible shifts in cellular age following acute injury. Spatial transcriptomic analysis revealed region-specific aging signatures and proximity effects, with Muller glia exhibiting pro-rejuvenating influences on neighboring neurons. Targeted Muller glia-specific induction of Yamanaka factors reduced molecular age in rod photoreceptors and bipolar cells without altering glial age. Our findings define conserved and divergent regulatory and signaling pathways mediating retinal aging, highlighting Muller glia as potential therapeutic targets for combating age-associated retinal dystrophies.

neuroscience↗

bioRxiv2024

A continuation of the assembly of a G-quadruplex repair complex by the FANCJ DNA helicase

Guanine-rich nucleic acid sequences can adopt G-quadruplex (G4) structures, which pose barriers to DNA replication and repair. The FANCJ helicase contributes to genome stability by resolving these structures, a function linked to its G4-binding site that features an AKKQ amino acid motif. This site is thought to recognize oxidatively damaged G4, specifically those containing 8-oxoguanine (8oxoG) modifications. We hypothesize that FANCJ AKKQ recognition of 8oxoG-modified G4s (8oxoG4s) depends on the sequence context, the position of the lesion within the G4, and overall structural stability. Using fluorescence spectroscopy, we measured the binding affinities of a FANCJ AKKQ peptide for G4s formed by (GGGT)4, (GGGTT)4, and (TTAGGG)4 sequences. G4 conformation and thermal stability were assessed by circular dichroism spectroscopy. Each sequence was modified to include a single 8oxoG at the first (8oxo1), third (8oxo3), or fifth (8oxo5) guanine position. In potassium chloride (KCl), the most destabilized structures were (GGGT)4 8oxo1, (GGGTT)4 8oxo1, and (TTAGGG)4 8oxo5. In sodium chloride (NaCl), the most destabilized were (GGGT)4 8oxo1, (GGGTT)4 8oxo5, and (TTAGGG)4 8oxo5. FANCJ AKKQ binding affinities varied according to damage position and sequence context, with notable differences for (GGGT)4 in KCl and (TTAGGG)4 in NaCl. These findings support a model in which FANCJ binding to G4 and 8oxoG4 structures is modulated by both the oxidative damage position and the G4 local sequence environment.

biochemistry↗

bioRxiv2024

CoDIAC: A comprehensive approach for interaction analysis reveals novel insights into SH2 domain function and regulation

Protein domains are conserved structural and functional units that serve as building blocks of proteins. Through evolutionary expansion, domain families are represented by multiple members in diverse configurations with other domains, evolving new specificities for their interacting partners. Here, we develop a structure-based interface analysis to comprehensively map domain interfaces from experimental and predicted structures, including interfaces with macromolecules and intraprotein interfaces. We hypothesized that comprehensive contact mapping of domains could yield new insights into domain selectivity, conservation of domain-domain interfaces across proteins, and identify conserved post-translational modifications (PTMs), relative to interaction interfaces, allowing for the inference of specific effects due to PTMs or mutations. We applied this approach to the human SH2 domain family, a modular unit central to phosphotyrosine-mediated signaling, identifying a novel approach to understanding binding selectivity and evidence of coordinated regulation of SH2 domain binding interfaces by tyrosine and serine/threonine phosphorylation and acetylation. These findings suggest multiple signaling systems can regulate protein activity and SH2 domain interactions in a coordinated manner. We provide the extensive features of the human SH2 domain family and this modular approach as an open source Python package for COmprehensive Domain Interface Analysis of Contacts (CoDIAC).

systems biology↗

bioRxiv2024

BRCA1 interaction with Non-Canonical DNA Structures: Insights into Genome Maintenance and Disease Mechanisms

BRCA1 is a crucial mediator of homologous recombination (HR), a high-fidelity pathway for repairing double-stranded DNA breaks (DSBs) in human cells. The central region of BRCA1 protein contains two putative DNA binding domains (DBDs), yet their relative substrate specificities and functional contributions to HR remain unclear. Here, we characterized the DNA binding properties of DBD1 (amino acids 330-554), DBD2 (amino acids 894-1057), and the BRCA1 C-terminal (BRCT) repeats using biolayer interferometry. We assessed their affinities for single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), and G-quadruplex (G4) structures. DBD1 exhibited the highest affinity for dsDNA, while DBD2 and BRCT bound preferentially to ssDNA and G4. These findings support a model in which DBD1 directs BRCA1 to DSB sites to facilitate DNA end resection during HR, whereas DBD2 and BRCT contribute to the role of BRCA1 in telomere maintenance and chromatin remodeling through the recognition of non-canonical DNA structures.

biochemistry↗

bioRxiv2023

Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer

The current study in prostate cancer (PCa) focused on the genomic mechanisms at the cross-roads of pro-differentiation signals and the emergence of lineage plasticity. We explored an understudied cistromic mechanism involving RAR{gamma}s ability to govern AR cistrome-transcriptome relationships, including those associated with more aggressive PCa features. The RAR{gamma} complex in PCa cell models was enriched for canonical cofactors, as well as proteins involved in RNA processing and bookmarking. Identifying the repertoire of miR-96 bound and regulated gene targets, including those recognition elements marked by m6A, revealed their significant enrichment in the RAR{gamma} complex. RAR{gamma} significantly enhanced the AR cistrome, particularly in active enhancers and super-enhancers, and overlapped with the binding of bookmarking factors. Furthermore, RAR{gamma} expression led to nucleosome-free chromatin enriched with H3K27ac, and significantly enhanced the AR cistrome in G2/M cells. RAR{gamma} functions also antagonized the transcriptional actions of the lineage master regulator ONECUT2. Similarly, gene programs regulated by either miR-96 or antagonized by RAR{gamma} were enriched in alternative lineages and more aggressive PCa phenotypes. Together these findings reveal an under-investigated role for RAR{gamma}, modulated by miR-96, to bookmark enhancer sites during mitosis. These sites are required by the AR to promote transcriptional competence, and emphasize luminal differentiation, while antagonizing ONECUT2.

cancer biology↗

bioRxiv2023

Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina.

Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes. This regeneration requires Muller glia (MG) to reprogram and divide asymmetrically to produce a multipotent Muller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, does loss of different retinal cell subtypes induce unique MG regeneration responses? Second, do MG reprogram to a developmental retinal progenitor cell state? And finally, to what extent does regeneration recapitulate retinal development? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. While MG reprogram to a state similar to late-stage retinal progenitors in developing retinas, there are transcriptional differences between reprogrammed MG/MGPCs and late progenitors, as well as reprogrammed MG in outer and inner retinal damage models. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes. This work identifies major differences between gene regulatory networks activated following the selective loss of different subtypes of retina neurons, as well as between retinal regeneration and development.

neuroscience↗

bioRxiv2022

Preparing future STEM faculty nationwide through flexible teaching professional development

We report on a five-year initiative that has prepared thousands of future STEM faculty around the world to adopt evidence-based instructional practices by participating in two massive open online courses (MOOCs) and facilitated in-person learning communities. This novel combination of asynchronous online and coordinated, structured face-to-face learning community experiences provides flexible options for STEM graduate students and postdoctoral fellows to pursue teaching professional development, while leveraging the affordances of educational technologies and the geographically clustered nature of this target learner demographic. A total of 14,977 participants enrolled in seven offerings of the introductory course held 2014-2018, with 1,725 participants from approximately 60 countries completing at an average course completion rate of 13%. The preparation of future STEM faculty makes an important difference in establishing high-quality instruction that meets the diverse needs of all undergraduate students, and the initiative described here can serve as a model for increasing access to such preparation.

scientific communication and education↗

bioRxiv2022

Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS and sporadic congenital heart disease

BackgroundCongenital heart disease (CHD) affecting the conotruncal region of the heart, occur in half of patients with 22q11.2 deletion syndrome. This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, mapped to the 22q11.2 region, encoding a T-box transcription factor, is one of the main genes for the etiology of the syndrome. We suggest that genetic modifiers of CHD in patients with 22q11.2 deletion syndrome may be in the TBX1 gene network. MethodsTo identify genetic modifiers of 22q11.2 deletion syndrome, we analyzed whole genome sequence of subjects with 22q11.2DS, of which 456 were cases with conotruncal heart defects and 537 were controls with normal cardiac structures. We retained the most damaging rare coding variants and examined 19 functional gene sets for association that were weighted upon expression of genes in cardiac progenitor cells in mouse embryos identified by RNA-sequencing. ResultsWe identified rare damaging coding variants in chromatin regulatory genes as modifiers of conotruncal heart defects in 22q11.2DS. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2 deletion syndrome cases. Many of these genes were identified as risk factors for sporadic CHD in the general population increasing the likelihood that these genes are medically important contributors for CHD. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. Some of the genes identified, such as KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models, providing mechanistic validation of these genes found. ConclusionsOur findings indicate that disturbance of chromatin regulatory genes impact a TBX1 gene network serving as genetic modifiers of 22q11.2 deletion syndrome. Since some of these chromatin regulatory genes were found in individuals with sporadic CHD, we suggest that there are shared mechanisms involving the TBX1 gene network in the etiology of CHD.

genetics↗

bioRxiv2021

The mitochondrial calcium uniporter regulates mitochondrial mass and dendritic localization in distinct hippocampal circuits

CA2 is an understudied subregion of the hippocampus that is critical for social memory. Previous studies identified multiple components of the mitochondrial calcium uniporter (MCU) complex as selectively enriched in CA2, however the functional significance of this enrichment remains unclear. The MCU complex regulates calcium entry into mitochondria, which in turn regulates mitochondrial transport and localization to active synapses. We found that MCU is strikingly enriched in CA2 distal apical dendrites, precisely where CA2 neurons receive entorhinal cortical input carrying social information. Further, MCU-enriched mitochondria in CA2 distal dendrites are larger compared to mitochondria in CA2 proximal apical dendrites and neighboring CA1 apical dendrites, an effect also seen with genetically labeled mitochondria and electron microscopy. MCU overexpression in neighboring CA1 led to larger mitochondria preferentially in proximal dendrites compared to distal dendrites and controls, suggesting that MCU may act as a coincidence detector linking synaptic activity to mitochondrial morphology and function. Our findings demonstrate that mitochondria are molecularly and structurally diverse across hippocampal cell types and circuits, and implicate MCU expression in regulating mitochondrial mass and layer-specific dendritic localization. Functionally distinct mitochondria in CA2 distal dendrites may confer unique synaptic and circuit properties underlying CA2 function in social memory.

neuroscience↗

bioRxiv2020

T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo

Innate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are "fate-mapped" for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces. SUMMARYInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Three distinct ILC groups have been described according to expression of subset defining transcription factors and other markers. In this study we characterize a novel ILC subset with characteristics of group 1 and group 2 ILC in vivo.

immunology↗

bioRxiv2019

Survey of intertidal ecosystem reveals a legacy of potentially toxic elements from industrial activity in the Skeena Estuary, British Columbia, Canada

Relationships between concentrations of Potentially Toxic Elements (PTEs) in estuarine sediments and their impact benthic invertebrate communities are poorly understood. We sampled and analysed PTEs in sediments and benthic invertebrates from five sites surrounding the Skeena Estuary, including sites adjacent to an abandoned cannery and a decommissioned papermill. There was no indication that sediments of the salmon cannery are polluted, but acidic sediments adjacent to the papermill contained elevated concentrations of Cd, Cr, Hg and Pb. Benthic invertebrate community assemblages confirm that sediments have recovered from prior disturbances associated with discharge of papermill sludge. Oregon pill bugs (Gnorimosphaeroma oregonensis), observed at all five sites, feed on the fibers associated with the papermill discharge. Thus, G. oregonensis are useful biomonitors for quantifying the impact of the decommissioned papermill, and similar industrial development projects, on intertidal ecosystems along the north coast of British Columbia, Canada.

ecology↗

bioRxiv2018

The genome of the biting midge Culicoides sonorensis and gene expression analyses of vector competence for Bluetongue virus

BackgroundThe use of the new genomic technologies has led to major advances in control of several arboviruses of medical importance such as Dengue. However, the development of tools and resources available for vectors of non-zoonotic arboviruses remains neglected. Biting midges of the genus Culicoides transmit some of the most important arboviruses of wildlife and livestock worldwide, with a global impact on economic productivity, health and welfare. The absence of a suitable reference genome has hindered genomic analyses to date in this important genus of vectors. In the present study, the genome of Culicoides sonorensis, a vector of bluetongue virus (BTV) in the USA, has been sequenced to provide the first reference genome for these vectors. In this study, we also report the use of the reference genome to perform initial transcriptomic analyses of vector competence for BTV.\n\nResultsOur analyses reveal that the genome is 197.4 Mb, assembled in 7,974 scaffolds. Its annotation using the transcriptomic data generated in this study and in a previous study has identified 15,629 genes. Gene expression analyses of C. sonorensis females infected with BTV performed in this study revealed 165 genes that were differentially expressed between vector competent and refractory females. Two candidate genes, glutathione S-transferase (gst) and the antiviral helicase ski2, previously recognized as involved in vector competence for BTV in C. sonorensis (gst) and repressing dsRNA virus propagation (ski2), were confirmed in this study.\n\nConclusionsThe reference genome of C. sonorensis has enabled preliminary analyses of the gene expression profiles of vector competent and refractory individuals. The genome and transcriptomes generated in this study provide suitable tools for future research on arbovirus transmission. These provide a significant resource for these vector lineage, which diverged from other major Dipteran vector families over 200 million years ago. The genome will be a valuable source of comparative data for other important Dipteran vector families including mosquitoes (Culicidae) and sandflies (Psychodidae), and yield potential targets for transgenic modification in vector control and functional studies.

genomics↗