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  • Journal article
    Kabasakal BV, Cotton CAR, Murray JW, 2024,

    Dynamic lid domain of Chloroflexus aurantiacus Malonyl-CoA reductase controls the reaction.

    , Biochimie, Vol: 219, Pages: 12-20, ISSN: 0300-9084

    Malonyl-Coenzyme A Reductase (MCR) in Chloroflexus aurantiacus, a characteristic enzyme of the 3-hydroxypropionate (3-HP) cycle, catalyses the reduction of malonyl-CoA to 3-HP. MCR is a bi-functional enzyme; in the first step, malonyl-CoA is reduced to the free intermediate malonate semialdehyde by the C-terminal region of MCR, and this is further reduced to 3-HP by the N-terminal region of MCR. Here we present the crystal structures of both N-terminal and C-terminal regions of the MCR from C. aurantiacus. A catalytic mechanism is suggested by ligand and substrate bound structures, and structural and kinetic studies of MCR variants. Both MCR structures reveal one catalytic, and one non-catalytic SDR (short chain dehydrogenase/reductase) domain. C-terminal MCR has a lid domain which undergoes a conformational change and controls the reaction. In the proposed mechanism of the C-terminal MCR, the conversion of malonyl-CoA to malonate semialdehyde is based on the reduction of malonyl-CoA by NADPH, followed by the decomposition of the hemithioacetal to produce malonate semialdehyde and coenzyme A. Conserved arginines, Arg734 and Arg773 are proposed to play key roles in the mechanism and conserved Ser719, and Tyr737 are other essential residues forming an oxyanion hole for the substrate intermediates.

  • Journal article
    Majumdar A, Upadhyay MK, Giri B, Yadav P, Moulick D, Sarkar S, Thakur BK, Sahu K, Srivastava AK, Buck M, Tibbett M, Jaiswal MK, Roychowdhury Tet al., 2024,

    Sustainable water management in rice cultivation reduces arsenic contamination, increases productivity, microbial molecular response, and profitability.

    , J Hazard Mater, Vol: 466

    Arsenic (As) and silicon (Si) are two structurally competitive natural elements where Si minimises As accumulation in rice plants, and based on this two-year field trial, the study proposes adopting alternating wetting and drying (AWD) irrigation as a sustainable water management strategy allowing greater Si availability. This field-based project is the first report on AWD's impact on As-Si distribution in fluvio-alluvial soils of the entire Ganga valley (24 study sites, six divisions), seasonal variance (pre-monsoon and monsoon), rice plant anatomy and productivity, soil microbial diversity, microbial gene ontology profiling and associated metabolic pathways. Under AWD to flooded and pre-monsoon to monsoon cultivations, respectively, greater Si availability was achieved and As-bioavailability was reduced by 8.7 ± 0.01-9.2 ± 0.02% and 25.7 ± 0.09-26.1 ± 0.01%. In the pre-monsoon and monsoon seasons, the physiological betterment of rice plants led to the high rice grain yield under AWD improved by 8.4 ± 0.07% and 10.0 ± 0.07%, proving the economic profitability. Compared to waterlogging, AWD evidences as an optimal soil condition for supporting soil microbial communities in rice fields, allowing diverse metabolic activities, including As-resistance, and active expression of As-responsive genes and gene products. Greater expressions of gene ontological terms and complex biochemical networking related to As metabolism under AWD proved better cellular, genetic and environmental responsiveness in microbial communities. Finally, by implementing AWD, groundwater usage can be reduced, lowering the cost of pumping and field management and generating an economic profit for farmers. These combined assessments prove the acceptability of AWD for the establishment of multiple sustainable development goals (SDGs).

  • Thesis dissertation
    Morrison A, 2024,

    Development of Improved Cultivation Methods for Environmental Microorganisms

    Cultivation of bacteria remains an essential prerequisite for numerous research and biotechnological applications. Despite their ubiquity, only a minority of environmental bacteria are cultivable using standard techniques. Therefore, a vast microbial ‘dark matter’ awaits exploration for valuable therapeutics or research potential. Despite innovations in enhanced cultivation techniques, limitations remain including throughput, dependencies on environmental factors or abrupt transitions of microorganisms from native to laboratory conditions. This thesis addresses these challenges with the development, optimisation, and experimental assessment of two novel cultivation methodologies. The first methodology allows for the gradual transition and acclimatisation of microorganisms from native environments to culture media using the novel Enhanced Domestication (EDEN) device. Compared to the instantaneous transition, acclimatisation of pond water bacteria to R2A culture media significantly enhanced cultivation diversity, colony yield and greater taxonomic range of isolates including those previously reported to be recalcitrant to cultivation. Moreover, likely novel taxa cultivated with EDEN exhibited antimicrobial activity against methicillin-resistant Staphylococcus aureus. The second methodology involves the development of a cell encapsulation apparatus, termed Bacterial Encapsulation and Containment (BEAD), enabling microinjection and cultivation of bacteria within alginate hydrogel beads using an automated pneumatic pump system. The performance of in situ cultivation with BEAD-encapsulated bacteria were assessed using the newly developed cultivation cassettes growth chambers. The findings propose enhanced cultivation strategies to unlock the biosynthetic potential of uncultured environmental bacteria.

  • Journal article
    Osier FHA, 2024,

    Antibody-Dependent Respiratory Burst against Plasmodium falciparum Merozoites in Individuals Living in an Area with Declining Malaria Transmission

    , Vaccines, ISSN: 2076-393X
  • Journal article
    Neyret M, Le Provost G, Boesing AL, Schneider FD, Baulechner D, Bergmann J, de Vries FT, Fiore-Donno AM, Geisen S, Goldmann K, Merges A, Saifutdinov RA, Simons NK, Tobias JA, Zaitsev AS, Gossner MM, Jung K, Kandeler E, Krauss J, Penone C, Schloter M, Schulz S, Staab M, Wolters V, Apostolakis A, Birkhofer K, Boch S, Boeddinghaus RS, Bolliger R, Bonkowski M, Buscot F, Dumack K, Fischer M, Gan HY, Heinze J, Hölzel N, John K, Klaus VH, Kleinebecker T, Marhan S, Müller J, Renner SC, Rillig MC, Schenk NV, Schöning I, Schrumpf M, Seibold S, Socher SA, Solly EF, Teuscher M, van Kleunen M, Wubet T, Manning Pet al., 2024,

    A slow-fast trait continuum at the whole community level in relation to land-use intensification.

    , Nat Commun, Vol: 15

    Organismal functional strategies form a continuum from slow- to fast-growing organisms, in response to common drivers such as resource availability and disturbance. However, whether there is synchronisation of these strategies at the entire community level is unclear. Here, we combine trait data for >2800 above- and belowground taxa from 14 trophic guilds spanning a disturbance and resource availability gradient in German grasslands. The results indicate that most guilds consistently respond to these drivers through both direct and trophically mediated effects, resulting in a 'slow-fast' axis at the level of the entire community. Using 15 indicators of carbon and nutrient fluxes, biomass production and decomposition, we also show that fast trait communities are associated with faster rates of ecosystem functioning. These findings demonstrate that 'slow' and 'fast' strategies can be manifested at the level of whole communities, opening new avenues of ecosystem-level functional classification.

  • Journal article
    Olechnowicz A, Blatkiewicz M, Jopek K, Isalan M, Mielcarek M, Rucinski Met al., 2024,

    Deregulated Transcriptome as a Platform for Adrenal Huntington’s Disease-Related Pathology

    , International Journal of Molecular Sciences, ISSN: 1422-0067
  • Report
    Benton J, Jimenez Zarco J, Banks A, Kakadellis S, Lee KY, Lee PH, Romain C, Wright S, von Holstein Iet al., 2024,

    Using microbes to remove microplastics from wastewater and sewage sludge

    , London, Publisher: Institute for Molecular Science and Engineering, Briefing paper No. 11

    Microplastics are a widespread form of plastic pollution. There is increasing evidence that they are a threat to human health and the environment. Microplastics in domestic and industrial wastewater become concentrated in sewage sludge during wastewater treatment processes. In 2020, water companies in England produced more than 800,000 tonnes of sewage sludge from urban wastewater. More than 90% of UK sewage sludge is spread on agricultural land as a fertilizer and soil conditioner. This provides a pathway for microplastics to enter the terrestrial environment. There is currently no UK legislation defining safe limits for microplastics in sludge and soils but future regulation is a possibility. There is currently no technology available to remove microplastics from wastewater treatment processes or the resulting sludge. Safe limits for microplastics in treated sewage sludge, soils and water bodies should be identified. This will require a survey of the extent of microplastic pollution throughout the UK, including concentration, identity and characteristics of microplastics in each environmental reservoir, and understanding how microplastics affect different living organisms. Microbes or fungi that break down plastic could be added to existing wastewater treatment process to remove microplastics and prevent their release into the environment. Alternatively, only the active enzymes (rather than the live microorganisms) could be added to the process. Currently, only polyester microplastics (11% of the total microplastic burden) could be treated in this way. Different microorganisms would have to be discovered or developed to tackle other common microplastic polymers such as polypropylene or polyethylene.

  • Journal article
    Makrydaki E, Donini R, Krueger A, Royle K, Moya Ramirez I, Kuntz DA, Rose DR, Haslam SM, Polizzi KM, Kontoravdi Cet al., 2024,

    Immobilized enzyme cascade for targeted glycosylation

    , Nature Chemical Biology, ISSN: 1552-4450

    Glycosylation is a critical post-translational protein modification that affects folding, half-life and functionality. Glycosylation is a non-templated and heterogeneous process because of the promiscuity of the enzymes involved. We describe a platform for sequential glycosylation reactions for tailored sugar structures (SUGAR-TARGET) that allows bespoke, controlled N-linked glycosylation in vitro enabled by immobilized enzymes produced with a one-step immobilization/purification method. We reconstruct a reaction cascade mimicking a glycosylation pathway where promiscuity naturally exists to humanize a range of proteins derived from different cellular systems, yielding near-homogeneous glycoforms. Immobilized β-1,4-galactosyltransferase is used to enhance the galactosylation profile of three IgGs, yielding 80.2-96.3% terminal galactosylation. Enzyme recycling is demonstrated for a reaction time greater than 80 h. The platform is easy to implement, modular and reusable and can therefore produce homogeneous glycan structures derived from various hosts for functional and clinical evaluation.

  • Journal article
    Drury JP, Clavel J, Tobias JA, Rolland J, Sheard C, Morlon Het al., 2024,

    Limited ecological opportunity influences the tempo of morphological evolution in birds

    , Current Biology, Vol: 34, Pages: 661-669.E4, ISSN: 0960-9822

    According to classic models of lineage diversification and adaptive radiation, phenotypic evolution should accelerate in the context of ecological opportunity and slow down when niches become saturated.1,2 However, only weak support for these ideas has been found in nature, perhaps because most analyses make the biologically unrealistic assumption that clade members contribute equally to reducing ecological opportunity, even when they occur in different continents or specialize on different habitats and diets. To view this problem through a different lens, we adapted a new phylogenetic modeling approach that accounts for the fact that competition for ecological opportunity only occurs between species that coexist and share similar habitats and diets. Applying this method to trait data for nearly all extant species of landbirds,3 we find a widespread signature of decelerating trait evolution in lineages adapted to similar habitats or diets. The strength of this pattern was consistent across latitudes when comparing tropical and temperate assemblages. Our results provide little support for the idea that increased diversity and tighter packing of niches accentuates evolutionary slowdowns in the tropics and instead suggest that limited ecological opportunity can be an important factor determining the rate of morphological diversification at a global scale.

  • 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

    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 using these new approaches. 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
    Guder F, Coatsworth P, Bozkurt O, Cotur Y, Collins AS-P, Olenik S, Zhou Z, Naik A, Asfour T, Gonzalez-Macia L, Chao D-Yet al., 2024,

    Time-resolved chemical monitoring of whole plant roots with printed electrochemical sensors and machine learning

    , Science Advances, Vol: 10, ISSN: 2375-2548

    Traditional single-point measurements fail to capture dynamic chemical responses of plants, which are complex, nonequilibrium biological systems. We report TETRIS (time-resolved electrochemical technology for plant root environment in situ chemical sensing), a real-time chemical phenotyping system for continuously monitoring chemical signals in the often-neglected plant root environment. TETRIS consisted of low-cost, highly scalable screen-printed electrochemical sensors for monitoring concentrations of salt, pH, and H2O2 in the root environment of whole plants, where multiplexing allowed for parallel sensing operation. TETRIS was used to measure ion uptake in tomato, kale, and rice and detected differences between nutrient and heavy metal ion uptake. Modulation of ion uptake with ion channel blocker LaCl3 was monitored by TETRIS and machine learning used to predict ion uptake. TETRIS has the potential to overcome the urgent “bottleneck” in high-throughput screening in producing high-yielding plant varieties with improved resistance against stress.

  • Journal article
    D'Amato R, Taxiarchi C, Galardini M, Trusso A, Minuz RL, Grilli S, Somerville AGT, Shittu D, Khalil AS, Galizi R, Crisanti A, Simoni A, Müller Ret al., 2024,

    Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages.

    , Nat Commun, Vol: 15

    CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. A doublesex-targeting gene drive was able to suppress laboratory Anopheles mosquito populations in small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework suggest that systems able to modulate or revert the action of gene drives, could be part of post-release risk-mitigation plans. In this study, we challenge an AcrIIA4-based anti-drive to inhibit gene drive spread in age-structured Anopheles gambiae population under complex feeding and behavioural conditions. A stochastic model predicts the experimentally-observed genotype dynamics in age-structured populations in medium-sized cages and highlights the necessity of large-sized cage trials. These experiments and experimental-modelling framework demonstrate the effectiveness of the anti-drive in different scenarios, providing further corroboration for its use in controlling the spread of gene drive in Anopheles.

  • Journal article
    Hatfield JH, Banks-Leite C, Barlow J, Lees AC, Tobias JAet al., 2024,

    Constraints on avian seed dispersal reduce potential for resilience in degraded tropical forests

    , Functional Ecology, Vol: 38, Pages: 315-326, ISSN: 0269-8463

    Seed dispersal is fundamental to tropical forest resilience. Forest loss or degradation typically leads to defaunation, altering seed transfer dynamics and impairing the ability of forested habitats to regenerate or recover from perturbation. However, the extent of defaunation, and its likely impacts on the seed dispersers needed to restore highly degraded or clear-felled areas, remains poorly understood in tropical forest landscapes. To quantify defaunation of seed-dispersing birds, we used field survey data from 499 transects in three forested regions of Brazil, first comparing the observed assemblages with those predicted by geographic range maps, and then assessing habitat associations of frugivores across land cover gradients. We found that current bird assemblages have lower functional diversity (FD) than predicted by species range maps in Amazonia (4%–6%), with a greater reduction in FD (28%) for the Atlantic Forest, which has been more heavily deforested for a longer period. Direct measures of seed dispersal are difficult to obtain, so we focused on potential seed transfer inferred from shared species occurrence. Of 83 predominantly frugivorous bird species recorded in relatively intact forests, we show that 10% were absent from degraded forest, and 57% absent from the surrounding matrix of agricultural land covers, including many large-gaped species. Of 112 frugivorous species using degraded forest, 47% were absent from matrix habitats. Overall, frugivores occurring in both intact forest and matrix habitats were outnumbered by (mostly small-gaped) frugivores occurring in both degraded forest and matrix habitats (23 additional species; 64% higher diversity). These findings suggest that birds have the potential to disperse seeds from intact and degraded forest to adjacent cleared lands, but that direct seed transfer from intact forests is limited, particularly for large-seeded trees. Degraded forests may play a vital role in supporting natural regenerat

  • Journal article
    Ahmadi Y, Umrekar TR, Mutter N, Beeby M, Barišić Iet al., 2024,

    DNA origami-enhanced binding of aptamers to Staphylococcus aureus cells

    , Biosensors and Bioelectronics: X, Vol: 16

    The combination of DNA origami nanostructures and aptamers provides a powerful technology for diagnostic assays. Here, we functionalized a DNA origami nanostructure with a Protein-A binding aptamer to target Staphylococcus aureus bacterial cells. Using an enzyme-linked oligonucleotide assay (ELONA), we semi-quantitatively analyzed and compared the interaction of the aptamer and aptamer-modified DNA origamis with Staphylococcus aureus bacterial isolates. The results showed that aptamer-functionalized DNA nanostructures bind with five times higher affinity (KD: 34 ± 5 nM) compared to the aptamer alone (KD: 160 ± 9 nM). Visualising the interaction of bacterial cells and nanostructures with electron cryotomography further confirmed the aptamer-mediated specific interaction of DNA nanostructures with bacterial cells.

  • Journal article
    Karamanos TK, Matthews S, 2024,

    Biomolecular NMR in the AI-assisted structural biology era: Old tricks and new opportunities.

    , Biochim Biophys Acta Proteins Proteom, Vol: 1872

    Over the last 40 years nuclear magnetic resonance (NMR) spectroscopy has established itself as one of the most versatile techniques for the characterization of biomolecules, especially proteins. Given the molecular size limitations of NMR together with recent advances in cryo-electron microscopy and artificial intelligence-assisted protein structure prediction, the bright future of NMR in structural biology has been put into question. In this mini review we argue the contrary. We discuss the unique opportunities solution NMR offers to the protein chemist that distinguish it from all other experimental or computational methods, and how it can benefit from machine learning.

  • Journal article
    Cretois B, Bick IA, Balantic C, Gelderblom FB, Pávon-Jordán D, Wiel J, Sethi SS, Betchkal DH, Banet B, Rosten CM, Reinen TAet al., 2024,

    Snowmobile noise alters bird vocalization patterns during winter and pre-breeding season

    , Journal of Applied Ecology, Vol: 61, Pages: 340-350, ISSN: 0021-8901

    Noise pollution poses a significant threat to ecosystems worldwide, disrupting animal communication and causing cascading effects on biodiversity. In this study, we focus on the impact of snowmobile noise on avian vocalizations during the non-breeding winter season, a less-studied area in soundscape ecology. We developed a pipeline relying on deep learning methods to detect snowmobile noise and applied it to a large acoustic monitoring dataset collected in Yellowstone National Park. Our results demonstrate the effectiveness of the snowmobile detection model in identifying snowmobile noise and reveal an association between snowmobile passage and changes in avian vocalization patterns. Snowmobile noise led to a decrease in the frequency of bird vocalizations during mornings and evenings, potentially affecting winter and pre-breeding behaviours such as foraging, predator avoidance and successfully finding a mate. However, we observed a recovery in avian vocalizations after detection of snowmobiles during mornings and afternoons, indicating some resilience to sporadic noise events. Synthesis and applications: Our findings emphasize the need to consider noise impacts in the non-breeding season and provide valuable insights for natural resource managers to minimize disturbance and protect critical avian habitats. The deep learning approach presented in this study offers an efficient and accurate means of analysing large-scale acoustic monitoring data and contributes to a comprehensive understanding of the cumulative impacts of multiple stressors on avian communities.

  • Journal article
    Cruz-Silva E, Harrion SP, Prentice IC, Marinova Eet al., 2024,

    Holocene vegetation dynamics of the Eastern Mediterranean region: old controversies addressed by a new analysis

    , Journal of Biogeography, Vol: 51, Pages: 294-310, ISSN: 0305-0270

    Aim:We reconstruct vegetation changes since 12 ky in the Eastern Mediterranean to examine four features of the regional vegetation history that are controversial: the extent of non-analogue vegetation assemblages in the transition from the Late Glacial to the early Holocene, the synchroneity of postglacial forest expansion, the geographical extent of temperate deciduous forest during the mid-Holocene and the timing and trigger for the re-establishment of drought-tolerant vegetation during the late Holocene.Location:The Eastern Mediterranean–Black Sea Caspian Corridor.Taxon:Vascular plants.Methods:We reconstruct vegetation changes for 122 fossil pollen records using a method that accounts for within-biome variability in pollen taxon abundance to determine the biome with which a sample has greatest affinity. Per-biome affinity threshold values were used to identify samples that do not belong to any modern biome. We apply time series analysis and mapping to examine space and time changes.Results:Sites with non-analogue vegetation were most common between 11.5 and 9.5 ky and mostly in the Carpathians. The transition from open vegetation to forest occurred at 10.64 ± 0.65 ky across the whole region. Temperate deciduous forest was not more extensive at 6 ky; maximum expansion occurred between 5.5 and 5 ky. Expansion of forest occurred between c. 4 and 2.8 k, followed by an abrupt decrease and a subsequent recovery. This pattern is not consistent with a systematic decline of forest towards more drought-tolerant vegetation in the late Holocene but is consistent with centennial-scale speleothem patterns linked to variations in moisture availability.Main Conclusions:We show the occurrence of non-analogue vegetation types peaked during early Holocene, forest expansion was synchronous across the region and there was an expansion of moisture-demanding temperate trees around 5.5 to 5 ky. There is no signal of a continuous late Holocene aridificat

  • Journal article
    Leung PB, Matanza XM, Roche B, Ha KP, Cheung HC, Appleyard S, Collins T, Flanagan O, Marteyn BS, Clements Aet al., 2024,

    Shigella sonnei utilises colicins during inter-bacterial competition.

    , Microbiology (Reading), Vol: 170

    The mammalian colon is one of the most densely populated habitats currently recognised, with 1011-1013 commensal bacteria per gram of colonic contents. Enteric pathogens must compete with the resident intestinal microbiota to cause infection. Among these enteric pathogens are Shigella species which cause approximately 125 million infections annually, of which over 90 % are caused by Shigella flexneri and Shigella sonnei. Shigella sonnei was previously reported to use a Type VI Secretion System (T6SS) to outcompete E. coli and S. flexneri in in vitro and in vivo experiments. S. sonnei strains have also been reported to harbour colicinogenic plasmids, which are an alternative anti-bacterial mechanism that could provide a competitive advantage against the intestinal microbiota. We sought to determine the contribution of both T6SS and colicins to the anti-bacterial killing activity of S. sonnei. We reveal that whilst the T6SS operon is present in S. sonnei, there is evidence of functional degradation of the system through SNPs, indels and IS within key components of the system. We created strains with synthetically inducible T6SS operons but were still unable to demonstrate anti-bacterial activity of the T6SS. We demonstrate that the anti-bacterial activity observed in our in vitro assays was due to colicin activity. We show that S. sonnei no longer displayed anti-bacterial activity against bacteria that were resistant to colicins, and removal of the colicin plasmid from S. sonnei abrogated anti-bacterial activity of S. sonnei. We propose that the anti-bacterial activity demonstrated by colicins may be sufficient for niche competition by S. sonnei within the gastrointestinal environment.

  • Journal article
    Chukhutsina VU, Hutchison CDM, van Thor JJ, 2024,

    The Carbonyl Group in β2 of the Carotenoid Tunes the Photocycle Kinetics in Orange Carotenoid Protein

    , Journal of Molecular Biology, Pages: 168463-168463, ISSN: 0022-2836
  • Journal article
    Schuster M, Eisele S, Armas-Egas L, Kessenbrock T, Kourelis J, Kaiser M, van der Hoorn RALet al., 2024,

    Enhanced late blight resistance by engineering an EpiC2B-insensitive immune protease

    , Plant Biotechnology Journal, Vol: 22, Pages: 284-286, ISSN: 1467-7644

    Papain-like immune proteases (PLCPs) are promising engineering targets for crop protection, given their significant roles in plant immunity for key crops such as tomato, maize and citrus (Misas-Villamil et al., 2016). The wide range of pathogen-secreted PLCP inhibitors highlights the importance of these proteases in defending against various pathogens. Depletion of the apoplastic immune PLCP Phytophthora-inhibited protease 1 (Pip1) from tomato, for instance, causes hyper-susceptibility to bacterial, fungal and oomycete tomato pathogens (Ilyas et al., 2015). Immunity by Pip1 in wild-type tomato is, however, suboptimal since Pip1 is suppressed during infection by diverse pathogen-secreted inhibitors, such as the cystatin-like EpiC2B from the oomycete late blight pathogen Phytophthora infestans (Tian et al., 2007). Here, we tested whether we could increase Pip1-based immunity against late blight by engineering Pip1 into an EpiC2B-insensitive protease. To guide Pip1 mutagenesis, we generated a structural model of the EpiC2B-Pip1 complex using AlphaFold-Multimer (Evans et al., 2022). This structural model represents a classic interaction between the tripartite wedge of cystatin (EpiC2B) in the substrate binding groove of papain (Pip1). This model indicated that engineering Pip1 to prevent inhibition without affecting Pip1 substrate specificity is possible because the interaction surface of Pip1 with EpiC2B is larger than the substrate binding groove (Figure 1a).

  • Journal article
    Cantwell-Jones A, Tylianakis J, Larson K, Gill Ret al., 2024,

    Using individual-based trait frequency distributions to forecast plant-pollinator network responses to environmental change

    , Ecology Letters, Vol: 27, ISSN: 1461-023X

    Determining how and why organisms interact is fundamental to understanding ecosystem responses to future environmental change. To assess the impact on plant-pollinator interactions, recent studies have examined how the effects of environmental change on individual interactions accumulate to generate species-level responses. Here, we review recent developments in using plant-pollinator networks of interacting individuals along with their functional traits, where individuals are nested within species nodes. We highlight how these individual-level, trait-based networks connect intraspecific trait variation (as frequency distributions of multiple traits) with dynamic responses within plant-pollinator communities. This approach can better explain interaction plasticity, and changes to interaction probabilities and network structure over spatiotemporal or other environmental gradients. We argue that only through appreciating such trait-based interaction plasticity can we accurately forecast the potential vulnerability of interactions to future environmental change. We follow this with general guidance on how future studies can collect and analyse high-resolution interaction and trait data, with the hope of improving predictions of future plant-pollinator network responses for targeted and effective conservation.

  • Journal article
    Gardner S, Jin Y, Fyfe PK, Voisin T, Bellón JS, Pohler E, Piehler J, Moraga I, Bubeck Det al., 2024,

    Structural insights into IL-11-mediated signalling and human IL6ST variant-associated immunodeficiency

    , Nature Communications, ISSN: 2041-1723
  • Report
    Waring BG, 2024,

    The potential for enhanced soil carbon sequestration to mitigate climate change

    This briefing note assesses the potential for soil carbon sequestration to mitigate climate change, summarising the basic science and providing an overview of best practices for measuring and modifying soil carbon stocks. We also set out recommendations for policy makers, examining UK land use policies as a case study.

  • Journal article
    Pawar S, Huxley PJ, Smallwood TRC, Nesbit ML, Chan AHH, Shocket MS, Johnson LR, Kontopoulos D-G, Cator LJet al., 2024,

    Variation in temperature of peak trait performance constrains adaptation of arthropod populations to climatic warming.

    , Nat Ecol Evol

    The capacity of arthropod populations to adapt to long-term climatic warming is currently uncertain. Here we combine theory and extensive data to show that the rate of their thermal adaptation to climatic warming will be constrained in two fundamental ways. First, the rate of thermal adaptation of an arthropod population is predicted to be limited by changes in the temperatures at which the performance of four key life-history traits can peak, in a specific order of declining importance: juvenile development, adult fecundity, juvenile mortality and adult mortality. Second, directional thermal adaptation is constrained due to differences in the temperature of the peak performance of these four traits, with these differences expected to persist because of energetic allocation and life-history trade-offs. We compile a new global dataset of 61 diverse arthropod species which provides strong empirical evidence to support these predictions, demonstrating that contemporary populations have indeed evolved under these constraints. Our results provide a basis for using relatively feasible trait measurements to predict the adaptive capacity of diverse arthropod populations to geographic temperature gradients, as well as ongoing and future climatic warming.

  • Journal article
    Li S, Waring B, Powers J, Medvigy Det al., 2024,

    Tropical dry forest response to nutrient fertilization: a model validation and sensitivity analysis

    , Biogeosciences, Vol: 21, Pages: 455-471, ISSN: 1726-4170

    Soil nutrients, especially nitrogen (N) and phosphorus (P), regulate plant growth and hence influence carbon fluxes between the land surface and atmosphere. However, how forests adjust biomass partitioning to leaves, wood, and fine roots in response to N and/or P fertilization remains puzzling. Recent work in tropical forests suggests that trees increase fine root production under P fertilization, but it is unclear whether mechanistic models can reproduce this dynamic. In order to better understand mechanisms governing nutrient effects on plant allocation and improve models, we used the nutrient-enabled ED2 model to simulate a fertilization experiment being conducted in a secondary tropical dry forest in Costa Rica. We evaluated how different allocation parameterizations affected model performance. These parameterizations prescribed a linear relationship between relative allocation to fine roots and soil P concentrations. The slope of the linear relationship was allowed to be positive, negative, or zero. Some parameterizations realistically simulated leaf, wood, and fine root production, and these parameterizations all assumed a positive relationship between relative allocation to fine roots and soil P concentration. Model simulations of a 30-year timeframe indicated strong sensitivity to parameterization and fertilization treatment. Without P fertilization, the simulated aboveground biomass (AGB) accumulation was insensitive to the parameterization. With P fertilization, the model was highly sensitive to the parameterization and the greatest AGB accumulation occurred when relative allocation to fine roots was independent of soil P. Our study demonstrates the need for simultaneous measurements of leaf, wood, and fine root production in nutrient fertilization experiments and for longer-term experiments. Models that do not accurately represent allocation to fine roots may be highly biased in their simulations of AGB, especially on multi-decadal timescales.

  • Journal article
    Prentice IC, Keeping T, Harrison SP, 2024,

    Modelling the Daily Probability of Wildfire Occurrence in the Contiguous United States

    , Environmental Research Letters, ISSN: 1748-9326
  • Journal article
    Wan Y, Myall AC, Boonyasiri A, Bolt F, Ledda A, Mookerjee S, Weiße AY, Getino M, Turton JF, Abbas H, Prakapaite R, Sabnis A, Abdolrasouli A, Malpartida-Cardenas K, Miglietta L, Donaldson H, Gilchrist M, Hopkins KL, Ellington MJ, Otter JA, Larrouy-Maumus G, Edwards AM, Rodriguez-Manzano J, Didelot X, Barahona M, Holmes AH, Jauneikaite E, Davies Fet al., 2024,

    Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes.

    , J Infect Dis

    BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

  • Journal article
    Perkins R, Barron L, Glauser G, Whitehead M, Woodward G, Goulson Det al., 2024,

    Down-the-drain pathways for fipronil and imidacloprid applied as spot-on parasiticides to dogs: Estimating aquatic pollution.

    , Sci Total Environ, Vol: 917

    Fipronil and imidacloprid have been widely detected in UK surface waters in recent years, often at concentrations that ecotoxicological studies have shown can harm aquatic life. Down-the-drain (DTD) passage of pet flea and tick treatments are being implicated as an important source, with many of the UK's 22 million cats and dogs receiving routine, year-round preventative doses containing these parasiticides. The UK Water Industry's 3rd Chemical Investigation Programme (UKWIR CIP3) has confirmed wastewater as a major entry pathway for these chemicals into surface waters, but the routes by which they enter the wastewater system remain unclear. We addressed this knowledge gap by conducting the first quantification of DTD emissions from 98 dogs treated with spot-on ectoparasiticides containing fipronil or imidacloprid, through bathing, bed washing and washing of owners' hands. Both chemicals were detected in 100 % of washoff samples, with bathing accounting for the largest emissions per event (up to 16.8 % of applied imidacloprid and 24.5 % of applied fipronil). Modelled to account for the frequency of emitting activities, owner handwashing was identified as the largest source of DTD emissions from the population overall, with handwash emissions occurring for at least 28 days following product application and an estimated 4.9 % of imidacloprid and 3.1 % of fipronil applied in dog spot-ons passing down-the-drain via this route. The normalised daily per capita emissions for all routes combined were 8.7 μg/person/day for imidacloprid and 2.1 μg/person/day for fipronil, equivalent to 20-40 % of the daily per capita load in wastewater, as estimated from UKWIR CIP3 data. Within the current international regulatory framework adhered to by the UK, the environmental exposure of veterinary medicines intended for use in small companion animals is assumed to be low, and DTD pathways are not considered. We recommend a systematic rev

  • Journal article
    Gumbs R, Scott O, Bates R, Böhm M, Forest F, Gray CL, Hoffmann M, Kane D, Low C, Pearse WD, Pipins S, Tapley B, Turvey ST, Jetz W, Owen NR, Rosindell Jet al., 2024,

    Global conservation status of the jawed vertebrate Tree of Life

    , Nature Communications, ISSN: 2041-1723

    Human-driven extinction threatens entire lineages across the Tree of Life. Here we assess the conservation status of jawed vertebrate evolutionary history, using three policy-relevant approaches. First, we calculate an index of threat to overall evolutionary history, showing that we expect to lose 86-150 billion years (11-19%) of jawed vertebrate evolutionary history over the next 50-500 years. Second, we rank jawed vertebrate species by their EDGE scores to identify the highest priorities for species-focused conservation of evolutionary history, finding that chondrichthyans, ray-finned fish and testudines rank highest of all jawed vertebrates. Third, we assess the conservation status of jawed vertebrate families. We found that species within monotypic families are more likely to be threatened and more likely to be in decline than other species. We provide a baseline for the status of families at risk of extinction to catalyse conservation action. This work continues a trend of highlighting neglected groups—such as testudines, crocodylians, amphibians and chondrichthyans—as conservation priorities from a phylogenetic perspective.

  • Journal article
    Yoon S, Bae HE, Hariharan P, Nygaard A, Lan B, Woubshete M, Sadaf A, Liu X, Loland CJ, Byrne B, Guan L, Chae PSet al., 2024,

    Rational Approach to Improve Detergent Efficacy for Membrane Protein Stabilization.

    , Bioconjug Chem

    Membrane protein structures are essential for the molecular understanding of diverse cellular processes and drug discovery. Detergents are not only widely used to extract membrane proteins from membranes but also utilized to preserve native protein structures in aqueous solution. However, micelles formed by conventional detergents are suboptimal for membrane protein stabilization, necessitating the development of novel amphiphilic molecules with enhanced protein stabilization efficacy. In this study, we prepared two sets of tandem malonate-derived glucoside (TMG) variants, both of which were designed to increase the alkyl chain density in micelle interiors. The alkyl chain density was modulated either by reducing the spacer length (TMG-Ms) or by introducing an additional alkyl chain between the two alkyl chains of the original TMGs (TMG-Ps). When evaluated with a few membrane proteins including a G protein-coupled receptor, TMG-P10,8 was found to be substantially more efficient at extracting membrane proteins and also effective at preserving protein integrity in the long term compared to the previously described TMG-A13. This result reveals that inserting an additional alkyl chain between the two existing alkyl chains is an effective way to optimize detergent properties for membrane protein study. This new biochemical tool and the design principle described have the potential to facilitate membrane protein structure determination.

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