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  • Journal article
    Luo S, Li X-R, Gong X-T, Kulikovsky A, Qu F, Beis K, Severinov K, Dubiley S, Feng X, Dong S-H, Nair SKet al., 2025,

    Trojan horse peptide conjugates remodel the activity spectrum of clinical antibiotics.

    , Proc Natl Acad Sci U S A, Vol: 122

    Infections caused by gram-negative pathogens continue to be a major risk to human health because of the innate antibiotic resistance endowed by their unique cell membrane architecture. Nature has developed an elegant solution to target gram-negative strains, namely by conjugating toxic antibiotic warheads to a suitable carrier to facilitate the active import of the drug to a specific target organism. Microcin C7 (McC) is a Trojan horse peptide-conjugated antibiotic that specifically targets enterobacteria by exploiting active import through oligopeptide transport systems. Here, we characterize the molecular mechanism of McC recognition by YejA, the solute binding protein of the Escherichia coli oligopeptide transporter. Structure-guided mutational and functional analysis elucidates the determinants of substrate recognition. We demonstrate that the peptide carrier can serve as a passport for the entry of molecules that are otherwise not taken into E. coli cells. We show that peptide conjugation can remodel the antibiotic spectrum of clinically relevant parent compounds. Bioinformatics analysis reveals a broad distribution of YejA-like transporters in only the Proteobacteria, underscoring the potential for the development of Trojan horse antibiotics that are actively imported into such gram-negative bacteria.
  • Journal article
    Tolosana I, Willis K, Gribble M, Phillimore L, Burt A, Nolan T, Crisanti A, Bernardini Fet al., 2025,

    A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae.

    , Nat Commun, Vol: 16

    Genetic control - the deliberate introduction of genetic traits to control a pest or vector population - offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. To our knowledge, our system represents a pioneering approach in the engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to seven times more efficient for population suppression than optimal versions of other self-limiting strategies, such as the widely used Sterile Insect Technique or the Release of Insects carrying a Dominant Lethal gene.
  • Journal article
    Powell HR, Islam SA, David A, Sternberg MJEet al., 2025,

    Phyre2.2: A Community Resource for Template-based Protein Structure Prediction

    , Journal of Molecular Biology, ISSN: 0022-2836

    Template-based modelling, also known as homology modelling, is a powerful approach to predict the structure of a protein from its amino acid sequence. The approach requires one to identify a sequence similarity between the query sequence and that of a known structure as they will adopt a similar conformation, and the known structure can be used as the template for modelling the query sequence. Recently several approaches, most notably AlphaFold, have employed enhanced machine learning and have yielded accurate models irrespective of whether there is an identifiable template. Here we report Phyre2.2 which incorporates several enhancements to our widely-used template modelling portal Phyre2. The main development is facilitating a user to submit their sequence and then Phyre2.2 identifies the most suitable AlphaFold model to be used as a template. In Phyre2.2 the user searches a template library of known structures. We have now included in our library a representative structure for every protein sequence in the protein databank (PDB). In addition, there are representatives for an apo and a holo structure if they are in the PDB. The ranking of hits has been modified to highlight to the user if there are different domains spanning the sequence. Phyre2.2 continues to support batch processing where a user can submit up to 100 sequences facilitating processing of proteomes. Phyre2.2 is freely available to all users, including commercial users, at https://www.sbg.bio.ic.ac.uk/phyre2/.
  • Journal article
    Chan AHH, Putra P, Schupp H, Köchling J, Straßheim J, Renner B, Schroeder J, Pearse WD, Nakagawa S, Burke T, Griesser M, Meltzer A, Lubrano S, Kano Fet al., 2025,

    YOLO-Behaviour: A simple, flexible framework to automatically quantify animal behaviours from videos

    , Methods in Ecology and Evolution

    Manually coding behaviours from videos is essential to study animal behaviour but it is labour-intensive and susceptible to inter-rater bias and reliability issues. Recent developments of computer vision tools enable the automatic quantification of behaviours, supplementing or even replacing manual annotation. However, widespread adoption of these methods is still limited, due to the lack of annotated training datasets and domain-specific knowledge required to optimize these models for animal research. Here, we present YOLO-Behaviour, a flexible framework for identifying visually distinct behaviours from video recordings. The framework is robust, easy to implement, and requires minimal manual annotations as training data. We demonstrate the flexibility of the framework with case studies for event-wise detection in house sparrow nestling provisioning, Siberian jay feeding, human eating behaviours and frame-wise detections of various behaviours in pigeons, zebras and giraffes. Our results show that the framework reliably detects behaviours accurately and retrieve comparable accuracy metrics to manual annotation. However, metrics extracted for event-wise detection were less correlated with manual annotation, and potential reasons for the discrepancy between manual annotation and automatic detection are discussed. To mitigate this problem, the framework can be used as a hybrid approach of first detecting events using the pipeline and then manually confirming the detections, saving annotation time. We provide detailed documentation and guidelines on how to implement the YOLO-Behaviour framework, for researchers to readily train and deploy new models on their own study systems. We anticipate the framework can be another step towards lowering the barrier of entry for applying computer vision methods in animal behaviour.
  • Journal article
    Cheaib A, Waring EF, McNellis R, Perkowski EA, Martina JP, Seabloom EW, Borer ET, Wilfahrt PA, Dong N, Prentice IC, Wright IJ, Power SA, Hersch-Green EI, Risch AC, Caldeira MC, Nogueira C, Chen Q, Smith Net al., 2025,

    Soil nitrogen supply exerts largest influence on leaf nitrogen in environments with the greatest leaf nitrogen demand

    , Ecology Letters, Vol: 28, ISSN: 1461-023X

    Accurately representing the relationships between nitrogen supply and photosynthesis is crucial for reliably predicting carbon–nitrogen cycle coupling in Earth System Models (ESMs). Most ESMs assume positive correlations amongst soil nitrogen supply, leaf nitrogen content, and photosynthetic capacity. However, leaf photosynthetic nitrogen demand may influence the leaf nitrogen response to soil nitrogen supply; thus, responses to nitrogen supply are expected to be the largest in environments where demand is the greatest. Using a nutrient addition experiment replicated across 26 sites spanning four continents, we demonstrated that climate variables were stronger predictors of leaf nitrogen content than soil nutrient supply. Leaf nitrogen increased more strongly with soil nitrogen supply in regions with the highest theoretical leaf nitrogen demand, increasing more in colder and drier environments than warmer and wetter environments. Thus, leaf nitrogen responses to nitrogen supply are primarily influenced by climatic gradients in photosynthetic nitrogen demand, an insight that could improve ESM predictions.
  • Journal article
    Li H, Tang X, Yang T, Liao T, Debowski AW, Yang T, Shen Y, Nilsson H-O, Haslam SM, Mulloy B, Dell A, Stubbs KA, Fischer W, Haas R, Tang H, Marshall BJ, Benghezal Met al., 2025,

    Reinvestigation into the role of lipopolysaccharide Glycosyltransferases in pylori protein glycosylation

    , Gut Microbes, Vol: 17, ISSN: 1949-0976

    Protein glycosylation has been considered as a fundamental phenomenon shared by all domains of life. In Helicobacter pylori, glycosylation of flagellins A and B with pseudaminic acid have been rigorously confirmed and shown to be essential for flagella assembly and bacterial colonization. In addition to flagellins, several other proteins including RecA, AlpA/B, and BabA/B in H. pylori have also been reported to be glycosylated and to be dependent on the lipopolysaccharide (LPS) biosynthetic pathway. However, these proteins have not been purified for sugar-specific staining or structural analysis to confirm the existence of carbohydrate motifs. Here, using a combined approach of genetics, protein purification, and sugar-specific staining, we demonstrate that RecA is not a glycoprotein. Moreover, using LPS-protein reconstitution experiments, we demonstrate that the presence of O-antigen containing full-length LPS interferes with the electrophoretic mobility of H. pylori RecA and many other proteins including AlpA/B on SDS-PAGE. Finally, we demonstrate that full-length LPS extracted from E. coli affects electrophoretic migration of H. pylori proteins, while full-length LPS extracted from H. pylori similarly influences the electrophoretic migration of E. coli proteins. The impact is more subtle with E. coli LPS compared to H. pylori LPS, indicating that the magnitude of effect of LPS effects on protein mobility is dependent on bacterial source of the LPS. These findings suggest that the effects of full-length LPS on protein electrophoresis may represent a more general phenomenon. As LPS is a unique component of virtually all Gram-negative bacteria, our data suggest that when observing protein electrophoretic mobility shifts between wild-type and LPS mutant strains or between subcellular fractionation samples, the influence of LPS on protein electrophoretic migration should be considered first, rather than interpreting it as potential protein glycosylation that is depend
  • Book chapter
    Bolan N, Srinivasarao C, Rocco C, Bolan S, Mansoor S, Wani OA, Ahmad P, Weiss D, Northover G, Sánchez-Palacios JT, Cheng M, Bell R, Kumar GR, Naidu GM, Hou D, Jia X, Xie Y, Wang H, Antoniadis V, Melo TM, Shaheen SM, Rinklebe J, Kirkham MB, Siddique KHMet al., 2025,

    Zinc in soil-crop-animal-human health continuum

    , Advances in Agronomy, Pages: 1-61

    Globally, zinc (Zn) deficiency in soils, and subsequently crops, has emerged as one of the most prevalent among micronutrients, resulting in a severe decline in crop yields and nutritional quality and in adversely affecting animal and human health. Worldwide, more than half of the agricultural soils are inherently deficient in Zn, and the health of about one-third of the global human population is impacted by Zn deficiency. Zinc is an essential micronutrient for animal and human health, and, in the developing world, Zn deficiency has been identified as the fifth cause of disease and death for humans. The World Health Organization (WHO) reports that annually more than 800,000 people, including around 450,000 children under the age of 5, die due to Zn deficiency. Zinc supplementation was frequently associated with boosting immunity against COVID-19 in recent years. Because most of the Zn in animals and humans is derived from soil-grown crops, their source of Zn is highly dependent on plant Zn, especially in crops or fodder; in turn, crop Zn is dependent on available soil Zn levels. This integrated review describes Zn distribution, behavior, and fate in soils and its uptake and role in plants and crop production, as well as in the well-being of animals and humans. It discusses recent findings concerning Zn deficiency in all steps of the human food chain (from soil, to crop, animal, and human), and how it can be addressed through novel Zn fertilizers, soil amendments, and biofortification of Zn.
  • Journal article
    Zhong Z, Hocking B, Brown C, Ma T, White A, Mann D, Armstrong A, Bull Jet al., 2025,

    Synthesis and functionalization of sulfoximine-bicyclo[1.1.0]butanes: functionalizable, tuneable and cysteine-selective chiral warheads

    , Angewandte Chemie International Edition, Vol: 64, ISSN: 1433-7851

    Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.0]butanes (BCBs) as novel thiol reactive chiral warheads, achieved in one-pot from methylsulfoximines. Unusually the warhead can then be derivatized, keeping the BCB intact, over 3 vectors: i) sulfoximine N-modification instills a broad range of strain-release reactivity; ii) sp2-cross-coupling reactions on aryl-BCB-sulfoximines allows direct diversification, and iii) functionalization of the BCB motif itself is achieved by metalation and trapping with electrophiles. The BCB sulfoximines are shown to react selectively with cysteine including in a protein model (CDK2) under biocompatible conditions. Preliminary data indicate suitability for chemoproteomic applications, and enantioselective cysteine-labelling. The reactivity of sulfoximine BCBs with electron withdrawing groups on nitrogen is comparable to acrylamides with low to moderate reactivity.
  • Journal article
    Pickering G, O'Keeffe M, Bannister K, Becker S, Cottom S, Cox FJ, Eisenberg E, Finn DP, Forget P, GravenNielsen T, Kalso E, KocotKepska M, LeiteAlmeida H, LopezGarcia JA, Meeus M, Mouraux A, Pereira B, Puljak L, Reneman MF, Rohde I, Sotiropoulos I, Skidmore N, Tölle TR, Todorovic ST, Truini A, Vowles KE, PogatzkiZahn E, GarciaLarrea L, Fullen BMet al., 2025,

    A pain research strategy for Europe: A European survey and position paper of the European Pain Federation <scp>EFIC</scp>

    , European Journal of Pain, Vol: 29, ISSN: 1090-3801

    <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce ‘research waste’, improve the effectiveness of pain research and therapy and promote the uptake of research evidence. In this study, the European Pain Federation (EFIC) developed a Pain Research Strategy for Europe.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The study used multiple methods, including literature searches, multidisciplinary expert debate, a survey and a final consensus meeting. The cross‐sectional survey was conducted among 628 European pain researchers, clinicians, educators and industry professionals to obtain the rating and hierarchy of pain research priorities.</jats:p><jats:p>The final consensus meeting involved a multidisciplinary expert panel including people with lived experience from 23 countries. The survey results guided discussions where top priorities were agreed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Content analysis identified nine survey themes, of which five emerged as top priorities: (i) understand the pathophysiology of pain; (ii) understand and address comorbidities; (iii) critically assess current therapies; (iv) develop new treatments; and (v) explore the biopsychosocial impacts of pain. Physical, psychological and social approaches were prioritized at the same level as pharmacological treatments. The top priorities were endorsed by a multidisciplinary expert panel. The panel emphasized the importance of also clearly communicating the con
  • Journal article
    Stocker B, Dong N, Perkowski EA, Schneider PD, Xu H, de Boer H, Rebel KT, Smith NG, Van Sundert K, Wang H, Jones SE, Prentice IC, Harrison SPet al., 2025,

    Empirical evidence and theoretical understanding ofecosystem carbon and nitrogen cycle interactions

    , New Phytologist, Vol: 245, Pages: 49-68, ISSN: 0028-646X

    Interactions between carbon (C) and nitrogen (N) cycles in terrestrial ecosystems are simulated in advanced vegetation models, yet methodologies vary widely, leading to divergent simulations of past land C balance trends. This underscores the need to reassess our understanding of ecosystem processes, given recent theoretical advancements and empirical data. We review current knowledge, emphasising evidence from experiments and trait data compilations for vegetation responses to CO2 and N input, alongside theoretical and ecological principles for modelling. N fertilisation increases leaf N content but inconsistently enhances leaf-level photosynthetic capacity. Whole-plant responses include increased leaf area and biomass, with reduced root allocation and increased aboveground biomass. Elevated atmospheric CO2 also boosts leaf area and biomass but intensifies belowground allocation, depleting soil N and likely reducing N losses. Global leaf traits data confirm these findings, indicating that soil N availability influences leaf N content more than photosynthetic capacity. A demonstration model based on the functional balance hypothesis accurately predicts responses to N and CO2 fertilisation on tissue allocation, growth and biomass, offering a path to reduce uncertainty in global C cycle projections.
  • Journal article
    Lyons-White J, Zodua PA, Yobo CM, Carlon SC, Ewers RM, Knight ATet al., 2025,

    Challenges for implementing zero deforestation commitments in a highly forested country: Perspectives from Liberia's palm oil sector

    , WORLD DEVELOPMENT, Vol: 185, ISSN: 0305-750X
  • Journal article
    Reen V, D'Ambrosio M, Søgaard PP, Tyson K, Leeke BJ, Clément I, Dye ICA, Pombo J, Kuba A, Lan Y, Burr J, Bomann IC, Kalyva M, Birch J, Khadayate S, Young G, Provencher D, Mes-Masson A-M, Vernia S, McGranahan N, Brady HJM, Rodier F, Nativio R, Percharde M, McNeish IA, Gil Jet al., 2025,

    SMARCA4 regulates the NK-mediated killing of senescent cells

    , Science Advances, Vol: 11, ISSN: 2375-2548

    Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells. We identified that genetic or pharmacological inhibition of SMARCA4 enhanced senescent cell elimination by NK cells. SMARCA4 expression is elevated during senescence and its inhibition derepresses repetitive elements, inducing the SASP via activation of cGAS/STING and MAVS/MDA5 pathways. Moreover, a PROTAC targeting SMARCA4 synergized with cisplatin to increase the infiltration of CD8 T cells and mature, activated NK cells in an immunocompetent model of ovarian cancer. Our results indicate that SMARCA4 inhibitors enhance NK-mediated surveillance of senescent cells and may represent senotherapeutic interventions for ovarian cancer.
  • Book chapter
    Dey S, Majumdar A, Dubey PK, Roychowdhury T, Majumdar J, Santra SC, Hossain A, Moulick Det al., 2025,

    Involvement of soil parameters and rhizosphere microbiome in sustainable crop productivity

    , Rhizomicrobiome in Sustainable Agriculture and Environment, Publisher: Elsevier, Pages: 189-228, ISBN: 9780443236914
  • Book chapter
    McArthur HCW, Bajur AT, Spillane KM, 2025,

    Quantifying force-mediated antigen extraction in the B cell immune synapse using DNA-based tension sensors.

    , Pages: 99-126

    B cells exert pulling forces against antigen-presenting cells (APCs) to extract antigens for internalization. The application of tugging forces on B cell receptor (BCR)-antigen bonds promotes discrimination of antigen affinities and sensing of APC physical properties. Here, we describe a protocol for preparing antigen-functionalized DNA tension sensors for quantifying force-mediated antigen extraction in the B cell immune synapse. We describe how to attach the sensors to planar lipid bilayers, quantify their surface density, use them to stimulate B cell activation, and analyze the efficiency of antigen extraction in fixed cells by fluorescence microscopy and image analysis. These techniques should be broadly applicable to studies of force-mediated transfer of molecules in cell-cell contacts.
  • Book chapter
    Majumdar J, Biswas JK, Majumdar A, Roychowdhury T, Santra SC, Hossain A, Moulick Det al., 2025,

    Rhizomicrobiome: Role in management of heavy metal stress in plants

    , Rhizomicrobiome in Sustainable Agriculture and Environment, Publisher: Elsevier, Pages: 315-332, ISBN: 9780443236914
  • Journal article
    Tong Jia Ming S, Tan Yi Jun K, Carissimo G, 2024,

    Pathogenicity and virulence of O’nyong-nyong virus: A less studied <i>Togaviridae</i> with pandemic potential

    , Virulence, Vol: 15, ISSN: 2150-5594
  • Journal article
    Abitbol V, Martinon-Torres F, Taha M-K, Nolan T, Muzzi A, Bambini S, Borrow R, Toneatto D, Serino L, Rappuoli R, Pizza Met al., 2024,

    4CMenB journey to the 10-year anniversary and beyond

    , HUMAN VACCINES & IMMUNOTHERAPEUTICS, Vol: 20, ISSN: 2164-5515
  • Journal article
    Efron A, Brozzi A, Biolchi A, Bodini M, Giuliani M, Guidotti S, Lorenzo F, Moscoloni MA, Muzzi A, Nocita F, Pizza M, Rappuoli R, Tomei S, Vidal G, Vizzotti C, Campos J, Sorhouet Pereira Cet al., 2024,

    Genetic characterization and estimated 4CMenB vaccine strain coverage of 284 <i>Neisseria meningitidis</i> isolates causing invasive meningococcal disease in Argentina in 2010-2014

    , HUMAN VACCINES & IMMUNOTHERAPEUTICS, Vol: 20, ISSN: 2164-5515
  • Journal article
    Dias Fernandes L, Hintzen R, Thompson S, Barychka T, Tittensor D, Harfoot M, Newbold T, Rosindell Jet al., 2024,

    Species Richness and Speciation Rates for all Terrestrial Animals Emerge from a Synthesis of Ecological Theories

    , Systematic Biology, ISSN: 1063-5157
  • Journal article
    Allgöwer F, Pöverlein MC, Rutherford AW, Kaila VRIet al., 2024,

    Mechanism of proton release during water oxidation in Photosystem II.

    , Proc Natl Acad Sci U S A, Vol: 121

    Photosystem II (PSII) catalyzes light-driven water oxidation that releases dioxygen into our atmosphere and provides the electrons needed for the synthesis of biomass. The catalysis occurs in the oxygen-evolving oxo-manganese-calcium (Mn4O5Ca) cluster that drives the oxidation and deprotonation of substrate water molecules leading to the O2 formation. However, despite recent advances, the mechanism of these reactions remains unclear and much debated. Here, we show that the light-driven Tyr161D1 (Yz) oxidation adjacent to the Mn4O5Ca cluster, decreases the barrier for proton transfer from the putative substrate water molecule (W3/Wx) to Glu310D2, accessible to the luminal bulk. By combining hybrid quantum/classical (QM/MM) free energy calculations with atomistic molecular dynamics simulations, we probe the energetics of the proton transfer along the Cl1 pathway. We demonstrate that the proton transfer occurs via water molecules and a cluster of conserved carboxylates, driven by redox-triggered electric fields directed along the pathway. Glu65D1 establishes a local molecular gate that controls the proton transfer to the luminal bulk, while Glu312D2 acts as a local proton storage site. The identified gating region could be important in preventing backflow of protons to the Mn4O5Ca cluster. The structural changes, derived here based on the dark-state PSII structure, strongly support recent time-resolved X-ray free electron laser data of the S3 → S4 transition (Bhowmick et al. Nature 617, 2023) and reveal the mechanistic basis underlying deprotonation of the substrate water molecules. Our findings provide insight into the water oxidation mechanism of PSII and show how the interplay between redox-triggered electric fields, ion-pairs, and hydration effects control proton transport reactions.
  • Journal article
    Tica J, Oliver Huidobro M, Zhu T, Wachter G, Pazuki R, Bazzoli D, Scholes N, Tonello E, Siebert H, Stumpf M, Endres R, Isalan Met al., 2024,

    A three-node Turing gene circuit forms periodic spatial patterns in bacteria

    , Cell Systems, Vol: 15, Pages: 1123-1132.e3, ISSN: 2405-4720

    Turing patterns are self-organizing systems that can form spots, stripes, or labyrinths. Proposed examples in tissue organization include zebrafish pigmentation, digit spacing, and many others. The theory of Turing patterns in biology has been debated because of their stringent fine-tuning requirements, where patterns only occur within a small subset of parameters. This has complicated the engineering of synthetic Turing gene circuits from first principles, although natural genetic Turing networks have been identified. Here, we engineered a synthetic genetic reaction-diffusion system where three nodes interact according to a non-classical Turing network with improved parametric robustness. The system reproducibly generated stationary, periodic, concentric stripe patterns in growing E. coli colonies. A partial differential equation model reproduced the patterns, with a Turing parameter regime obtained by fitting to experimental data. Our synthetic Turing system can contribute to nanotechnologies, such as patterned biomaterial deposition, and provide insights into developmental patterning programs. A record of this paper’s transparent peer review process is included in the supplemental information.
  • Journal article
    Flintham E, Savolainen V, Otto S, Reuter M, Mullon Cet al., 2024,

    The maintenance of genetic polymorphism underlyingsexually antagonistic traits

    , Evolution Letters, ISSN: 2056-3744

    Selection often favours different trait values in males and females, leading to genetic conflicts between the sexes when traits have a shared genetic basis. Such sexual antagonism has beenproposed to maintain genetic polymorphism. However, this notion is based on insights from population genetic models of single loci with fixed fitness effects. It is thus unclear how readily polymorphism emerges from sex-specific selection acting on continuous traits, where fitness effects arisefrom the genotype-phenotype map and the fitness landscape. Here we model the evolution of a continuous trait that has a shared genetic basis but different optima in males and females, considering a wide variety of genetic architectures and fitness landscapes. For autosomal loci, the long-termmaintenance of polymorphism requires strong conflict between males and females that generatesuncharacteristic sex-specific fitness patterns. Instead, more plausible sex-specific fitness landscapestypically generate stabilising selection leading to an evolutionarily stable state that consists of a singlehomozygous genotype. Except for sites tightly linked to the sex determining region, our results indicate that genetic variation due to sexual antagonism should arise only rarely and often be transient,making these signatures challenging to detect in genomic data.
  • Journal article
    Sethi SS, Bick A, Chen M-Y, Crouzeilles R, Hillier BV, Lawson J, Lee C-Y, Liu S-H, Parruco CHDF, Rosten CM, Somveille M, Tuanmu M-N, Banks-Leite Cet al., 2024,

    Reply to Araújo: Good science requires focus.

    , Proc Natl Acad Sci U S A, Vol: 121
  • Journal article
    Cohen EJ, Drobnič T, Ribardo DA, Yoshioka A, Umrekar T, Guo X, Fernandez J-J, Brock EE, Wilson L, Nakane D, Hendrixson DR, Beeby Met al., 2024,

    Evolution of a large periplasmic disk in Campylobacterota flagella enables both efficient motility and autoagglutination.

    , Dev Cell, Vol: 59, Pages: 3306-3321.e5

    The flagellar motors of Campylobacter jejuni (C. jejuni) and related Campylobacterota (previously epsilonproteobacteria) feature 100-nm-wide periplasmic "basal disks" that have been implicated in scaffolding a wider ring of additional motor proteins to increase torque, but the size of these disks is excessive for a role solely in scaffolding motor proteins. Here, we show that the basal disk is a flange that braces the flagellar motor during disentanglement of its flagellar filament from interactions with the cell body and other filaments. We show that motor output is unaffected when we shrink or displace the basal disk, and suppressor mutations of debilitated motors occur in flagellar-filament or cell-surface glycosylation pathways, thus sidestepping the need for a flange to overcome the interactions between two flagellar filaments and between flagellar filaments and the cell body. Our results identify unanticipated co-dependencies in the evolution of flagellar motor structure and cell-surface properties in the Campylobacterota.
  • Journal article
    Ono M, Crompton T, 2024,

    A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.

    , Development, Vol: 151

    Progenitor cells initiate development upon receiving key signals, dynamically altering gene and protein expression to diverge into various lineages and fates. Despite the use of several experimental approaches, including the Fluorescent Timer-based method Timer-of-cell-kinetics-and-activity (Tocky), analysing time-dependent processes at the single-cell level in vivo remains challenging. This study introduces a novel integrated experimental and computational approach, using an advanced multidimensional toolkit. This toolkit facilitates the simultaneous examination of temporal progression and T-cell profiles using high-dimensional flow cytometric data. Employing novel algorithms based on canonical correspondence analysis and network analysis, our toolkit identifies developmental trajectories and analyses dynamic changes in developing cells. The efficacy of this approach is demonstrated by analysing thymic T cells from Nr4a3-Tocky mice, which monitor activities downstream of the T-cell receptor (TCR) signal. Further validation was achieved by deleting the proapoptotic gene Bcl2l11 in Nr4a3-Tocky mice. This revealed dynamic changes in thymic T cells during cellular development and negative selection following TCR signalling. Overall, this study establishes a new method for analysing the temporal dynamics of individual developing cells in response to in vivo signalling cues.
  • Journal article
    King OG, Horrocks V, Yip AYG, McDonald JAKet al., 2024,

    Next-generation microbiome therapeutics: why it is important to consider the space left in the wake of antibiotic treatment

    , FUTURE MICROBIOLOGY, Vol: 19, Pages: 1515-1518, ISSN: 1746-0913
  • Journal article
    Copland A, Mackie GM, Scarfe L, Jinks E, Lecky DAJ, Gudgeon N, McQuade R, Ono M, Barthel M, Hardt W-D, Ohno H, Hoevenaar WHM, Dimeloe S, Bending D, Maslowski KMet al., 2024,

    <i>Salmonella</i> cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity

    , EMBO MOLECULAR MEDICINE, Vol: 16, Pages: 3057-3088, ISSN: 1757-4676
  • Journal article
    Roberts C, Bird K, Chrismas N, Hartman S, Cunliffe Met al., 2024,

    Depth-dependent bacterial colonization on model chitin particles in the open ocean

    , LETTERS IN APPLIED MICROBIOLOGY, Vol: 77, ISSN: 0266-8254
  • Journal article
    Rowell J, Lau C-I, Ross S, Yanez DC, Peña OA, Chain B, Crompton Tet al., 2024,

    Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus.

    , Elife, Vol: 13

    Here, we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8- single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3'TRAV and 5'TRAJ rearrangements in all populations, whereas adult repertoires used more 5'TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3'TRAV and 5'TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire. The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.
  • Journal article
    Le Penru NP, Heath BE, Dunning J, Picinali L, Ewers RM, Sethi SSet al., 2024,

    Towards using virtual acoustics for evaluating spatial ecoacoustic monitoring technologies

    , METHODS IN ECOLOGY AND EVOLUTION, ISSN: 2041-210X

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