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  • 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
    Dechant B, Kattge J, Pavlick R, Schneider FD, Sabatini FM, Moreno-Martínez Á, Butler EE, van Bodegom PM, Vallicrosa H, Kattenborn T, Boonman CCF, Madani N, Wright IJ, Dong N, Feilhauer H, Peñuelas J, Sardans J, Aguirre-Gutiérrez J, Reich PB, Leitão PJ, Cavender-Bares J, Myers-Smith IH, Durán SM, Croft H, Prentice IC, Huth A, Rebel K, Zaehle S, Šímová I, Díaz S, Reichstein M, Schiller C, Bruelheide H, Mahecha M, Wirth C, Malhi Y, Townsend PAet al., 2024,

    Intercomparison of global foliar trait maps reveals fundamental differences and limitations of upscaling approaches

    , Remote Sensing of Environment, Vol: 311, ISSN: 0034-4257

    Foliar traits such as specific leaf area (SLA), leaf nitrogen (N), and phosphorus (P) concentrations play important roles in plant economic strategies and ecosystem functioning. Various global maps of these foliar traits have been generated using statistical upscaling approaches based on in-situ trait observations. Here, we intercompare such global upscaled foliar trait maps at 0.5° spatial resolution (six maps for SLA, five for N, three for P), categorize the upscaling approaches used to generate them, and evaluate the maps with trait estimates from a global database of vegetation plots (sPlotOpen). We disentangled the contributions from different plant functional types (PFTs) to the upscaled maps and quantified the impacts of using different plot-level trait metrics on the evaluation with sPlotOpen: community weighted mean (CWM) and top-of-canopy weighted mean (TWM). We found that the global foliar trait maps of SLA and N differ drastically and fall into two groups that are almost uncorrelated (for P only maps from one group were available). The primary factor explaining the differences between these groups is the use of PFT information combined with remote sensing-derived land cover products in one group while the other group mostly relied on environmental predictors alone. The maps that used PFT and corresponding land cover information exhibit considerable similarities in spatial patterns that are strongly driven by land cover. The maps not using PFTs show a lower level of similarity and tend to be strongly driven by individual environmental variables. Upscaled maps of both groups were moderately correlated to sPlotOpen data aggregated to the grid-cell level (R = 0.2–0.6) when processing sPlotOpen in a way that is consistent with the respective trait upscaling approaches, including the plot-level trait metric (CWM or TWM) and the scaling to the grid cells with or without accounting for fractional land cover. The impact of using TWM or CWM was relevant
  • Journal article
    Kabasakal BV, McFarlane CR, Cotton CAR, Schmidt A, Kung A, Lieber L, Murray JWet al., 2024,

    The crystal structure of Shethna protein II (FeSII) from Azotobacter vinelandii suggests a domain swap.

    , Acta Crystallogr D Struct Biol

    The Azotobacter vinelandii FeSII protein forms an oxygen-resistant complex with the nitrogenase MoFe and Fe proteins. FeSII is an adrenodoxin-type ferredoxin that forms a dimer in solution. Previously, the crystal structure was solved [Schlesier et al. (2016), J. Am. Chem. Soc. 138, 239-247] with five copies in the asymmetric unit. One copy is a normal adrenodoxin domain that forms a dimer with its crystallographic symmetry mate. The other four copies are in an `open' conformation with a loop flipped out exposing the 2Fe-2S cluster. The open and closed conformations were interpreted as oxidized and reduced, respectively, and the large conformational change in the open configuration allowed binding to nitrogenase. Here, the structure of FeSII was independently solved in the same crystal form. The positioning of the atoms in the unit cell is similar to the earlier report. However, the interpretation of the structure is different. The `open' conformation is interpreted as the product of a crystallization-induced domain swap. The 2Fe-2S cluster is not exposed to solvent, but in the crystal its interacting helix is replaced by the same helix residues from a crystal symmetry mate. The domain swap is complicated, as it is unusual in being in the middle of the protein rather than at a terminus, and it creates arrangements of molecules that can be interpreted in multiple ways. It is also cautioned that crystal structures should be interpreted in terms of the contents of the entire crystal rather than of one asymmetric unit.
  • Journal article
    Rosenkranz M, Nkumama IN, Ogwang R, Kraker S, Blickling M, Mwai K, Odera D, Tuju J, Fürle K, Frank R, Chepsat E, Kapulu MC, Osier FHAet al., 2024,

    Full-length MSP1 is a major target of protective immunity after controlled human malaria infection

    , Life Science Alliance, Vol: 7, ISSN: 2575-1077

    The merozoite surface protein 1 (MSP1) is the most abundant protein on the surface of the invasive merozoite stages of Plasmodium falciparum and has long been considered a key target of protective immunity. We used samples from a single controlled human malaria challenge study to test whether the full-length version of MSP1 (MSP1FL) induced antibodies that mediated Fc-IgG functional activity in five independent assays. We found that anti-MSP1FL antibodies induced complement fixation via C1q, monocyte-mediated phagocytosis, neutrophil respiratory burst, and natural killer cell degranulation as well as IFNγ production. Activity in each of these assays was strongly associated with protection. The breadth of MSP1-specific Fc-mediated effector functions was more strongly associated with protection than the individual measures and closely mirrored what we have previously reported using the same assays against merozoites. Our findings suggest that MSP1FL is an important target of functional antibodies that contribute to a protective immune response against malaria.
  • Journal article
    Sethi S, Bick IA, Chen M-Y, Crouzeilles R, Hillier BV, Lawson J, Lee C-Y, Liu S-H, Henrique de Freitas Parruco C, Rosten CM, Somveille M, Tuanmu M-N, Banks-Leite Cet al., 2024,

    Large-scale avian vocalisation detection delivers reliable global biodiversity insights

    , Proceedings of the National Academy of Sciences of USA, ISSN: 0027-8424
  • Journal article
    Ukleja M, Kricks L, Torrens G, Peschiera I, Rodrigues-Lopes I, Krupka M, García-Fernández J, Melero R, del Campo R, Eulalio A, Mateus A, López-Bravo M, Rico AI, Cava F, Lopez Det al., 2024,

    Flotillin-mediated stabilization of unfolded proteins in bacterial membrane microdomains

    , Nature Communications, Vol: 15

    <jats:title>Abstract</jats:title><jats:p>The function of many bacterial processes depends on the formation of functional membrane microdomains (FMMs), which resemble the lipid rafts of eukaryotic cells. However, the mechanism and the biological function of these membrane microdomains remain unclear. Here, we show that FMMs in the pathogen methicillin-resistant <jats:italic>Staphylococcus aureus</jats:italic> (MRSA) are dedicated to confining and stabilizing proteins unfolded due to cellular stress. The FMM scaffold protein flotillin forms a clamp-shaped oligomer that holds unfolded proteins, stabilizing them and favoring their correct folding. This process does not impose a direct energy cost on the cell and is crucial to survival of ATP-depleted bacteria, and thus to pathogenesis. Consequently, FMM disassembling causes the accumulation of unfolded proteins, which compromise MRSA viability during infection and cause penicillin re-sensitization due to PBP2a unfolding. Thus, our results indicate that FMMs mediate ATP-independent stabilization of unfolded proteins, which is essential for bacterial viability during infection.</jats:p>
  • Journal article
    Rebuffet L, Melsen JE, Escalière B, Basurto-Lozada D, Bhandoola A, Björkström NK, Bryceson YT, Castriconi R, Cichocki F, Colonna M, Davis DM, Diefenbach A, Ding Y, Haniffa M, Horowitz A, Lanier LL, Malmberg K-J, Miller JS, Moretta L, Narni-Mancinelli E, O'Neill LAJ, Romagnani C, Ryan DG, Sivori S, Sun D, Vagne C, Vivier Eet al., 2024,

    High-dimensional single-cell analysis of human natural killer cell heterogeneity.

    , Nat Immunol

    Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.
  • Journal article
    Saranholi BH, Franca FM, Vogler AP, Barlow J, de Mello FZV, Maldaner ME, Carvalho E, Gestich CC, Howes B, Banks-Leite C, Galetti PMet al., 2024,

    Testing and optimizing metabarcoding of iDNA from dung beetles to sample mammals in the hyperdiverse Neotropics

    , MOLECULAR ECOLOGY RESOURCES, Vol: 24, ISSN: 1755-098X
  • Journal article
    Howes B, Gonzalez-Suarez M, Banks-Leite C, Bellotto-Trigo FC, Betts MGet al., 2024,

    A global latitudinal gradient in the proportion of terrestrial vertebrate forest species

    , GLOBAL ECOLOGY AND BIOGEOGRAPHY, Vol: 33, ISSN: 1466-822X
  • Journal article
    Li Z, Di Vagno L, Chawla H, Ni Cheallaigh A, Critcher M, Sammon D, Briggs DC, Chung N, Chang V, Mahoney KE, Cioce A, Murphy LD, Chen Y-H, Narimatsu Y, Miller RL, Willems LI, Malaker SA, Huang ML, Miller GJ, Hohenester E, Schumann Bet al., 2024,

    Xylosyltransferase Bump-and-hole Engineering to Chemically Manipulate Proteoglycans in Mammalian Cells.

    , bioRxiv

    Mammalian cells orchestrate signalling through interaction events on their surfaces. Proteoglycans are an intricate part of these interactions, carrying large glycosaminoglycan polysaccharides that recruit signalling molecules. Despite their importance in development, cancer and neurobiology, a relatively small number of proteoglycans have been identified. In addition to the complexity of glycan extension, biosynthetic redundancy in the first protein glycosylation step by two xylosyltransferase isoenzymes XT1 and XT2 complicates annotation of proteoglycans. Here, we develop a chemical genetic strategy that manipulates the glycan attachment site of cellular proteoglycans. By employing a tactic termed bump- and-hole engineering, we engineer the two isoenzymes XT1 and XT2 to specifically transfer a chemically modified xylose analogue to target proteins. The chemical modification contains a bioorthogonal tag, allowing the ability to visualise and profile target proteins modified by both transferases in mammalian cells. The versatility of our approach allows pinpointing glycosylation sites by tandem mass spectrometry, and exploiting the chemical handle to manufacture proteoglycans with defined GAG chains for cellular applications. Engineered XT enzymes permit a view into proteoglycan biology that is orthogonal to conventional techniques in biochemistry.
  • Journal article
    Kourelis J, Schuster M, Demir F, Mattinson O, Krauter S, Kahlon PS, O'Grady R, Royston S, Bravo-Cazar AL, Mooney BC, Huesgen PF, Kamoun S, van der Hoorn RALet al., 2024,

    Bioengineering secreted proteases convert divergent Rcr3 orthologs and paralogs into extracellular immune co-receptors.

    , Plant Cell

    Secreted immune proteases Rcr3 (Required for Cladosporium resistance-3) and Pip1 (Phytophthora- inhibited protease-1) of tomato (Solanum lycopersicum) are both inhibited by Avr2 from the fungal plant pathogen Cladosporium fulvum. However, only Rcr3 acts as a decoy co-receptor that detects Avr2 in the presence of the Cf-2 immune receptor. Here, we identified crucial residues in tomato Rcr3 that are required for Cf-2-mediated signalling and bioengineered various proteases to trigger Avr2/Cf-2-dependent immunity. Despite substantial divergence in Rcr3 orthologs from eggplant (Solanum melongena) and tobacco (Nicotiana spp.), minimal alterations were sufficient to trigger Avr2/Cf-2-mediated immune signalling. By contrast, tomato Pip1 was bioengineered with 16 Rcr3-specific residues to initiate Avr2/Cf-2-triggered immune signalling. These residues cluster on one side of the protein next to the substrate-binding groove, indicating a potential Cf-2 interaction site. Our findings also revealed that Rcr3 and Pip1 have distinct substrate preferences determined by two variant residues, and that both are suboptimal for binding Avr2. This study advances our understanding of Avr2 perception and opens avenues to bioengineer proteases to broaden pathogen recognition in other crops.
  • Journal article
    Ba W, Nollet M, Yin C, Yu X, Wong S, Miao A, Beckwith E, Harding E, Ma Y, Yustos R, Vyssotski AL, Wisden W, Franks Net al., 2024,

    A REM-active basal ganglia circuit that regulates anxiety

    , Current Biology, ISSN: 0960-9822

    REM sleep has been hypothesized to promote emotional resilience, but any neuronal circuits mediating this have not been identified. We find that in mice, somatostatin (Som)neurons in the entopeduncular nucleus (EP Som )/internal globus pallidus are predominantly active during REM sleep. This unique REM activity is necessary and sufficient formaintaining normal REM sleep. Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively. Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula (LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic scheme to periodically inhibit the LHb over 4 days selectively removed a significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep, in part generated by the EP→LHb→VTA circuit identified here, could contribute to stabilizing reactions to habitual aversive stimuli.
  • Journal article
    Tica J, Chen H, LUO S, Chen M, Isalan Met al., 2024,

    Engineering tunable, low latency spatial computation with dual input quorum sensing promoters

    , ACS Synthetic Biology, Vol: 13, Pages: 1750-1761, ISSN: 2161-5063

    Quorum sensing signals have evolved for population-level signaling in bacterial communities and are versatile tools for engineering cell–cell signaling in synthetic biology projects. Here, we characterize the spatial diffusion of a palette of quorum sensing signals and find that their diffusion in agar can be predicted from their molecular weight with a simple power law. We also engineer novel dual- and multi-input promoters that respond to quorum-sensing diffusive signals for use in engineered genetic systems. We engineer a promoter scaffold that can be adapted for activation and repression by multiple diffusers simultaneously. Lastly, we combine the knowledge on diffusion dynamics with the novel genetic components to build a new generation of spatial, stripe-forming systems with a simplified design, improved robustness, tuneability, and response time.
  • Journal article
    Endres R, Matas-Gil A, 2024,

    Unraveling biochemical spatial patterns: machine learning approaches to the inverse problem of stationary Turing patterns

    , iScience, Vol: 27, ISSN: 2589-0042

    The diffusion-driven Turing instability is a potential mechanism for spatial pattern formation in numerous biological and chemical systems. However, engineering these patterns and demonstrating that they are produced by this mechanism is challenging. To address this, we aim to solve the inverse problem in artificial and experimental Turing patterns. This task is challenging since patterns are often corrupted by noise and slight changes in initial conditions can lead to different patterns. We used both least squares to explore the problem and physics-informed neural networks to build a noise-robust method. We elucidate the functionality of our network in scenarios mimicking biological noise levels and showcase its application using an experimentally obtained chemical pattern. The findings reveal the significant promise of machine learning in steering the creation of synthetic patterns in bioengineering, thereby advancing our grasp of morphological intricacies within biological systems while acknowledging existing limitations.
  • Journal article
    Collins ASP, Kurt H, Duggan C, Cotur Y, Coatsworth P, Naik A, Kaisti M, Bozkurt T, Güder Fet al., 2024,

    Parallel, continuous monitoring and quantification of programmed cell death in plant tissue

    , Advanced Science, Vol: 11, ISSN: 2198-3844

    Accurate quantification of hypersensitive response (HR) programmed cell death is imperative for understanding plant defense mechanisms and developing disease-resistant crop varieties. Here, a phenotyping platform for rapid, continuous-time, and quantitative assessment of HR is demonstrated: Parallel Automated Spectroscopy Tool for Electrolyte Leakage (PASTEL). Compared to traditional HR assays, PASTEL significantly improves temporal resolution and has high sensitivity, facilitating detection of microscopic levels of cell death. Validation is performed by transiently expressing the effector protein AVRblb2 in transgenic Nicotiana benthamiana (expressing the corresponding resistance protein Rpi-blb2) to reliably induce HR. Detection of cell death is achieved at microscopic intensities, where leaf tissue appears healthy to the naked eye one week after infiltration. PASTEL produces large amounts of frequency domain impedance data captured continuously. This data is used to develop supervised machine-learning (ML) models for classification of HR. Input data (inclusive of the entire tested concentration range) is classified as HR-positive or negative with 84.1% mean accuracy (F1 score = 0.75) at 1 h and with 87.8% mean accuracy (F1 score = 0.81) at 22 h. With PASTEL and the ML models produced in this work, it is possible to phenotype disease resistance in plants in hours instead of days to weeks.
  • Journal article
    Manser CL, Perez-Carrasco R, 2024,

    A mathematical framework for measuring and tuning tempo in developmental gene regulatory networks.

    , Development, Vol: 151

    Embryo development is a dynamic process governed by the regulation of timing and sequences of gene expression, which control the proper growth of the organism. Although many genetic programmes coordinating these sequences are common across species, the timescales of gene expression can vary significantly among different organisms. Currently, substantial experimental efforts are focused on identifying molecular mechanisms that control these temporal aspects. In contrast, the capacity of established mathematical models to incorporate tempo control while maintaining the same dynamical landscape remains less understood. Here, we address this gap by developing a mathematical framework that links the functionality of developmental programmes to the corresponding gene expression orbits (or landscapes). This unlocks the ability to find tempo differences as perturbations in the dynamical system that preserve its orbits. We demonstrate that this framework allows for the prediction of molecular mechanisms governing tempo, through both numerical and analytical methods. Our exploration includes two case studies: a generic network featuring coupled production and degradation, with a particular application to neural progenitor differentiation; and the repressilator. In the latter, we illustrate how altering the dimerisation rates of transcription factors can decouple the tempo from the shape of the resulting orbits. We conclude by highlighting how the identification of orthogonal molecular mechanisms for tempo control can inform the design of circuits with specific orbits and tempos.
  • Journal article
    Miao A, Luo T, Hsieh B, Edge CJ, Gridley M, Wong RTC, Constandinou TG, Wisden W, Franks NPet al., 2024,

    Brain clearance is reduced during sleep and anesthesia (vol 27, pg 1046, 2024)

    , NATURE NEUROSCIENCE, ISSN: 1097-6256
  • Journal article
    Joyce M, Falconio FA, Blackhurst L, Prieto-Godino L, French AS, Gilestro GFet al., 2024,

    Divergent evolution of sleep in Drosophila species

    , Nature Communications, Vol: 15, ISSN: 2041-1723

    Living organisms synchronize their biological activities with the earth’s rotation through the circadian clock, a molecular mechanism that regulates biology and behavior daily. This synchronization factually maximizes positive activities (e.g., social interactions, feeding) during safe periods, and minimizes exposure to dangers (e.g., predation, darkness) typically at night. Beyond basic circadian regulation, some behaviors like sleep have an additional layer of homeostatic control, ensuring those essential activities are fulfilled. While sleep is predominantly governed by the circadian clock, a secondary homeostatic regulator, though not well-understood, ensures adherence to necessary sleep amounts and hints at a fundamental biological function of sleep beyond simple energy conservation and safety. Here we explore sleep regulation across seven Drosophila species with diverse ecological niches, revealing that while circadian-driven sleep aspects are consistent, homeostatic regulation varies significantly. The findings suggest that in Drosophilids, sleep evolved primarily for circadian purposes. The more complex, homeostatically regulated functions of sleep appear to have evolved independently in a species-specific manner, and are not universally conserved. This laboratory model may reproduce and recapitulate primordial sleep evolution.
  • Journal article
    Nkumama IN, Ogwang R, Odera D, Musasia F, Mwai K, Nyamako L, Murungi L, Tuju J, Fürle K, Rosenkranz M, Kimathi R, Njuguna P, Hamaluba M, Kapulu MC, Frank R, CHMI-SIKA study team, Osier FHAet al., 2024,

    Breadth of Fc-mediated effector function correlates with clinical immunity following human malaria challenge.

    , Immunity, Vol: 57, Pages: 1215-1224.e6

    Malaria is a life-threatening disease of global health importance, particularly in sub-Saharan Africa. The growth inhibition assay (GIA) is routinely used to evaluate, prioritize, and quantify the efficacy of malaria blood-stage vaccine candidates but does not reliably predict either naturally acquired or vaccine-induced protection. Controlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection. We leveraged this platform to undertake a head-to-head comparison of seven functional antibody assays that are relevant to immunity against the erythrocytic merozoite stage of Plasmodium falciparum. Fc-mediated effector functions were strongly associated with protection from clinical symptoms of malaria and exponential parasite multiplication, while the gold standard GIA was not. The breadth of Fc-mediated effector function discriminated clinical immunity following the challenge. These findings present a shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.
  • Journal article
    Haber DA, Arien Y, Lamdan LB, Alcalay Y, Zecharia C, Krsticevic F, Yonah ES, Avraham RD, Krzywinska E, Krzywinski J, Marois E, Windbichler N, Papathanos PAet al., 2024,

    Targeting mosquito X-chromosomes reveals complex transmission dynamics of sex ratio distorting gene drives.

    , Nat Commun, Vol: 15

    Engineered sex ratio distorters (SRDs) have been proposed as a powerful component of genetic control strategies designed to suppress harmful insect pests. Two types of CRISPR-based SRD mechanisms have been proposed: X-shredding, which eliminates X-bearing sperm, and X-poisoning, which eliminates females inheriting disrupted X-chromosomes. These differences can have a profound impact on the population dynamics of SRDs when linked to the Y-chromosome: an X-shredder is invasive, constituting a classical meiotic Y-drive, whereas X-poisoning is self-limiting, unable to invade but also insulated from selection. Here, we establish X-poisoning strains in the malaria vector Anopheles gambiae targeting three X-linked genes during spermatogenesis, resulting in male bias. We find that sex distortion is primarily driven by a loss of X-bearing sperm, with limited evidence for postzygotic lethality of female progeny. By leveraging a Drosophila melanogaster model, we show unambiguously that engineered SRD traits can operate differently in these two insects. Unlike X-shredding, X-poisoning could theoretically operate at early stages of spermatogenesis. We therefore explore premeiotic Cas9 expression to target the mosquito X-chromosome. We find that, by pre-empting the onset of meiotic sex chromosome inactivation, this approach may enable the development of Y-linked SRDs if mutagenesis of spermatogenesis-essential genes is functionally balanced.
  • Journal article
    Smith T, Mishra S, Dorigatti I, Dixit M, Tristem M, Pearse Wet al., 2024,

    Differential responses of SARS-CoV-2 variants to environmental drivers during their selective sweeps

    , Scientific Reports, Vol: 14, ISSN: 2045-2322

    Previous work has shown that environmental variables affect SARS-CoV-2 transmission, but it is unclear whether different strains show similar environmental responses. Here we leverage genetic data on the transmission of three (Alpha, Delta and Omicron BA.1) variants of SARS-CoV-2 throughout England, to unpick the roles that climate and public-health interventions play in the circulation of this virus. We find evidence for enhanced transmission of the virus in colder conditions in the first variant selective sweep (of Alpha, in winter), but limited evidence of an impact of climate in either the second (of Delta, in the summer, when vaccines were prevalent) or third sweep (of Omicron, in the winter, during a successful booster-vaccination campaign). We argue that the results for Alpha are to be expected if the impact of climate is non-linear: we find evidence of an asymptotic impact of temperature on the alpha variant transmission rate. That is, at lower temperatures, the influence of temperature on transmission is much higher than at warmer temperatures. As with the initial spread of SARS-CoV-2, however, the overwhelming majority of variation in disease transmission is explained by the intrinsic biology of the virus and public-health mitigation measures. Specifically, when vaccination rates are high, a major driver of the spread of a new variant is it’s ability to evade immunity, and any climate effects are secondary (as evidenced for Delta and Omicron). Climate alone cannot describe the transmission dynamics of emerging SARS-CoV-2 variants.
  • Journal article
    Baxter JM, Hutchison CDM, Fadini A, Maghlaoui K, Cordon-Preciado V, Morgan RML, Agthe M, Horrell S, Tellkamp F, Mehrabi P, Pfeifer Y, Muller-Werkmeister HM, von Stetten D, Pearson AR, van Thor JJet al., 2024,

    Power Density Titration of Reversible Photoisomerization of a Fluorescent Protein Chromophore in the Presence of Thermally Driven Barrier Crossing Shown by Quantitative Millisecond Serial Synchrotron X-ray Crystallography

    , JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 146, Pages: 16394-16403, ISSN: 0002-7863
  • Journal article
    Cawood EE, Baker E, Edwards TA, Woolfson DN, Karamanos TK, Wilson AJet al., 2024,

    Understanding β-strand mediated protein-protein interactions: tuning binding behaviour of intrinsically disordered sequences by backbone modification

    , CHEMICAL SCIENCE, ISSN: 2041-6520
  • Journal article
    Fu Z, Ciais P, Wigneron J-P, Gentine P, Feldman AF, Makowski D, Viovy N, Kemanian AR, Goll DS, Stoy PC, Prentice IC, Yakir D, Liu L, Ma H, Li X, Huang Y, Yu K, Zhu P, Li X, Zhu Z, Lian J, Smith WKet al., 2024,

    Global critical soil moisture thresholds of plant water stress.

    , Nat Commun, Vol: 15

    During extensive periods without rain, known as dry-downs, decreasing soil moisture (SM) induces plant water stress at the point when it limits evapotranspiration, defining a critical SM threshold (θcrit). Better quantification of θcrit is needed for improving future projections of climate and water resources, food production, and ecosystem vulnerability. Here, we combine systematic satellite observations of the diurnal amplitude of land surface temperature (dLST) and SM during dry-downs, corroborated by in-situ data from flux towers, to generate the observation-based global map of θcrit. We find an average global θcrit of 0.19 m3/m3, varying from 0.12 m3/m3 in arid ecosystems to 0.26 m3/m3 in humid ecosystems. θcrit simulated by Earth System Models is overestimated in dry areas and underestimated in wet areas. The global observed pattern of θcrit reflects plant adaptation to soil available water and atmospheric demand. Using explainable machine learning, we show that aridity index, leaf area and soil texture are the most influential drivers. Moreover, we show that the annual fraction of days with water stress, when SM stays below θcrit, has increased in the past four decades. Our results have important implications for understanding the inception of water stress in models and identifying SM tipping points.
  • Journal article
    Lane BJ, Ma Y, Yan N, Wang B, Ackermann K, Karamanos TK, Bode BE, Pliotas Cet al., 2024,

    Monitoring the conformational ensemble and lipid environment of a mechanosensitive channel under cyclodextrin-induced membrane tension.

    , Structure, Vol: 32, Pages: 739-750.e4

    Membrane forces shift the equilibria of mechanosensitive channels enabling them to convert mechanical cues into electrical signals. Molecular tools to stabilize and methods to capture their highly dynamic states are lacking. Cyclodextrins can mimic tension through the sequestering of lipids from membranes. Here we probe the conformational ensemble of MscS by EPR spectroscopy, the lipid environment with NMR, and function with electrophysiology under cyclodextrin-induced tension. We show the extent of MscS activation depends on the cyclodextrin-to-lipid ratio, and that lipids are depleted slower when MscS is present. This has implications in MscS' activation kinetics when distinct membrane scaffolds such as nanodiscs or liposomes are used. We find MscS transits from closed to sub-conducting state(s) before it desensitizes, due to the lack of lipid availability in its vicinity required for closure. Our approach allows for monitoring tension-sensitive states in membrane proteins and screening molecules capable of inducing molecular tension in bilayers.
  • Journal article
    Lu Y, Duman R, Beilsten-Edmands J, Winter G, Basham M, Evans G, Kamps JJAG, Orville AM, Kwong H-S, Beis K, Armour W, Wagner Aet al., 2024,

    Ray-tracing analytical absorption correction for X-ray crystallography based on tomographic reconstructions.

    , J Appl Crystallogr, Vol: 57, Pages: 649-658, ISSN: 0021-8898

    Processing of single-crystal X-ray diffraction data from area detectors can be separated into two steps. First, raw intensities are obtained by integration of the diffraction images, and then data correction and reduction are performed to determine structure-factor amplitudes and their uncertainties. The second step considers the diffraction geometry, sample illumination, decay, absorption and other effects. While absorption is only a minor effect in standard macromolecular crystallography (MX), it can become the largest source of uncertainty for experiments performed at long wavelengths. Current software packages for MX typically employ empirical models to correct for the effects of absorption, with the corrections determined through the procedure of minimizing the differences in intensities between symmetry-equivalent reflections; these models are well suited to capturing smoothly varying experimental effects. However, for very long wavelengths, empirical methods become an unreliable approach to model strong absorption effects with high fidelity. This problem is particularly acute when data multiplicity is low. This paper presents an analytical absorption correction strategy (implemented in new software AnACor) based on a volumetric model of the sample derived from X-ray tomography. Individual path lengths through the different sample materials for all reflections are determined by a ray-tracing method. Several approaches for absorption corrections (spherical harmonics correction, analytical absorption correction and a combination of the two) are compared for two samples, the membrane protein OmpK36 GD, measured at a wavelength of λ = 3.54 Å, and chlorite dismutase, measured at λ = 4.13 Å. Data set statistics, the peak heights in the anomalous difference Fourier maps and the success of experimental phasing are used to compare the results from the different absorption correction approaches. The strategies using the new analytical absorptio
  • Journal article
    Woubshete M, Cioccolo S, Byrne B, 2024,

    Advances in membrane mimetic systems for manipulation and analysis of membrane proteins; detergents, polymers, lipids and scaffolds

    , ChemPlusChem, Vol: 89, ISSN: 2192-6506

    Extracting membrane proteins from the hydrophobic environment of the biological membrane, in a physiologically relevant and stable state, suitable for downstream analysis remains a challenge. The traditional route to membrane protein extraction has been to use detergents and the last 15 years or so have seen a veritable explosion in the development of novel detergents with improved properties, making them more suitable for individual proteins and specific applications. There have also been significant advances in the development of encapsulation of membrane proteins in lipid based nanodiscs, either directly from the native membrane using polymers allowing effective capture of the protein and protein-associated membrane lipids, or via reconstitution of detergent extracted and purified protein into nanodiscs of defined lipid composition. All of these advances have been successfully applied to the study of membrane proteins via a range of techniques and there have been some spectacular membrane protein structures solved. In addition, the first detailed structural and biophysical analyses of membrane proteins retained within a biological membrane have been reported. Here we summarise and review the recent advances with respect to these new agents and systems for membrane protein extraction, reconstitution and analysis.
  • Journal article
    Oqua AI, Manchanda Y, McGlone ER, Jones B, Rouse S, Tomas Aet al., 2024,

    Lipid regulation of the glucagon receptor family

    , Journal of Endocrinology, Vol: 261, ISSN: 0022-0795

    The glucagon receptor family are typical class B1 G protein-coupled receptors (GPCRs) with important roles in metabolism, including the control of pancreas, brain, and liver function. As proteins with seven transmembrane domains, GPCRs are intimately in contact with lipid bilayers and therefore can be putatively regulated by interactions with their lipidic components, including cholesterol, sphingolipids, and other lipid species. Additionally, these receptors, as well as the agonists they bind to, can undergo lipid modifications, which can influence their binding capacity and/or elicit modified or biased signalling profiles. While the effect of lipids, and in particular cholesterol, has been widely studied for other GPCR classes, information about their role in regulating the glucagon receptor family is only beginning to emerge. Here we summarise our current knowledge on the effects of cholesterol modulation of glucagon receptor family signalling and trafficking profiles, as well as existing evidence for specific lipid-receptor binding and indirect effects of lipids via lipid modification of cognate agonists. Finally, we discuss the different methodologies that can be employed to study lipid-receptor interactions and summarise the importance of this area of investigation to increase our understanding of the biology of this family of metabolically relevant receptors.
  • Journal article
    Delhaye G, van der Linde S, Bauman D, Orme CDL, Suz LM, Bidartondo MIet al., 2024,

    Ectomycorrhizal fungi are influenced by ecoregion boundaries across Europe

    , Global Ecology and Biogeography, Vol: 33, ISSN: 1466-822X

    AimEcoregions and the distance decay in community similarity are fundamental concepts in biogeography and conservation biology that are well supported across plants and animals, but not fungi. Here we test the relevance of these concepts for ectomycorrhizal (ECM) fungi in temperate and boreal regions.LocationEurope.Time Period2008–2015.Major Taxa StudiedEctomycorrhizal fungi.MethodsWe used a large dataset of ~24,000 ectomycorrhizas, assigned to 1350 operational taxonomic units, collected from 129 forest plots via a standardized protocol. We investigated the relevance of ecoregion delimitations for ECM fungi through complementary methodological approaches based on distance decay models, multivariate analyses and indicator species analyses. We then evaluated the effects of host tree and climate on the observed biogeographical distributions.ResultsEcoregions predict large-scale ECM fungal biodiversity patterns. This is partly explained by climate differences between ecoregions but independent from host tree distribution. Basidiomycetes in the orders Russulales and Atheliales and producing epigeous fruiting bodies, with potentially short-distance dispersal, show the best agreement with ecoregion boundaries. Host tree distribution and fungal abundance (as opposed to presence/absence only) are important to uncover biogeographical patterns in mycorrhizas.Main ConclusionsEcoregions are useful units to investigate eco-evolutionary processes in mycorrhizal fungal communities and for conservation decision-making that includes fungi.
  • Journal article
    Cai JA, Christophides GK, 2024,

    Immune interactions between mosquitoes and microbes during midgut colonization

    , CURRENT OPINION IN INSECT SCIENCE, Vol: 63, ISSN: 2214-5745

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