Biology subjects

Bell, C. A.

Publications and source records attributed to Bell, C. A..

4 recordsLinked to original sources

bioRxiv2025

Exosome-mediated delivery of microRNAs by root-knot nematodes

Plant-parasitic nematodes secrete molecules to manipulate their hosts, but little is known about their mode of delivery and packaging. Here, we describe microRNA-containing exosomes that are secreted by root-knot nematodes and systemically increase host susceptibility. By revealing a novel mode of nematode-plant communication, our findings outline a mechanism for the delivery of nematode patho-molecules, offering a new target for disrupting parasitism at the level of vesicle-mediated delivery.

pathology↗

bioRxiv2025

A Standardized Protocol to Investigate Trans-Endothelial Trafficking in Zebrafish: Nano-bio Interactions of PEG-based Nanoparticles in Live Vasculature

Trans-endothelial transport of nanoparticles remains poorly characterized in live organisms. The zebrafish is a well-established model for direct in vivo imaging; however, standardized controls are not consistently applied across studies. Here, we developed a standardized protocol to assess nanoparticle trans-endothelial trafficking in live zebrafish. We tested a range of tracers and identified 2000 kDa dextran as an optimal control for standardizing microinjections and quantifying nanoparticle transport in a systematic unbiased manner. As validation, we identified the early physiological trans-endothelial transport pathways in zebrafish embryos using 40 kDa dextran as a nanoparticle surrogate. Using our workflow, we assessed the extravasation of 3, 7, 32 and 47 nm polyethylene glycol (PEG)-based nanoparticles. Using cAMP stimulation to restrict paracellular routes, and inhibitors to impede dynamin-dependent endocytosis, we demonstrated that PEG-based hyperbranched polymer (HBP) nanoparticles of 3 to 7 nm traverse the endothelial barrier via paracellular routes and 32 and 47 nm PEG micelles adopt dynamin- dependent endocytic trafficking over paracellular transport. We characterized the emergence of caveolae in the vasculature up to 17 days post-fertilization (dpf) using a cavin1b knock-in zebrafish line. Using cavin1a/cavin1b double knockout (DKO) zebrafish, and tumor-bearing Cavin-1 null mice, we showed that caveolae do not contribute to the transvascular transport of these PEG-based nanoparticles. This work highlights the rigour of the standardized protocol for assessing nanoparticle trans-endothelial transport in the live zebrafish, providing a systematic approach for quantification using a standardized control.

cell biology↗

bioRxiv2024

The use of X-ray Computed Tomography revolutionises soil pathogen detection

Potato cyst nematodes (PCN), namely Globodera pallida, pose a significant threat to potato production worldwide. Accurately quantifying nematode population densities is crucial for effective management strategies. However, traditional detection methods are time-consuming and often imprecise. X-ray computed tomography (CT) offers high-resolution, non-destructive and three-dimensional (3D) imaging frequently used to visualise internal structures of objects, materials or biological tissues, allowing for detailed analysis of their composition, defects, and morphology. Here, we demonstrate the effectiveness of X-ray CT in detecting and quantifying PCN cysts in different soil types. The ability to achieve 3D imaging and volume quantification of PCN cysts from soils allows accurate enumeration of their egg content. To explore future potential, we propose that when integrated with AI-led quantification of X-ray CT-generated cyst counts, this method could evolve into a next-generation technology to accurately and rapidly quantify these damaging pests in agricultural soils. Combined with the potential to co-analyse other organisms within the same sample, we propose X-ray CT as a fundamental tool for comprehensive soil health assessments and sustainable pest management in agriculture. Author SummaryPotato cyst nematodes are a major threat causing significant crop losses worldwide. Traditionally, detecting this pathogen in soil is challenging, often requiring time-consuming and imprecise. Our study explores a new approach using X-ray computed tomography (CT), a powerful imaging tool that creates detailed 3D images in situ. We observed that X-ray CT can effectively detect and measure the cysts nematodes, even within different soil types. This detailed analysis allows us to determine the cyst structures and estimate the eggs contained. In the future, combining X-ray CT with artificial intelligence could make detecting and quantifying these nematodes even faster and more accurate. This method could also be expanded to study other soil organisms, making it a valuable tool for monitoring soil health and improving agricultural pest management.

plant biology↗

bioRxiv2021

Allele-specific epigenetic activity in prostate cancer and normal prostate tissue implicates prostate cancer risk mechanisms

BackgroundGenome-wide association studies of prostate cancer have identified >250 significant risk loci, but the causal variants and mechanisms for these loci remain largely unknown. Here, we sought to identify and characterize risk harboring regulatory elements by integrating epigenomes from primary prostate tumor and normal tissues of 27 patients across the H3K27ac, H3K4me3, and H3K4me2 histone marks and FOXA1 and HOXB13 transcription factors. ResultsWe identified 7,371 peaks with significant allele-specificity (asQTL peaks). Showcasing their relevance to prostate cancer risk, H3K27ac T-asQTL peaks were the single annotation most enriched for prostate cancer GWAS heritability (40x), significantly higher than corresponding non-asQTL H3K27ac peaks (14x) or coding regions (14x). Surprisingly, fine-mapped GWAS risk variants were most significantly enriched for asQTL peaks observed in tumors, including asQTL peaks that were differentially imbalanced with respect to tumor-normal states. These data pinpointed putative causal regulatory elements at 20 GWAS loci, of which 11 were detected only in the tumor samples. More broadly, tumor-specific asQTLs were enriched for expression QTLs in benign tissues as well as accessible regions found in stem cells, supporting a hypothesis where some germline variants become reactivated during/after transformation and can be captured by epigenomic profiling of the tumor. ConclusionOur study demonstrates the power of allele-specificity in chromatin signals to uncover GWAS mechanisms, highlights the relevance of tumor-specific regulation in the context of cancer risk, and prioritizes multiple loci for experimental follow-up.

cancer biology↗