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  • Journal article
    Endres R, Cavanagh H, Mosbach A, Scalliet G, Lind Ret al., 6424,

    Physics-informed deep learning characterizes morphodynamics of Asian soybean rust disease

    , Nature Communications, Vol: 12, Pages: 1-8, ISSN: 2041-1723

    Medicines and agricultural biocides are often discovered using large phenotypic screens across hundreds of compounds, where visible effects of whole organisms are compared to gauge efficacy and possible modes of action. However, such analysis is often limited to human-defined and static features. Here, we introduce a novel framework that can characterize shape changes (morphodynamics) for cell-drug interactions directly from images, and use it to interpret perturbed development of Phakopsora pachyrhizi, the Asian soybean rust crop pathogen. We describe population development over a 2D space of shapes (morphospace) using two models with condition-dependent parameters: a top-down Fokker-Planck model of diffusive development over Waddington-type landscapes, and a bottom-up model of tip growth. We discover a variety of landscapes, describing phenotype transitions during growth, and identify possible perturbations in the tip growth machinery that cause this variation. This demonstrates a widely-applicable integration of unsupervised learning and biophysical modeling.

  • Journal article
    Kirwan GM, Broughton RK, Lees AC, Ottenburghs J, Tobias JAet al., 2022,

    The ‘Meidum geese’ revisited: Early historical art is not a suitable basis for taxonomic speculation

    , Journal of Archaeological Science: Reports, Vol: 41, ISSN: 2352-409X

    Romilio (2021) used a taxonomic scoring system to compare differences between three species of geese (Anseriformes) depicted in the Chapel of Itet, one of which he speculated might represent an undescribed (presumably now extinct) species. Despite some apparently distinctive features, the depiction has traditionally been associated with the well-known modern species, red-breasted goose (Branta ruficollis). We discuss limitations in applying the Tobias et al. (2010) scoring system to cases such as this, for which it was not designed, and we outline the many pitfalls that must be considered when attempting to identify historical artwork of birds using examples discussed recently in the ornithological literature. We conclude that the illustrations proposed by Romilio to represent a new Branta goose species are within the range of known plumage variation and potential artistic licence for red-breasted goose, and that this very probably is the species upon which the artwork was based. More generally, we caution against applying the Tobias criteria to cases where a series of specimens cannot be measured, and highlight the difficulties of using illustrations to inform taxonomy.

  • Journal article
    Chen C, Riley W, Prentice IC, Keenan Tet al., 2022,

    CO2 fertilization of terrestrial photosynthesis inferred from site to global scales.

    , Proceedings of the National Academy of Sciences of USA, ISSN: 0027-8424
  • Journal article
    Matthews S, 2022,

    Secondary structure and X-ray crystallographic analysis of the Glideosome-Associated Connector (GAC) from Toxoplasma gondii

    , Crystals, ISSN: 2073-4352
  • Journal article
    Anthony MA, Crowther TW, van der Linde S, Suz LM, Bidartondo MI, Cox F, Schaub M, Rautio P, Ferretti M, Vesterdal L, De Vos B, Dettwiler M, Eickenscheidt N, Schmitz A, Meesenburg H, Andreae H, Jacob F, Dietrich H-P, Waldner P, Gessler A, Frey B, Schramm O, van den Bulk P, Hensen A, Averill Cet al., 2022,

    Forest tree growth is linked to mycorrhizal fungal composition and function across Europe

    , The ISME Journal: multidisciplinary journal of microbial ecology, ISSN: 1751-7362

    Most trees form symbioses with ectomycorrhizal fungi (EMF) which influence access to growth-limiting soil resources. Mesocosm experiments repeatedly show that EMF species differentially affect plant development, yet whether these effects ripple up to influence the growth of entire forests remains unknown. Here we tested the effects of EMF composition and functional genes relative to variation in well-known drivers of tree growth by combining paired molecular EMF surveys with high-resolution forest inventory data across 15 European countries. We show that EMF composition was linked to a three-fold difference in tree growth rate even when controlling for the primary abiotic drivers of tree growth. Fast tree growth was associated with EMF communities harboring high inorganic but low organic nitrogen acquisition gene proportions and EMF which form contact versus medium-distance fringe exploration types. These findings suggest that EMF composition is a strong bio-indicator of underlying drivers of tree growth and/or that variation of forest EMF communities causes differences in tree growth. While it may be too early to assign causality or directionality, our study is one of the first to link fine-scale variation within a key component of the forest microbiome to ecosystem functioning at a continental scale.

  • Journal article
    Amos B, Aurrecoechea C, Barba M, Barreto A, Basenko EY, Bażant W, Belnap R, Blevins AS, Böhme U, Brestelli J, Brunk BP, Caddick M, Callan D, Campbell L, Christensen MB, Christophides GK, Crouch K, Davis K, DeBarry J, Doherty R, Duan Y, Dunn M, Falke D, Fisher S, Flicek P, Fox B, Gajria B, Giraldo-Calderón GI, Harb OS, Harper E, Hertz-Fowler C, Hickman MJ, Howington C, Hu S, Humphrey J, Iodice J, Jones A, Judkins J, Kelly SA, Kissinger JC, Kwon DK, Lamoureux K, Lawson D, Li W, Lies K, Lodha D, Long J, MacCallum RM, Maslen G, McDowell MA, Nabrzyski J, Roos DS, Rund SSC, Schulman SW, Shanmugasundram A, Sitnik V, Spruill D, Starns D, Stoeckert CJ, Tomko SS, Wang H, Warrenfeltz S, Wieck R, Wilkinson PA, Xu L, Zheng Jet al., 2022,

    VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center.

    , Nucleic Acids Res, Vol: 50, Pages: D898-D911

    The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC.

  • Journal article
    Knoppová J, Sobotka R, Yu J, Bečková M, Pilný J, Trinugroho JP, Csefalvay L, Bína D, Nixon PJ, Komenda Jet al., 2022,

    Assembly of D1/D2 reaction center complexes of photosystem II: binding of pigments and a network of auxiliary proteins

    , Plant Physiology, ISSN: 0032-0889
  • Journal article
    Janssens J, Aibar S, Taskiran II, Ismail JN, Gomez AE, Aughey G, Spanier K, De Rop F, Gonzalez-Blas CB, Dionne M, Grimes K, Quan XJ, Papasokrati D, Hulselmans G, Makhzami S, De Waegeneer M, Christiaens V, Southall T, Aerts Set al., 2022,

    Decoding gene regulation in the fly brain

    , NATURE, ISSN: 0028-0836
  • Journal article
    Mullineaux Sanders C, Kozik Z, Sanchez Garrido J, Hopkins EGD, Choudhary JS, Frankel Get al., 2022,

    Citrobacter rodentium infection induces persistent molecular changes and IFNg-dependant MHC class II expression in the colonic epithelium

    , mBio, ISSN: 2150-7511
  • Journal article
    Peswani AR, Narkpuk J, Krueger A, Bracewell DG, Lekcharoensuk P, Haslam SM, Dell A, Jaru-Ampornpan P, Robinson Cet al., 2022,

    Novel constructs and 1-step chromatography protocols for the production of Porcine Circovirus 2d (PCV2d) and Circovirus 3 (PCV3) subunit vaccine candidates

    , FOOD AND BIOPRODUCTS PROCESSING, Vol: 131, Pages: 125-135, ISSN: 0960-3085
  • Journal article
    Lyons-White J, Mikolo Yobo C, Ewers RM, Knight ATet al., 2022,

    Understanding zero deforestation and the High Carbon Stock Approach in a highly forested tropical country

    , Land Use Policy, Vol: 112, Pages: 1-12, ISSN: 0264-8377

    “Zero deforestation” commitments are pledges by companies to avoid deforestation when producing palm oil. Zero deforestation can be implemented using the High Carbon Stock Approach (HCSA), a tool that distinguishes forests from degraded land which can be developed. In highly forested countries like Gabon, zero deforestation may conflict with national economic goals involving palm oil and other agricultural commodities. We investigated perspectives of stakeholders in Gabon about zero deforestation and the HCSA using Critical Systems Heuristics, a systems thinking methodology. In 25 interviews with government, NGOs, companies, and research institutions, and two focus groups with rural communities, we identified three contrasting perspectives on forest conservation and agro industrial development: international, national, and local. Zero deforestation represents an international perspective that marginalises issues from a national perspective. This may produce unintended consequences that undermine the legitimacy of zero deforestation, including conversion of Gabon’s savannahs and disincentives for sustainable business. From a local perspective, zero deforestation is embedded in an agro-industrial vision that may marginalise value judgments concerning forests and traditional livelihoods. Gabon’s National Land Use Plan could help reconcile the three perspectives but requires recognition by international standards. Adapting the HCSA to Gabon’s context should also be considered to promote legitimacy. Research is required to ensure proposed institutional arrangements deliver equitable multi-stakeholder participation in land-use planning. Gabon’s case shows the applicability of zero deforestation to all highly forested countries cannot be assumed. Improved international understanding of national contexts, and flexibility in applying “zero deforestation”, is important for designing effective and equitable international standard

  • Journal article
    Lavergne A, Hemming D, Prentice IC, Guerrieri R, Oliver R, Graven Het al., 2022,

    Global decadal variability of plant carbon isotope discrimination and its link to gross primary production.

    , Global Change Biology, Vol: 28, Pages: 524-541, ISSN: 1354-1013

    Carbon isotope discrimination (Δ13C) in C3 woody plants is a key variable for the study of photosynthesis. Yet how Δ13C varies at decadal scales, and across regions, and how it is related to gross primary production (GPP), are still incompletely understood. Here we address these questions by implementing a new Δ13C modelling capability in the land-surface model JULES incorporating both photorespiratory and mesophyll-conductance fractionations. We test the ability of four leaf-internal CO2 concentration models embedded in JULES to reproduce leaf and tree-ring (TR) carbon isotopic data. We show that all the tested models tend to overestimate average Δ13C values, and to underestimate interannual variability in Δ13C. This is likely because they ignore the effects of soil water stress on stomatal behavior. Variations in post-photosynthetic isotopic fractionations across species, sites and years, may also partly explain the discrepancies between predicted and TR-derived Δ13C values. Nonetheless, the “least-cost” (Prentice) model shows the lowest biases with the isotopic measurements, and lead to improved predictions of canopy-level carbon and water fluxes. Overall, modelled Δ13C trends vary strongly between regions during the recent (1979–2016) historical period but stay nearly constant when averaged over the globe. Photorespiratory and mesophyll effects modulate the simulated global Δ13C trend by 0.0015 ± 0.005‰ and –0.0006 ± 0.001‰ ppm−1, respectively. These predictions contrast with previous findings based on atmospheric carbon isotope measurements. Predicted Δ13C and GPP tend to be negatively correlated in wet-humid and cold regions, and in tropical African forests, but positively related elsewhere. The negative correlation between Δ13C and GPP is partly due to the strong dominant influences of temperature on GPP and vapor pressure deficit on Δ13

  • Journal article
    Kotidis P, Marbiah M, Donini R, Gómez IA, Del Val IJ, Haslam SM, Polizzi KM, Kontoravdi Cet al., 2022,

    Rapid Antibody Glycoengineering in CHO Cells Via RNA Interference and CGE-LIF N-Glycomics.

    , Methods Mol Biol, Vol: 2370, Pages: 147-167

    The impact of the glycan distribution on the in vivo function and half-life of monoclonal antibodies has long motivated the genetic engineering of producer cells to achieve structures that enhance efficacy, safety and stability. To facilitate glycoengineering of IgG-producing Chinese hamster ovary cells, we present a rapid protocol that involves the use of RNA interference for the knockdown of genes of interest coupled with capillary gel electrophoresis and laser-induced fluorescence detection (CGE-LIF) for fast, high-throughput glycan analysis. We apply this methodology to the Fut8 gene, responsible for the addition of core fucose, which is a typical target for increasing antibody-dependent cellular cytotoxicity.

  • Journal article
    Banks AM, Whitfield CJ, Brown SR, Fulton DA, Goodchild SA, Grant C, Love J, Lendrem DW, Fieldsend JE, Howard TPet al., 2022,

    Key reaction components affect the kinetics and performance robustness of cell-free protein synthesis reactions

    , Computational and Structural Biotechnology Journal, Vol: 20, Pages: 218-229, ISSN: 2001-0370
  • Journal article
    Lembrechts JJ, van den Hoogen J, Aalto J, Ashcroft MB, De Frenne P, Kemppinen J, Kopecký M, Luoto M, Maclean IMD, Crowther TW, Bailey JJ, Haesen S, Klinges DH, Niittynen P, Scheffers BR, Van Meerbeek K, Aartsma P, Abdalaze O, Abedi M, Aerts R, Ahmadian N, Ahrends A, Alatalo JM, Alexander JM, Nina Allonsius C, Altman J, Ammann C, Andres C, Andrews C, Ardö J, Arriga N, Arzac A, Aschero V, Assis RL, Johann Assmann J, Bader MY, Bahalkeh K, Barančok P, Barrio IC, Barros A, Barthel M, Basham EW, Bauters M, Bazzichetto M, Belelli Marchesini L, Bell MC, Benavides JC, Luis Benito Alonso J, Berauer BJ, Bjerke JW, Björk RG, Björkman MP, Björnsdóttir K, Blonder B, Boeckx P, Boike J, Bokhorst S, Brum BNS, Brůna J, Buchmann N, Buysse P, Luís Camargo J, Campoe OC, Candan O, Canessa R, Cannone N, Carbognani M, Carnicer J, Casanova-Katny A, Cesarz S, Chojnicki B, Choler P, Chown SL, Cifuentes EF, Čiliak M, Contador T, Convey P, Cooper EJ, Cremonese E, Curasi SR, Curtis R, Cutini M, Johan Dahlberg C, Daskalova GN, Angel de Pablo M, Della Chiesa S, Dengler J, Deronde B, Descombes P, Di Cecco V, Di Musciano M, Dick J, Dimarco RD, Dolezal J, Dorrepaal E, Dušek J, Eisenhauer N, Eklundh L, Erickson TE, Erschbamer B, Eugster W, Ewers RM, Exton DA, Fanin N, Fazlioglu F, Feigenwinter I, Fenu G, Ferlian O, Rosa Fernández Calzado M, Fernández-Pascual E, Finckh M, Finger Higgens R, Forte TGW, Freeman EC, Frei ER, Fuentes-Lillo E, García RA, García MB, Géron C, Gharun M, Ghosn D, Gigauri K, Gobin A, Goded I, Goeckede M, Gottschall F, Goulding K, Govaert S, Jessen Graae B, Greenwood S, Greiser C, Grelle A, Guénard B, Guglielmin M, Guillemot J, Haase P, Haider S, Halbritter AH, Hamid M, Hammerle A, Hampe A, Haugum SV, Hederová L, Heinesch B, Helfter C, Hepenstrick D, Herberich M, Herbst M, Hermanutz L, Hik DS, Hoffrén R, Homeier J, Hörtnagl L, Høye TT, Hrbacek F, Hylander K, Iwata H, Antoni Jackowicz-Korczynski M, Jactel H, Järveoja J, Jastrzębowski S, Jentsch A, Jiménez JJ, Jónsdóttir IS, Juckeret al., 2021,

    Global maps of soil temperature.

    , Glob Chang Biol

    Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological ap

  • Journal article
    Rutherford A, 2021,

    Bicarbonate-controlled reduction of oxygen by the QA semiquinone in Photosystem II in membranes

    , Proceedings of the National Academy of Sciences of USA, ISSN: 0027-8424
  • Journal article
    Zhong Q, Chatterjee S, Choudhary JS, Frankel Get al., 2021,

    EPEC-induced activation of the Ca2+ transporter TRPV2 leads to pyroptotic cell death

    , MOLECULAR MICROBIOLOGY, ISSN: 0950-382X
  • Journal article
    Giannos P, Kechagias K, 2021,

    SPP1 in infliximab resistant ulcerative colitis and associated colorectal cancer: an analysis of differentially expressed genes

    , European Journal of Gastroenterology and Hepatology, ISSN: 0954-691X
  • Journal article
    Allsopp LP, Collins ACZ, Hawkins E, Wood TE, Filloux Aet al., 2021,

    RpoN/Sfa2-dependent activation of the Pseudomonas aeruginosa H2-T6SS and its cognate arsenal of antibacterial toxins.

    , Nucleic Acids Res

    Pseudomonas aeruginosa uses three type six secretion systems (H1-, H2- and H3-T6SS) to manipulate its environment, subvert host cells and for microbial competition. These T6SS machines are loaded with a variety of effectors/toxins, many being associated with a specific VgrG. How P. aeruginosa transcriptionally coordinates the main T6SS clusters and the multiple vgrG islands spread through the genome is unknown. Here we show an unprecedented level of control with RsmA repressing most known T6SS-related genes. Moreover, each of the H2- and H3-T6SS clusters encodes a sigma factor activator (SFA) protein called, Sfa2 and Sfa3, respectively. SFA proteins are enhancer binding proteins necessary for the sigma factor RpoN. Using a combination of RNA-seq, ChIP-seq and molecular biology approaches, we demonstrate that RpoN coordinates the T6SSs of P. aeruginosa by activating the H2-T6SS but repressing the H1- and H3-T6SS. Furthermore, RpoN and Sfa2 control the expression of the H2-T6SS-linked VgrGs and their effector arsenal to enable very effective interbacterial killing. Sfa2 is specific as Sfa3 from the H3-T6SS cannot complement loss of Sfa2. Our study further delineates the regulatory mechanisms that modulate the deployment of an arsenal of T6SS effectors likely enabling P. aeruginosa to adapt to a range of environmental conditions.

  • Journal article
    Ortega D, Beeby M, 2021,

    How did the archaellum get its rotation?

    , Frontiers in Microbiology, ISSN: 1664-302X
  • Journal article
    Enbody ED, Sprehn CG, Abzhanov A, Bi H, Dobreva MP, Osborne OG, Rubin C-J, Grant PR, Grant BR, Andersson Let al., 2021,

    A multispecies BCO2 beak color polymorphism in the Darwin's finch radiation

    , CURRENT BIOLOGY, Vol: 31, Pages: 5597-+, ISSN: 0960-9822
  • Journal article
    Hamilton C, Olona A, Leishman S, MacDonald-Ramsahai K, Cockcroft S, Larrouy-Maumus G, Anand Pet al., 2021,

    NLRP3 inflammasome priming and activation are regulated by a novel phosphatidylinositol-dependent mechanism

    , BioRxiv
  • Journal article
    Woodward G, Morris O, Barquin J, Belgrano A, Bull C, de Eyto E, Friberg N, Guobergsson G, Layer-Dobra K, Lauridsen RB, Lewis HM, McGinnity P, Pawar S, Rosindell J, O'Gorman EJet al., 2021,

    Using Food Webs and Metabolic Theory to Monitor, Model, and Manage Atlantic Salmon-A Keystone Species Under Threat

    , FRONTIERS IN ECOLOGY AND EVOLUTION, Vol: 9, ISSN: 2296-701X
  • Journal article
    Fichtner F, Barbier FF, Kerr SC, Dudley C, Cubas P, Turnbull C, Brewer PB, Beveridge CAet al., 2021,

    Plasticity of bud outgrowth varies at cauline and rosette nodes in Arabidopsis thaliana.

    , Plant Physiol

    Shoot branching is a complex mechanism in which secondary shoots grow from buds that are initiated from meristems established in leaf axils. The model plant Arabidopsis (Arabidopsis thaliana) has a rosette leaf growth pattern in the vegetative stage. After flowering initiation, the main stem elongates with the top leaf primordia developing into cauline leaves. Meristems in Arabidopsis initiate in the axils of rosette or cauline leaves, giving rise to rosette or cauline buds, respectively. Plasticity in the process of shoot branching is regulated by resource and nutrient availability as well as by plant hormones. However, few studies have attempted to test whether cauline and rosette branching are subject to the same plasticity. Here, we addressed this question by phenotyping cauline and rosette branching in three Arabidopsis ecotypes and several Arabidopsis mutants with varied shoot architectures. Our results showed no negative correlation between cauline and rosette branch numbers in Arabidopsis, demonstrating that there is no trade-off between cauline and rosette bud outgrowth. Through investigation of the altered branching pattern of flowering pathway mutants and Arabidopsis ecotypes grown in various photoperiods and light regimes, we further elucidated that the number of cauline branches is closely related to flowering time. The number of rosette branches has an enormous plasticity compared with cauline branches and is influenced by genetic background, flowering time, light intensity and temperature. Our data reveal different levels of plasticity in the regulation of branching at rosette and cauline nodes and promote a framework for future branching analyses.

  • Journal article
    Jamshidiha M, Lanyon-Hogg T, Sutherell C, Craven G, Tersa M, De Vita E, Brustur D, Perez-Doraldo I, Hassan S, Petracca R, Morgan R, Sanz-Hernández M, Norman J, Armstrong A, Mann D, Cota E, Tate Eet al., 2021,

    Identification of the first structurally validated covalent ligands of the small GTPase RAB27A

    , RSC Medicinal Chemistry, ISSN: 2632-8682

    Rab27A is a small GTPase, which mediates transport and docking of secretory vesicles at the plasma membrane via protein–protein interactions (PPIs) with effector proteins. Rab27A promotes the growth and invasion of multiple cancer types such as breast, lung and pancreatic, by enhancing secretion of chemokines, metalloproteases and exosomes. The significant role of Rab27A in multiple cancer types and the minor role in adults suggest that Rab27A may be a suitable target to disrupt cancer metastasis. Similar to many GTPases, the flat topology of the Rab27A-effector PPI interface and the high affinity for GTP make it a challenging target for inhibition by small molecules. Reported co-crystal structures show that several effectors of Rab27A interact with the Rab27A SF4 pocket (‘WF-binding pocket’) via a conserved tryptophan–phenylalanine (WF) dipeptide motif. To obtain structural insight into the ligandability of this pocket, a novel construct was designed fusing Rab27A to part of an effector protein (fRab27A), allowing crystallisation of Rab27A in high throughput. The paradigm of KRas covalent inhibitor development highlights the challenge presented by GTPase proteins as targets. However, taking advantage of two cysteine residues, C123 and C188, that flank the WF pocket and are unique to Rab27A and Rab27B among the >60 Rab family proteins, we used the quantitative Irreversible Tethering (qIT) assay to identify the first covalent ligands for native Rab27A. The binding modes of two hits were elucidated by co-crystallisation with fRab27A, exemplifying a platform for identifying suitable lead fragments for future development of competitive inhibitors of the Rab27A-effector interaction interface, corroborating the use of covalent libraries to tackle challenging targets.

  • Journal article
    Tan BJ, Sugata K, Reda O, Matsuo M, Uchiyama K, Miyazato P, Hahaut V, Yamagishi M, Uchimaru K, Suzuki Y, Ueno T, Suzushima H, Katsuya H, Tokunaga M, Uchiyama Y, Nakamura H, Sueoka E, Utsunomiya A, Ono M, Satou Yet al., 2021,

    HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia/lymphoma.

    , J Clin Invest, Vol: 131

    Human T cell leukemia virus type 1 (HTLV-1) mainly infects CD4+ T cells and induces chronic, persistent infection in infected individuals, with some developing adult T cell leukemia/lymphoma (ATL). HTLV-1 alters cellular differentiation, activation, and survival; however, it is unknown whether and how these changes contribute to the malignant transformation of infected cells. In this study, we used single-cell RNA-sequencing and T cell receptor-sequencing to investigate the differentiation and HTLV-1-mediated transformation of T cells. We analyzed 87,742 PBMCs from 12 infected and 3 uninfected individuals. Using multiple independent bioinformatics methods, we demonstrated the seamless transition of naive T cells into activated T cells, whereby HTLV-1-infected cells in an activated state further transformed into ATL cells, which are characterized as clonally expanded, highly activated T cells. Notably, the greater the activation state of ATL cells, the more they acquire Treg signatures. Intriguingly, the expression of HLA class II genes in HTLV-1-infected cells was uniquely induced by the viral protein Tax and further upregulated in ATL cells. Functional assays revealed that HTLV-1-infected cells upregulated HLA class II molecules and acted as tolerogenic antigen-presenting cells to induce anergy of antigen-specific T cells. In conclusion, our study revealed the in vivo mechanisms of HTLV-1-mediated transformation and immune escape at the single-cell level.

  • Journal article
    Wong Y, Rosindell J, 2021,

    Dynamic visualisation of million-tip trees: the OneZoom project

    , Methods in Ecology and Evolution, ISSN: 2041-210X

    1. The complete tree of life is now available, but methods to visualise it are still needed to meet needs in research, teaching and science communication. Dynamic visualisation of million-tip trees requires many challenges in data synthesis, data handling and computer graphics to be overcome.2. Our approach is to automate data processing, synthesise data from a wide range of available sources, then to feed these data to a client-side visualisation engine in parts. We develop a way to store the whole tree topology locally in a highly compressed form, then dynamically populate metadata such as text and images as the user explores.3. The result is a seamless and smooth way to explore the complete tree of life, including images and metadata, even on relatively old mobile devices.4. The underlying methods developed have applications that transcend tree of life visualisation. For the whole complete tree, we describe automated ID mappings between well known resources without resorting to taxonomic name resolution, automated methods to collate sets of public domain representative images for higher taxa, and an index to measure public interest of individual species. 5. The visualisation layout and the client user interface are both abstracted components of the codebase enabling other zoomable tree layouts to be swapped in, and supporting multiple applications including exhibition kiosks and digital art.6. After 10 years of work, our tree of life explorer is now broadly complete, it has attracted nearly 1.5 million online users, and is backed by a novel long-term sustainability plan. We conclude our description of the OneZoom project by suggesting the next challenges that need to be solved in this field: extinct species and guided tours around the tree.

  • Journal article
    Wong Y, Rosindell J, 2021,

    Dynamic visualisation of million‐tip trees: The OneZoom project

    , Methods in Ecology and Evolution, ISSN: 2041-210X
  • Journal article
    Salvalaio M, Oliver N, Tiknaz D, Maximillian S, Kral N, Kim S-J, Sena Get al., 2021,

    Root electrotropism in Arabidopsis does not depend on auxin distribution but requires cytokinin biosynthesis

    , Plant Physiology, ISSN: 0032-0889

    Efficient foraging by plant roots relies on the ability to sense multiple physical and chemical cues in soil and to reorient growth accordingly (tropism). Root tropisms range from sensing gravity (gravitropism), light (phototropism), water (hydrotropism), touch (thigmotropism), and more. Electrotropism, also known as galvanotropism, is the phenomenon of aligning growth with external electric fields and currents. Although root electrotropism has been observed in a few species since the end of the 19th century, its molecular and physical mechanisms remain elusive, limiting its comparison with the more well-defined sensing pathways in plants. Here we provide a quantitative and molecular characterization of root electrotropism in the model system Arabidopsis (Arabidopsis thaliana), showing that it does not depend on an asymmetric distribution of the plant hormone auxin, but instead requires the biosynthesis of a second hormone, cytokinin. We also show that the dose-response kinetics of the early steps of root electrotropism follows a power law analogous to the one observed in some physiological reactions in animals. Future studies involving more extensive molecular and quantitative characterization of root electrotropism would represent a step towards a better understanding of signal integration in plants and would also serve as an independent outgroup for comparative analysis of electroreception in animals and fungi.

  • Journal article
    Kawahara R, Chernykh A, Alagesan K, Bern M, Cao W, Chalkley RJ, Cheng K, Choo MS, Edwards N, Goldman R, Hoffmann M, Hu Y, Huang Y, Kim JY, Kletter D, Liquet B, Liu M, Mechref Y, Meng B, Neelamegham S, Nguyen-Khuong T, Nilsson J, Pap A, Park GW, Parker BL, Pegg CL, Penninger JM, Phung TK, Pioch M, Rapp E, Sakalli E, Sanda M, Schulz BL, Scott NE, Sofronov G, Stadlmann J, Vakhrushev SY, Woo CM, Wu H-Y, Yang P, Ying W, Zhang H, Zhang Y, Zhao J, Zaia J, Haslam SM, Palmisano G, Yoo JS, Larson G, Khoo K-H, Medzihradszky KF, Kolarich D, Packer NH, Thaysen-Andersen Met al., 2021,

    Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis (vol 18, pg 1304, 2021)

    , NATURE METHODS, ISSN: 1548-7091

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