Biology subjects

Dell, A.

Publications and source records attributed to Dell, A..

14 recordsLinked to original sources

bioRxiv2026

Ecological and evolutionary drivers of thermal performance curves across the tree of life

Biological rates typically follow a unimodal thermal performance curve (TPC), yet the ecological and evolutionary drivers shaping TPC variation remain poorly understood. We compiled an extensive thermal response database covering 896 TPCs for 416 species and 60 traits, spanning microbes to multicellular organisms. Our analyses reveal three key insights. First, environmental seasonality strongly structures TPCs: species in stable environments exhibit narrower thermal ranges and greater asymmetry, with environmental temperature outperforming latitude as a predictor. Second, trait type and organismal complexity modulate thermal sensitivity: emergent traits have narrower ranges than physiological traits, and complex organisms display reduced heat tolerance. Third, prokaryotes and eukaryotes differ fundamentally: while prokaryotes shift thermal limits symmetrically, eukaryotes show constrained upper limits relative to cold tolerance. These findings highlight how environmental stability, trait organization, and evolutionary history shape species thermal niches, providing crucial insights into vulnerability and adaptation under climate change.

ecology↗

bioRxiv2026

Arthritis-Associated Inflammation Remodels Colonic O-Glycosylation

The gut-joint axis describes how impaired intestinal epithelial function and increased gut permeability allow luminal factors to enter circulation. This can drive inflammation in Rheumatoid Arthritis, a chronic condition affecting the joint with systemic features. What mechanisms contribute to disease persistence are, as yet, incompletely understood. In health, extensively Oglycosylated intestinal mucins are central to epithelial protection and immune homeostasis; however, whether mucin glycosylation is altered during arthritis has not been addressed. Here, we investigated whether arthritisassociated inflammation alters mucin Oglycosylation, potentially compromising intestinal barrier function. Using a collageninduced arthritis mouse model, we combined epithelial transcriptomics, mass spectrometry-based glycomics, and imaging approaches to profile intestinal glycosylation. We identified distinct glycan remodeling in the colon, characterized by reduced fucosylation, while the ileum remained largely unaffected. In vitro studies using 3D human epithelial cultures further demonstrated that inflammatory cues, particularly from TNFactivated stromal cells, are sufficient to reduce epithelial fucosylation. Together, these findings identify a stromal-inflammatory mechanism that disrupts mucin glycosylation during arthritis. Loss of colonic fucosylation emerges as a novel element of inflammatory arthritis, providing an additional mechanistic link between intestinal inflammation and fibroblast-dependent modulation of the tissue microenvironment.

immunology↗

bioRxiv2025

H3N2 influenza virus tropism shifts to glycan receptors on tracheal ciliated cells

Human H3N2 influenza viruses, introduced during the 1968 pandemic, have evolved to recognize human-type sialic acid-containing receptors (Neu5Ac2-6Gal) extended with at least three LacNAc (Gal{beta}1-4GlcNAc) repeats. To investigate this restriction in the context of virus attachment to the airway epithelium, we comprehensively analyzed the glycome of human nasal and tracheal epithelial cells. Using a synthetic N-glycan library that reflects the structural diversity of the human airway glycome, we found that only bi-antennary N-glycans with extended human-type receptors on at least one branch serve as receptors for the recent H3 hemagglutinins (HAs). Such receptors are found on tracheal epithelium but are deficient in nasal epithelium. Immunofluorescence analysis on human trachea reveals that recent H3 HAs preferentially attach to ciliated cells, consistent with single-cell RNA sequencing analysis indicating that these cells express glycosyltransferases that produce extended glycan chains. These findings suggest that H3N2 viruses have developed a tropism for tracheal ciliated cells. (146 words)

microbiology↗

bioRxiv2023

Decreased fucosylation impacts epithelial integrity and increases risk for COPD.

COPD causes significant morbidity and mortality worldwide. Epithelial damage is fundamental to disease pathogenesis, although the mechanisms driving disease remain undefined. Published evidence from a COPD cohort (SPIROMICS) and confirmed in a second cohort (COPDgene) demonstrate a polymorphism in Fucosyltransferese-2 (FUT2) is a trans-pQTL for E-cadherin, which is critical in COPD pathogenesis. We found by MALDI-TOF analysis that FUT2 increased terminal fucosylation of E-cadherin. Using atomic force microscopy, we found that FUT2-dependent fucosylation enhanced E-cadherin-E-cadherin bond strength, mediating the improvement in monolayer integrity. Tracheal epithelial cells from Fut2-/- mice have reduced epithelial integrity, which is recovered with reconstitution of Fut2. Overexpression of FUT2 in COPD derived epithelia rescues barrier function. Fut2-/- mice show increased susceptibility in an elastase model of disease developing both emphysema and fibrosis. We propose this is due to the role of FUT2 in proliferation and cell differentiation. Overexpression of FUT2 significantly increased proliferation. Loss of Fut2 results in accumulation of Spc+ cells suggesting a failure of alveolar type 2 cells to undergo transdifferentiation to alveolar type 1. Using a combination of population data, genetically manipulated mouse models, and patient-derived cells, we present a novel mechanism by which post-translational modifications modulate tissue pathology and serve as a proof of concept for the development of a disease-modifying target in COPD.

cell biology↗

bioRxiv2021

Development of a novel glycoengineering platform for the rapid production of conjugate vaccines.

Antimicrobial resistance (AMR) is threatening the lives of millions worldwide. Antibiotics which once saved countless lives, are now failing, ushering in vaccines development as a current global imperative. Conjugate vaccines produced either by chemical synthesis or biologically in Escherichia coli cells, have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccines assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel method that overcomes the limitations of the current conjugate vaccine design method(s). We demonstrate at least 2-fold increase in glycoconjugate yield via MAGIC when compared to conventional bioconjugate method(s). Furthermore, the modularity of the MAGIC platform also allowed us to perform glycoengineering in genetically intractable bacterial species other than E. coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against bacteria, especially AMR pathogens, and could be applied for biopreparedness.

microbiology↗

bioRxiv2020

Efficient Inhibition of O-glycan biosynthesis using the hexosamine analog Ac5GalNTGc

There is a critical need to develop small molecule inhibitors of mucin-type O-linked glycosylation. The best known reagent currently is peracetylated benzyl-GalNAc, but it is only effective at millimolar concentrations. This manuscript demonstrates that Ac5GalNTGc, a peracetylated C-2 sulfhydryl substituted GalNAc, fulfills this unmet need. When added to cultured leukocytes, breast and prostate cells, Ac5GalNTGc increased cell surface VVA-binding by ~10-fold, indicating truncation of O-glycan biosynthesis. Cytometry, mass spectrometry and Western blot analysis of HL-60 promyelocytes demonstrate that 50-80M Ac5GalNTGc prevented elaboration of 30-60% of the O-glycans beyond the Tn-antigen (GalNAc1-Ser/Thr) stage. The effect of the compound on N-glycans and glycosphingolipids was small. Glycan inhibition induced by Ac5GalNTGc resulted in 50-80% reduction in leukocyte sialyl-Lewis-X expression, and L-/P-selectin mediated rolling under flow. Ac5GalNTGc was pharmacologically active in mouse. It reduced neutrophil infiltration to sites of inflammation by ~60%. Overall, Ac5GalNTGc may find diverse applications as a potent inhibitor of O-glycosylation.

biochemistry↗

bioRxiv2020

High mannose N-glycans on red blood cells as phagocytic ligands, mediating both sickle cell anaemia and resistance to malaria

In both sickle cell disease (SCD) and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. Extravascular haemolysis in SCD correlates with high mannose glycan levels on RBCs. Infection of RBCs with Plasmodium falciparum expose surface mannose N-glycans on healthy RBCs, which occurred at significantly higher levels on RBCs from subjects with sickle cell trait compared to those lacking haemoglobin S. The glycans were associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans, a novel response to cellular stress, is the first molecular mechanism common to both the pathogenesis of SCD and resistance to severe malaria in sickle cell trait.

immunology↗

bioRxiv2020

Proteome-wide prediction of bacterial carbohydrate-binding proteins as a tool for understanding commensal and pathogen colonisation of the vaginal microbiome

Bacteria use protein receptors called lectins to anchor to specific host surface sugars. The role of lectins in the vaginal microbiome, and their involvement in reproductive tract pathophysiology is poorly defined. Here we establish a classification system based on taxonomy and protein 3D structure to identify 109 lectin classes. Hidden Markov Model (HMM) profiles for each class were used to search bacterial genomes, resulting in the prediction of >100 000 bacterial lectins available at unilectin.eu/bacteria. Genome screening of 90 isolates from 21 vaginal bacterial species showed that potential pathogens produce a larger variety of lectins than commensals indicating increased glycan-binding potential. Both the number of predicted bacterial lectins, and their specificities for carbohydrates correlated with pathogenicity. This study provides new insights into potential mechanisms of commensal and pathogen colonisation of the reproductive tract that underpin health and disease states.

bioinformatics↗

bioRxiv2020

Regulatory T cell activation triggers specific changes in glycosylation associated with Siglec-1-dependent inflammatory responses

Siglec-1 is a macrophage lectin-like receptor that mediates sialic acid-dependent cellular interactions. It was shown previously to promote inflammation in autoimmune disease through suppressing the expansion of regulatory T cells (Tregs). We have investigated the molecular basis for Siglec-1 binding to these cells using in vitro-induced Tregs. Siglec-1 binding was strongly upregulated on activated cells, but lost under resting conditions. Glycosylation changes that affect Siglec-1 binding were studied by comparing activated and resting Tregs using RNA-Seq, glycomics, proteomics and binding of selected antibodies and lectins. A proximity labelling and proteomics strategy identified 49 glycoproteins expressed by activated Tregs that may function as Siglec-1 counter-receptors. These represent [~]5% of the total membrane protein pool and were mainly related to T cell activation and proliferation. We demonstrate that several of these counter-receptors are upregulated following activation of Tregs and provide initial evidence that their altered glycosylation may also be important for Siglec-1 binding.

immunology↗

bioRxiv2020

Mitochondrial D-loop sequence variation and maternal lineage in the endangered Cleveland Bay horse

Genetic diversity and maternal ancestry line relationships amongst a sample of 96 Cleveland Bay horses were investigated using a 479bp length of mitochondrial D-loop sequence. The analysis yielded at total of 11 haplotypes with 27 variable positions, all of which have been described in previous equine mitochondrial DNA d-loop studies. Four main haplotype clusters were present in the Cleveland Bay breed describing 89% of the total sample. This suggests that only four principal maternal ancestry lines exist in the present-day global Cleveland Bay population. Comparison of these sequences with other domestic horse haplotypes shows a close association of the Cleveland Bay horse with Northern European (Clade C), Iberian (Clade A) and North African (Clade B) horse breeds. This indicates that the Cleveland Bay horse may not have evolved exclusively from the now extinct Chapman horse, as previous work as suggested. The Cleveland Bay horse remains one of only fivedomestic horse breeds classified as Critical on the Rare Breeds Survival Trust (UK) Watchlist and our results provide important information on the origins of this breed and represent a valuable tool for conservation purposes.

genetics↗

bioRxiv2020

Genetic Analysis of The Endangered Cleveland Bay Horse: A Century of Breeding Characterised by Pedigree and Microsatellite Data

The Cleveland Bay horse is one of the oldest equines in the United Kingdom, with pedigree data going back almost 300 years. The studbook is essentially closed and because of this, there are concerns about loss of genetic variation across generations. The breed is one of five equine breeds listed as "critical" (<300 registered adult breeding females) by the UK Rare Breeds Survival Trust in their annual Watchlist. Due to their critically endangered status, the current breadth of their genetic diversity is of concern, and assessment of this can lead to improved breed management strategies. Herein, both genealogical and molecular methods are combined in order to assess founder representation, lineage, and allelic diversity. Data from 16 microsatellite loci from a reference population of 402 individuals determined a loss of 91% and 48% of stallion and dam lines, respectively in the reference population. Only 3 ancestors determine 50% of the genome in the living population, with 70% of maternal lineage being derived from 3 founder females, and all paternal lineages traced back to a single founder stallion. Methods and theory are described in detail in order to demonstrate the scope of this analysis for wider conservation strategies. We quantitatively demonstrate the critical nature of the genetic resources within the breed, and offer a perspective on implementing this data in considered breed management strategies.

genetics↗

bioRxiv2020

Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in Rheumatoid Arthritis.

In healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis but are recognized to adopt a pathological role in rheumatoid arthritis (RA), promoting the infiltration and activation of immune cells to perpetuate local inflammation, pain and joint destruction. Carbohydrates (glycans) attached to cell surface proteins are fundamental regulators of cellular interactions between stromal and immune cells, but very little is known about the glycome of SFs or how glycosylation regulates their biology. Here we fill these gaps in our understanding of stromal guided pathophysiology by systematically mapping glycosylation pathways in healthy and arthritic SFs. We used a combination of transcriptomic and glycomic analysis to show that transformation of fibroblasts into pro-inflammatory cells in RA is associated with profound glycan remodeling, a process that involves reduction of 2-6 terminal sialylation that is mostly mediated by TNF-dependent inhibition of the glycosyltransferase ST6Gal1. We also show that sialylation of SFs correlates with distinct disease stages and SFs functional subsets in both human RA and models of mouse arthritis. We propose that pro-inflammatory cytokines in the joint remodel the SF-glycome, transforming a regulatory tissue intended to preserve local homeostasis, into an under-sialylated and highly pro-inflammatory microenvironment that contributes to an amplificatory inflammatory network that perpetuates chronic inflammation. These results highlight the importance of cell glycosylation in stromal immunology.

immunology↗

bioRxiv2019

Choice of host cell line is essential for the functional glycosylation of the fragment crystallizable (Fc) region of human IgG1 inhibitors of influenza B viruses

Antibodies are glycoproteins that carry a conserved N-linked carbohydrate attached to the Fc, whose presence and fine structure profoundly impacts on their in vivo immunogenicity, pharmacokinetics and functional attributes. The host cell line used to produce IgG has a major impact on this glycosylation, as different systems express different glycosylation enzymes and transporters that contribute to the specificity and heterogeneity of the final IgG-Fc glycosylation profile. Here we compare two panels of glycan-adapted IgG1-Fc mutants expressed in either the HEK 293-F or CHO-K1 systems. We show that the types of N-linked glycans between matched pairs of Fc mutants vary significantly, and in particular with respect to sialylation. These cell line effects on glycosylation profoundly influence the ability of the engineered Fcs to interact with either human or pathogen receptors. For example, we describe Fc mutants that potently disrupted influenza B-mediated agglutination of human erythrocytes when expressed in CHO-K1 but not in HEK 293-F cells.

immunology↗

bioRxiv2017

Collective animal navigation and migratory culture: from theoretical models to empirical evidence

Animals often travel in groups, and their navigational decisions can be influenced by social interactions. Both theory and empirical observations suggest that such collective navigation can result in individuals improving their ability to find their way and could be one of the key benefits of sociality for these species. Here we provide an overview of the potential mechanisms underlying collective navigation and review the known, and supposed, empirical evidence for such behaviour, and highlight interesting directions for future research. We further explore how both social and collective learning during group navigation could lead to the accumulation of knowledge at the population level, resulting in the emergence of migratory culture.

ecology↗