Biology subjects

Hopkins, C. R.

Publications and source records attributed to Hopkins, C. R..

4 recordsLinked to original sources

bioRxiv2025

Conservation relevant fine scale distribution and habitat associations of threatened elasmobranchs in temperate nearshore waters

Elasmobranchs are globally threatened and experiencing ongoing declines. Understanding threatened elasmobranch distribution is critical for developing effective marine conservation strategies. However, our knowledge of fine scale elasmobranch habitat association and distribution in temperate nearshore systems is limited. Here, we examined the presence, relative abundance and habitat association of sharks, skates and rays using benthic baited remote underwater stereo-video systems (SBRUVs). From 772 deployments (682 total hours, 53 minutes average soak time) across three years (2021-2023) and two Scottish sea lochs and adjacent bays, elasmobranchs were detected on 31.2% of deployments (n = 241). Our surveys detected six species of elasmobranchs, representing 17.6% of the resident elasmobranch diversity reported to date in nearshore waters < 200 m depth in UK waters. The species detected include two species listed as globally Vulnerable on the IUCN Red List, spiny dogfish (Squalus acanthias) and porbeagle (Lamna nasus) and one Critically Endangered species, flapper skate (Dipturus intermedius). Critically Endangered flapper skate were detected in 5.2% deployments (n = 40) and were the only species recorded which did not show a relationship between the probability of presence and substratum type. Our findings provide critical data on the fine scale spatial distribution and habitat use of elasmobranchs, informing evidence-based conservation measures and supporting more consistent and targeted policy action for these species in Scotland.

ecology↗

bioRxiv2025

Just add water: Urban blue spaces increase avian richness and functional diversity

Urban blue spaces are highly valuable for both people and nature, providing key ecosystem services, including flood alleviation, pollution absorption, microclimate regulation, benefits to human health and wellbeing, and habitat provision. Crucially, urban blue spaces support biodiversity, including threatened species, and despite often being small, may have disproportionate effects on their surrounding environment, acting as critical habitats within urban systems. However, research on the role of urban blue spaces within ecological contexts remains limited. Here, we assessed urban bird communities across green and blue spaces to quantify the ecological effects of urban water bodies. We surveyed birds along 22 paired 1 km transects in the city of Kingston Upon Hull, UK, recording species and abundance across both winter and breeding seasons. Our findings indicate that blue spaces significantly increase bird species richness during summer (P = 0.016), though not in winter. However, we found that the taxonomic distinctiveness of bird communities is consistently greater around blue spaces across both seasons (P < 0.05). Similarly, functional diversity based on species-level ecological traits was more varied around water (P = 0.01). In addition, we show that urban blue spaces could be important for avian conservation, supporting more red and amber-listed species than green spaces during the summer (P = < 0.05). Overall, our results show that urban blue spaces play a critical ecological role within cities by enhancing the complexity of avian communities, which in turn could improve human wellbeing and contribute to urban sustainability.

ecology↗

bioRxiv2024

TET2 regulates early and late transitions in exhausted CD8+ T-cell differentiation and limits CAR T-cell function

CD8+ T-cell exhaustion hampers disease control in cancer and chronic infections and limits efficacy of T-cell-based therapies, such as CAR T-cells. Epigenetic reprogramming of CAR T-cells by targeting TET2, a methylcytosine dioxygenase that mediates active DNA demethylation, has shown therapeutic potential; however, the role of TET2 in exhausted T-cell (TEX) development is unclear. In CAR T-cell exhaustion models and chronic LCMV infection, TET2 drove the conversion from stem cell-like, self-renewing TEX progenitors towards terminally differentiated and effector (TEFF)-like TEX. In mouse T-cells, TET2-deficient terminally differentiated TEX retained aspects of TEX progenitor biology, alongside decreased expression of the transcription factor TOX, suggesting that TET2 potentiates terminal exhaustion. TET2 also enforced a TEFF-like terminally differentiated CD8+ T-cell state in the early bifurcation between TEFF and TEX, indicating a broad role for TET2 in mediating the acquisition of an effector biology program that could be exploited therapeutically. Finally, we developed a clinically actionable strategy for TET2- targeted CAR T-cells, using CRISPR/Cas9 editing and site-specific adeno-associated virus transduction to simultaneously knock-in a CAR at the TRAC locus and a functional safety switch within TET2. Disruption of TET2 with this safety switch in CAR T-cells restrained terminal TEX differentiation in vitro and enhanced anti-tumor responses in vivo. Thus, TET2 regulates pivotal fate transitions in TEX differentiation and can be targeted with a safety mechanism in CAR T-cells for improved tumor control and risk mitigation. One Sentence SummaryModulation of exhausted CD8+ T-cell differentiation by targeting TET2 improves therapeutic potential of CAR T-cells in cancer.

immunology↗

bioRxiv2023

Mitigation of chromosome loss in clinical CRISPR-Cas9-engineered T cells

CRISPR-Cas9 genome editing has enabled advanced T cell therapies, but occasional loss of the targeted chromosome remains a safety concern. To investigate whether Cas9-induced chromosome loss is a universal phenomenon and evaluate its clinical significance, we conducted a systematic analysis in primary human T cells. Arrayed and pooled CRISPR screens revealed that chromosome loss was generalizable across the genome and resulted in partial and entire loss of the chromosome, including in pre-clinical chimeric antigen receptor T cells. T cells with chromosome loss persisted for weeks in culture, implying the potential to interfere with clinical use. A modified cell manufacturing process, employed in our first-in-human clinical trial of Cas9-engineered T cells,1 dramatically reduced chromosome loss while largely preserving genome editing efficacy. Expression of p53 correlated with protection from chromosome loss observed in this protocol, suggesting both a mechanism and strategy for T cell engineering that mitigates this genotoxicity in the clinic.

cell biology↗