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  • Journal article
    Macaulay SJ, Jeppesen E, Riebesell U, Nejstgaard JC, Berger SA, Lewandowska AM, Rico A, Kefford BJ, Vad CF, Costello DM, Wang H, Madge Pimentel I, Ramos J, Gonzalez J, Spilling K, de Senerpont Domis L, Boersma M, Stockenreiter M, Meerhoff M, Vijver MG, Kelly-Quinn M, Beklioglu M, Matias MG, Sswat M, Juvigny-Khenafou NPD, Fink P, Zhang P, Taniwaki RH, Ptacnik R, Langenheder S, Nederstigt TAP, Horvath Z, Piggott JJet al., 2025,

    Addressing grand ecological challenges in aquatic ecosystems: how can mesocosms be used to advance solutions?

    , OIKOS, Vol: 2025, ISSN: 0030-1299
  • Journal article
    Chavez EA, Adkins J, Waring BG, Beard KH, Choi RT, Miller L, Saunders T, Atwood TBet al., 2025,

    Herbivory in a low Arctic wetland alters intraspecific plant root traits with consequences for carbon and nitrogen cycling

    , JOURNAL OF ECOLOGY, Vol: 113, Pages: 1225-1238, ISSN: 0022-0477
  • Journal article
    Vlachou D, Ukegbu CV, Mohamed M, Hoermann A, Qin Y, Kweyamba PA, Lwetoijera DW, Windbichler N, Moore S, Christophides GKet al., 2025,

    Nanobody-mediated targeting of Plasmodium falciparum PfPIMMS43 can block malaria transmission in mosquitoes

    , Communications Biology, Vol: 8, ISSN: 2399-3642

    The transition from ookinete to oocyst is a critical step in the Plasmodium falciparum lifecycle and an important target for malaria transmission-blocking strategies. PfPIMMS43, a surface protein of P. falciparum ookinetes and sporozoites, is critical for this transition and aids the parasite in evading mosquito immune responses. Previous studies demonstrated that polyclonal PfPIMMS43 antibodies reduced P. falciparum infection in Anopheles mosquitoes. Here, building on these findings, we have developed high-affinity single-domain VHH antibodies (nanobodies) derived from llama heavy-chain-only antibodies. We have shown that these nanobodies bind both recombinant and endogenous PfPIMMS43 produced by P. falciparum ookinetes in the mosquito midgut. Importantly, they significantly reduce infection intensity and prevalence of laboratory and field strains of P. falciparum in An. coluzzii and An. gambiae, respectively. Epitope mapping has revealed that the nanobodies target conserved regions in the second half of PfPIMMS43, with homology modelling confirming epitope accessibility. These findings establish PfPIMMS43 as a promising transmission-blocking target. To enhance malaria control and elimination efforts, we propose an innovative strategy in which genetically modified mosquitoes express PfPIMMS43-specific nanobodies in their midguts and spread this trait in wild mosquito populations via gene drive technology.
  • Journal article
    Gao F, Ye F, Buck M, Zhang Xet al., 2025,

    Subunit specialization in AAA+ proteins and substrate unfolding during transcription complex remodeling

    , Proceedings of the National Academy of Sciences, Vol: 122, ISSN: 0027-8424

    Bacterial RNA polymerase (RNAP) is a multisubunit enzyme that copies DNA into RNA in a process known as transcription. Bacteria use σ factors to recruit RNAP to promoter regions of genes that need to be transcribed, with 60% bacteria containing at least one specialized σ factor, σ54. σ54 recruits RNAP to promoters of genes associated with stress responses and forms a stable closed complex that does not spontaneously isomerize to the open state where promoter DNA is melted out and competent for transcription. The σ54-mediated open complex formation requires specific AAA+ proteins (ATPases Associated with diverse cellular Activities) known as bacterial enhancer-binding proteins (bEBPs). We have now obtained structures of new intermediate states of bEBP-bound complexes during transcription initiation, which elucidate the mechanism of DNA melting driven by ATPase activity of bEBPs and suggest a mechanistic model that couples the Adenosine triphosphate (ATP) hydrolysis cycle within the bEBP hexamer with σ54 unfolding. Our data reveal that bEBP forms a nonplanar hexamer with the hydrolysis-ready subunit located at the furthest/highest point of the spiral hexamer relative to the RNAP. ATP hydrolysis induces conformational changes in bEBP that drives a vectoral transiting of the regulatory N terminus of σ54 into the bEBP hexamer central pore causing the partial unfolding of σ54, while forming specific bEBP contacts with promoter DNA. Furthermore, our data suggest a mechanism of the bEBP AAA+ protein that is distinct from the hand-over-hand mechanism proposed for many other AAA+ proteins, highlighting the versatile mechanisms utilized by the large protein family.
  • Journal article
    Verkuijl SAN, Corsano GD, Capriotti P, Yen P-S, Inghilterra MG, Selvaraj P, Hoermann A, Martinez-Sanchez A, Ukegbu CV, Kebede TM, Vlachou D, Christophides GK, Windbichler Net al., 2025,

    A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184

    , Nature Communications, Vol: 16, ISSN: 2041-1723

    Gene drive technology presents a promising approach to controlling malaria vector populations. Suppression drives are intended to disrupt essential mosquito genes whereas modification drives aim to reduce the individual vectorial capacity of mosquitoes. Here we present a highly efficient homing gene drive in the African malaria vector Anopheles gambiae that targets the microRNA gene mir-184 and combines suppression with modification. Homozygous gene drive (miR-184D) individuals incur significant fitness costs, including high mortality following a blood meal, that curtail their propensity for malaria transmission. We attribute this to a role of miR-184 in regulating solute transport in the mosquito gut. However, females remain fully fertile, and pure-breeding miR-184D populations suitable for large-scale releases can be reared under laboratory conditions. Cage invasion experiments show that miR-184D can spread to fixation thereby reducing population fitness, while being able to propagate a separate antimalarial effector gene at the same time. Modelling indicates that the miR-184D drive integrates aspects of population suppression and population replacement strategies into a candidate strain that should be evaluated further as a tool for malaria eradication.
  • Journal article
    Oqua AI, Chao K, El Eid L, Casteller L, Baxter BP, Miguéns-Gómez A, Barg S, Jones B, Bernardino de la Serna J, Rouse SL, Tomas Aet al., 2025,

    Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells

    , eLife, Vol: 13, ISSN: 2050-084X

    G protein-coupled receptors (GPCRs) are integral membrane proteins which closely interact with their plasma membrane lipid microenvironment. Cholesterol is a lipid enriched at the plasma membrane with pivotal roles in the control of membrane fluidity and maintenance of membrane microarchitecture, directly impacting on GPCR stability, dynamics, and function. Cholesterol extraction from pancreatic beta cells has previously been shown to disrupt the internalisation, clustering, and cAMP responses of the glucagon-like peptide-1 receptor (GLP-1R), a class B1 GPCR with key roles in the control of blood glucose levels via the potentiation of insulin secretion in beta cells and weight reduction via the modulation of brain appetite control centres. Here, we unveil the detrimental effect of a high cholesterol diet on GLP-1R-dependent glucoregulation in vivo, and the improvement in GLP-1R function that a reduction in cholesterol synthesis using simvastatin exerts in pancreatic islets. We next identify and map sites of cholesterol high occupancy and residence time on active <jats:italic>vs</jats:italic> inactive GLP-1Rs using coarse-grained molecular dynamics (cgMD) simulations, followed by a screen of key residues selected from these sites and detailed analyses of the effects of mutating one of these, Val229, to alanine on GLP-1R-cholesterol interactions, plasma membrane behaviours, clustering, trafficking and signalling in INS-1 832/3 rat pancreatic beta cells and primary mouse islets, unveiling an improved insulin secretion profile for the V229A mutant receptor. This study (1) highlights the role of cholesterol in regulating GLP-1R responses in vivo; (2) provides a detailed map of GLP-1R - cholesterol binding sites in model membranes; (3) validates their functional relevance in beta cells; and (4) highlights their potential as locations for the rational design of novel allosteric modulators with the capacity to fine-tune GLP-1R responses.
  • Journal article
    Ishimoto N, Wong JLC, He S, Shirran S, Wright-Paramio O, Seddon C, Singh N, Balsalobre C, Sonani RR, Clements A, Egelman EH, Frankel G, Beis Ket al., 2025,

    Cryo-EM structure of the conjugation H-pilus reveals the cyclic nature of the TrhA pilin

    , Proceedings of the National Academy of Sciences, Vol: 122, ISSN: 0027-8424

    Conjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F-pilus, are dynamic tubular structures, composed of a polymerized pilin, that mediate the initial donor–recipient interactions, a process known as mating pair formation (MPF). IncH are low-copy-number plasmids, traditionally considered broad host range, which are found in bacteria infecting both humans and animals. The reference IncHI1 plasmid R27, isolated from Salmonella enterica serovar Typhi, encodes the conjugative H-pilus subunit TrhA containing 74 residues after cleavage of the signal sequence. Here, we show that the H-pilus forms long filamentous structures that mediate MPF and describe its cryoelectron-microscopic (cryo-EM) structure at 2.2 Å resolution. Like the F pilus, the H-pilin subunits form helical assemblies with phospholipid molecules at a stoichiometric ratio of 1:1. While there were previous reports that the T-pilus from Agrobacterium tumefaciens was composed of cyclic subunits, three recent cryo-EM structures of the T-pilus found no such cyclization. Here, we report that the H-pilin is cyclic, with a covalent bond connecting the peptide backbone between the N and C termini. Both the cryo-EM map and mass spectrometry revealed cleavage of the last five residues of the pilin, followed by cyclization via condensation of the amine and carboxyl residues. Mutagenesis experiments revealed that loss of cyclization abolished pilus biogenesis and efficient plasmid transfer. The cyclic nature of the pilin could stabilize the pilus and may explain the high incidence of IncH plasmid dissemination.
  • Journal article
    Yang J, Yang C, Lin H-W, Lees AC, Tobias JAet al., 2025,

    Elevational constraints on flight efficiency shape global gradients in avian wing morphology

    , Current Biology, Vol: 35, Pages: 1890-1900.e5, ISSN: 0960-9822

    Wings with an elongated shape or larger surface area are associated with increased flight efficiency in a wide range of animals from insects to birds.1,2,3,4 Inter- and intra-specific variation in these attributes of wing shape is determined by a range of factors—including foraging ecology, migration, and climatic seasonality5,6,7,8—all of which may drive latitudinal gradients in wing morphology.9,10 A separate hypothesis predicts that wing shape should also follow an elevational gradient5,11 because air density declines with altitude,12 altering the aerodynamics of flight and driving the evolution of more efficient wings in high-elevation species to compensate for reduced lift.13,14,15 Although previous analyses have shown a tendency for longer or larger wings at higher elevations, at least locally,16,17,18,19,20 it is difficult to rule out a range of alternative explanations since we currently lack a global synthesis of elevational gradients in wing shape for any taxonomic group. In this study, we use phylogenetic models to explore elevational effects on metrics of wing morphology linked to aerodynamic function in 9,982 bird species while simultaneously controlling for multiple climatic factors and ecological attributes of species. We found that relative wing elongation (hand-wing index) and wing area increase with elevation, even when accounting for latitude, temperature seasonality, body mass, habitat, aerial lifestyle, and altitudinal migration. These results confirm a pervasive elevational gradient in avian wing morphology and suggest that aerodynamic constraints linked to air density, perhaps coupled with oxygen deficiency, contribute to global patterns of trait evolution in flying animals.
  • Journal article
    Keeping TR, ZHOU B, Cai W, Shepherd TG, Prentice IC, Van Der Wiel K, Harrison Set al., 2025,

    Present and future interannual variability in wildfire occurrence: a large ensemble application to the United States

    , Frontiers in Forests and Global Change, Vol: 8, ISSN: 2624-893X

    Realistic projections of future wildfires need to account for both the stochastic nature of climate and the randomness of individual fire events. Here we adopt a probabilistic approach to predict current and future fire probabilities using a large ensemble of 1,600 modelled years representing different stochastic realisations of the climate during a modern reference period (2000–2009) and a future characterised by an additional 2°C global warming. This allows us to characterise the distribution of fire years for the contiguous United States, including extreme years when the number of fires or the length of the fire season exceeded those seen in the short observational record. We show that spread in the distribution of fire years in the reference period is higher in areas with a high mean number of fires, but that there is variation in this relationship with regions of proportionally higher variability in the Great Plains and southwestern United States. The principal drivers of variability in simulated fire years are related either to interannual variability in fuel production or atmospheric moisture controls on fuel drying, but there are distinct geographic patterns in which each of these is the dominant control. The ensemble also shows considerable spread in fire season length, with regions such as the southwestern United States being vulnerable to very long fire seasons in extreme fire years. The mean number of fires increases with an additional 2°C warming, but the spread of the distribution increases even more across three quarters of the contiguous United States. Warming has a strong effect on the likelihood of less fire-prone regions of the northern United States to experience extreme fire years. It also has a strong amplifying effect on annual fire occurrence and fire season length in already fire-prone regions of the western United States. The area in which fuel availability is the dominant control on fire occurrence increases substantially wit
  • Journal article
    Youn T, Kim G, Hariharan P, Li X, Ahmed W, Byrne B, Liu X, Guan L, Chae PSet al., 2025,

    Improved pendant-bearing glucose-neopentyl glycols for membrane protein stability

    , Bioconjugate Chemistry, Vol: 36, Pages: 707-717, ISSN: 1043-1802

    Membrane proteins are biologically and pharmaceutically significant, and determining their 3D structures requires a membrane-mimetic system to maintain protein stability. Detergent micelles are widely used as membrane mimetics; however, their dynamic structures often lead to the denaturation and aggregation of encapsulated membrane proteins. To address the limitations of classical detergents in stabilizing membrane proteins, we previously reported a class of glucose-neopentyl glycols (GNGs) and their pendant-bearing versions (P-GNGs), several of which proved more effective than DDM in stabilizing membrane proteins. In this study, we synthesized additional GNG derivatives by varying the lengths of the pendant (P-GNGs), and by introducing hemifluorinated pendants to the GNG scaffold (fluorinated pendant-bearing GNGs or FP-GNGs). The synthetic flexibility of the GNG chemical architecture allowed us to create a diverse range of derivatives, essential for the effective optimization of detergent properties. When tested with two model membrane proteins (a transporter and a G-protein coupled receptor (GPCR)), most of the new (F)P-GNGs demonstrated superior stabilization of these membrane proteins compared to DDM, the original GNG (OGNG)), and a previously developed P-GNG (i.e., GNG-3,14). Notably, several P-GNGs synthesized in this study were as effective as or even better than lauryl maltose neopentyl glycol (LMNG) in stabilizing a human GPCR, beta2 adrenergic receptor (β2AR). Enhanced protein stability was particularly observed for the P-GNGs with a butyl (C4) or pentyl (C5) pendant, indicating that these pendant sizes are optimal for membrane protein stability. The volumes of these pendants appear to minimize the empty spaces in the micelle interiors, thereby enhancing detergent-detergent interactions in micelles complexed with the membrane proteins. Additionally, we identified one FP-GNG that was more efficient at extracting the transporter and more effective at st
  • Journal article
    Alonso A, Endres RG, Kirkegaard JB, 2025,

    Local Clustering and Global Spreading of Receptors for Optimal Spatial Gradient Sensing

    , PHYSICAL REVIEW LETTERS, Vol: 134, ISSN: 0031-9007
  • Journal article
    Sadaf A, Yun HS, Lee H, Stanfield S, Lan B, Salomon K, Woubshete M, Kim S, Ehsan M, Bae H, Byrne B, Loland CJ, Liu X, Guan L, Im W, Chae PSet al., 2025,

    Multiple pendants-bearing triglucosides for membrane protein studies: effects of pendant length and number on micelle interior hydration and protein stability

    , Biomacromolecules, Vol: 26, Pages: 2565-2579, ISSN: 1525-7797

    Membrane proteins play central roles in cell physiology and are the targets of over 50% of FDA-approved drugs. In the present study, we prepared single alkyl-chained triglucosides decorated with multiple pendants, designated multiple pendant-bearing glucosides (MPGs), to enhance membrane protein stability. The new detergents feature two and four pendants of varying size at the hydrophilic–lipophilic interfaces, designated MPG-Ds and MPG-Ts, respectively. When tested with model membrane proteins, including the human adrenergic receptor (β2AR), the tetra-pendant-bearing MPGs (MPG-Ts) demonstrated superior performance compared to the dipendant analogs (MPG-Ds) and the gold standard DDM. All-atom molecular dynamics (MD) simulations results reveal that the four-pendant configuration of this detergent is remarkably effective in excluding water from the hydrophobic micelle interiors compared to the dipendant MPGs and DDM, an unprecedented feature of this new detergent. Our findings provide a novel strategy for designing water-resistant detergents, advancing the field of membrane protein research.
  • Journal article
    Davydova S, Liu J, Liu Y, Prince K, Mann J, Kandul NP, Braswell WE, Champer J, Akbari OS, Meccariello Aet al., 2025,

    A self-limiting sterile insect technique alternative for Ceratitis capitata

    , BMC Biology, Vol: 23, ISSN: 1741-7007

    BackgroundGenetic biocontrol systems have broad applications in population control of insects implicated in both disease spread and food security. Ceratitis capitata (the Mediterranean fruit fly), a major agricultural pest with a global distribution, is one of the appealing targets for such genetic control.ResultsIn this study, we establish and characterise a novel split-CRISPR/Cas9 system we term Sex Conversion Induced by CRISPR (SCIC) in C. capitata. Using the white eye gene for toolkit selection we achieved up to 100% CRISPR/Cas9 efficiency, displaying the feasibility of C. capitata split-CRISPR/Cas9 systems using constitutive promoters. We then induce sex conversion by targeting the transformer gene in a SCIC approach aimed for SIT-mediated releases upon radiation-based sterilisation. Knock-out of transformer induced partial to full female-to-male sex conversion, with the remaining individuals all being intersex and sterile. SCIC population modelling shows a strong potential to outcompete traditional SIT, allowing for faster population elimination with fewer released sterile males.ConclusionOverall, we construct an appropriate CRISPR/Cas9 toolkit for the use in C capitata. Our results build the foundation for further genetic pest control methods in the species and related tephritid agricultural pests.
  • Journal article
    Rocco C, Suzuki M, Vilar R, Garcia-España E, Blasco S, Larrouy-Maumus G, Turnbull C, Wissuwa M, Cao X, Weiss Det al., 2025,

    Enhancing zinc bioavailability in rice using the novel synthetic siderophore ligand proline-2′-deoxymugineic acid (PDMA): critical insights from metal binding studies and geochemical speciation modeling

    , Journal of Agricultural and Food Chemistry, Vol: 73, Pages: 8243-8253, ISSN: 0021-8561

    Bioavailable ligands that bind metals mediate their uptake in plants, leading to the study of artificial ligands as potential fertilizers. Proline-2′-deoxymugineic acid (PDMA) has shown a high affinity for FeIII, enhancing iron uptake in rice and suggesting that it could be used for improving zinc uptake. This work studied chemical solution parameters, i.e., redox potential, ion strength, pH, and ligand/metal concentrations controlling ZnII–PDMA complex formation in rice-producing soils using geochemical speciation modeling. We show that PDMA is generally selective for ZnII in reducing, saline, and alkaline soil solutions. Comparison with a recent micronutrient uptake study in rice suggests that free PDMA should be added in reducing conditions to avoid competition with CuII and FeIII or as the ZnII–PDMA complex at pH below 9. The Zn/M ratios (M = CuII, FeIII) needed to form stable ZnII–PDMA complexes were also identified. This study shows the promise of PDMA as a fertilizer to overcome zinc deficiencies in alkaline and flooded soils.
  • Journal article
    Davydova S, Yu D, Meccariello A, 2025,

    Genetic engineering for SIT application: a fruit fly-focused review

    , INSECT SCIENCE, ISSN: 1672-9609
  • Journal article
    Cooke R, Outhwaite CL, Bladon AJ, Millard J, Rodger JG, Dong Z, Dyer EE, Edney S, Murphy JF, Dicks LV, Hui C, Jones JI, Newbold T, Purvis A, Roy HE, Woodcock BA, Isaac NJBet al., 2025,

    Integrating multiple evidence streams to understand insect biodiversity change

    , SCIENCE, Vol: 388, ISSN: 0036-8075
  • Journal article
    Feleke R, Jogaudaite S, Velentza-Almpani E, Yeung-Yeung L, Clode D, Ko JH, Shin B, Matthews S, Otero-Jimenez M, Wojewska MJ, Gray-Rodriguez S, Marzi SJ, Spires-Jones MP, Spires-Jones TL, Johnson MR, Alegre-Abarrategui Jet al., 2025,

    Seeding-competent early tau multimers are associated with cell type-specific transcriptional signatures

    , Acta Neuropathologica, Vol: 149, ISSN: 1432-0533

    The initial molecular alterations of Alzheimer’s disease (AD) are unknown. Established AD is characterized by profound structural and transcriptional alterations in the human brain, with the hallmark neuropathological features being beta-amyloid (Aβ) accumulation in senile plaques and hyperphosphorylated fibrillar tau in neurofibrillary tangles (NFTs). Previous evidence indicates that tau multimerization into small aggregates is one of the earliest molecular alterations, anticipating the accumulation of hyperphosphorylated tau in NFTs. In this study, we investigated the seeding capacity of these early small tau multimers and the transcriptional changes associated with them, aiming to unveil early pathogenic processes in AD-type tau pathology. Early tau multimers visualized with tau proximity ligation assay (tau-PLA) in the post-mortem temporal cortex demonstrated high seeding activity detected by real-time quaking-induced conversion (RT-QuIC) assay and induction of aggregates in a tau biosensor cell line. Using single-nucleus transcriptomics, we showed that brain tissue harboring seeding-competent early tau multimers, but without significant NFT pathology, is associated with substantial gene expression alterations across diverse cell types when compared to control tissue lacking either multimers or NFTs. Differentially expressed genes, such as APP, MAPT, and PSEN1, exhibited significant enrichment of AD heritability in up-regulated genes within excitatory neurons, astrocytes, and oligodendrocytes. Pseudotime analysis exposed a positive correlation between the progression of tau pathology and the expression of genes marking reactive astrocytes. In summary, our results support the hypothesis that seeding-competent tau multimerization may initiate AD-type tau pathology cascades before the accumulation of tau in NFTs. This research contributes valuable insights into the early molecular events associated with AD, with implications for future diagnostic and the
  • Journal article
    Gallagher K, Strobl MAR, Anderson ARA, Maini PKet al., 2025,

    Deriving Optimal Treatment Timing for Adaptive Therapy: Matching the Model to the Tumor Dynamics.

    , medRxiv

    Adaptive therapy (AT) protocols have been introduced to combat drug-resistance in cancer, and are characterized by breaks in maximum tolerated dose treatment (the current standard of care in most clinical settings). These breaks are scheduled to maintain tolerably high levels of tumor burden, employing competitive suppression of treatment-resistant sub-populations by treatment-sensitive sub-populations. AT has been integrated into several ongoing or planned clinical trials, including treatment of metastatic castrate-resistant prostate cancer, ovarian cancer, and BRAF-mutant melanoma, with initial clinical results suggesting that it can offer significant extensions in the time to progression over the standard of care. However, these clinical protocols may be sub-optimal, as they fail to account for variation in tumor dynamics between patients, and result in significant heterogeneity in patient outcomes. Mathematical modeling and analysis have been proposed to optimize adaptive protocols, but they do not account for clinical restrictions, most notably the discrete time intervals between the clinical appointments where a patient's tumor burden is measured and their treatment schedule is re-evaluated. We present a general framework for deriving optimal treatment protocols which account for these discrete time intervals, and derive optimal schedules for a number of models to avoid model-specific personalization. We identify a trade-off between the frequency of patient monitoring and the time to progression attainable, and propose an AT protocol based on a single treatment threshold. Finally, we identify a subset of patients with qualitatively different dynamics that instead require a novel AT protocol based on a threshold that changes over the course of treatment.
  • Journal article
    Alzheimer M, Froschauer K, Svensson SL, König F, Hopp E, Drobnič T, Henderson LD, Ribardo DA, Hendrixson DR, Bischler T, Beeby M, Sharma CMet al., 2025,

    Functional genomics of Campylobacter -host interactions in an intestinal tissue model reveals a small lipoprotein essential for flagellar assembly.

    , bioRxiv

    Campylobacter jejuni is currently the most common cause of bacterial gastroenteritis worldwide. However, its genome provides few clues about how it interacts with the host. Moreover, infection screens have often been limited to classical cell culture or animal models. To identify C. jejuni genes involved in host cell interactions, we applied transposon sequencing in a humanized 3D intestinal infection model based on tissue engineering. This revealed key proteins required for host cell adherence and/or internalization, including an Rrf2 family transcriptional regulator as well as three so far uncharacterized genes ( pflC / Cj1643 , pflD / Cj0892c , pflE / Cj0978c ), which we demonstrate to encode factors essential for motility. Deletion mutants of pflC / D / E are non-motile but retain intact, paralysed flagella filaments. We demonstrate that two of these newly identified motility proteins, PflC and PflD, are components of the C. jejuni 's periplasmic disk structures of the high torque motor. The third gene, pflE , encodes a small protein of only 57 aa. Using CryoET imaging we uncovered that the small protein has a striking effect on motor biogenesis, leading to a complete loss of the flagellar disk and motor structures upon its deletion. While PflE does not appear to be a structural component of the motor itself, our data suggests that it is a lipoprotein and supports localization of the main basal disk protein FlgP, which is the first assembly step of the flagellar disk structure. Despite being annotated as a lipoprotein, we find that C. jejuni FlgP instead relies on PflE for its association with the outer membrane. Overall, our genome-wide screen revealed novel C. jejuni host interaction factors including a transcriptional regulator as well as two structural components and a small protein crucial for biogenesis of the C. jejuni high torque flagella motor. Since the flagella machinery is a critical virulence determining factor for C. jejuni , our work demonstrates
  • Journal article
    Weeks BC, Harvey C, Tobias JA, Sheard C, Zhou Z, Fouhey DFet al., 2025,

    Longer wing bones in warmer climates suggest a role of thermoregulation in bird wing evolution

    , Global Ecology and Biogeography, Vol: 34, ISSN: 1466-822X

    AimThe tendency for animals in warmer climates to be longer-limbed (Allen's Rule) is widely attributed to the demands of thermoregulation. The role of thermoregulation in structuring bird wings, however, has been overshadowed by the selective demands placed on wings by flight. We test whether occurrence in warmer climates is associated with longer wing bones.LocationGlobal.Time PeriodCurrent.Major Taxa StudiedAves: Passeriformes.MethodsUsing computer vision, we measure wing-bone length from photographs of museum skeletal specimens for 1520 species of passerine birds. We then model the relationship between wing-bone length and temperature, accounting for allometry, the demands of flight efficiency and manoeuvrability, and a range of ecological and environmental variables.ResultsWing bones are longer in warmer climates. Our models, largely as a result of allometric effects, explain nearly all the variation in wing-bone length in our data, with a marginal R2 = 0.80 and a conditional R2 > 0.99.Main ConclusionsAcross 1520 species of birds, higher temperatures are associated with longer wing bones, as predicted by Allen's Rule. The vascularised musculature along these bones is maximally uncovered when birds actively hold their wings away from their bodies to aid in cooling or during flight. Conversely, the musculature along the wing bones is insulated by feathering when at rest, such that wings play a minor role in heat exchange when individuals are less active and may need to retain heat. While our analyses do not directly establish the mechanistic basis underlying the pattern we recover, given the asymmetry in the role of wings in thermoregulation, we interpret the positive relationship between temperature and wing-bone length to reflect increased demand for heat dissipation in warmer climates. Our findings highlight the role of thermoregulation in shaping even the most critical features of vertebrate anatomy.
  • Journal article
    Flintham E, Savolainen V, Otto S, Reuter M, Mullon Cet al., 2025,

    The maintenance of genetic polymorphism underlyingsexually antagonistic traits

    , Evolution Letters, Vol: 9, Pages: 259-272, ISSN: 2056-3744

    Selection often favours different trait values in males and females, leading to genetic conflicts between the sexes when traits have a shared genetic basis. Such sexual antagonism has beenproposed to maintain genetic polymorphism. However, this notion is based on insights from population genetic models of single loci with fixed fitness effects. It is thus unclear how readily polymorphism emerges from sex-specific selection acting on continuous traits, where fitness effects arisefrom the genotype-phenotype map and the fitness landscape. Here we model the evolution of a continuous trait that has a shared genetic basis but different optima in males and females, considering a wide variety of genetic architectures and fitness landscapes. For autosomal loci, the long-termmaintenance of polymorphism requires strong conflict between males and females that generatesuncharacteristic sex-specific fitness patterns. Instead, more plausible sex-specific fitness landscapestypically generate stabilising selection leading to an evolutionarily stable state that consists of a singlehomozygous genotype. Except for sites tightly linked to the sex determining region, our results indicate that genetic variation due to sexual antagonism should arise only rarely and often be transient,making these signatures challenging to detect in genomic data.
  • Journal article
    Liang G, Sun P, Waring BG, Fu Z, Reich PBet al., 2025,

    Alleviating nitrogen and phosphorus limitation does not amplify potassium‐induced increase in terrestrial biomass

    , Global Change Biology, Vol: 31, ISSN: 1354-1013

    Potassium (K) is the second most abundant nutrient element in plants after nitrogen (N), and has been shown to limit aboveground production in some contexts. However, the role of N and phosphorus (P) availability in mediating K limitation in terrestrial production remains poorly understood; and it is unknown whether K also limits belowground carbon (C) stocks, which contain at least three times more C than those aboveground stocks. By synthesizing 779 global paired observations (528, 125, and 126 for aboveground productivity, root biomass, and soil organic C [SOC], respectively), we found that K addition significantly increased aboveground production and SOC by 8% and 5%, respectively, but did not significantly affect root biomass (+9%). Moreover, enhanced N and/or P availability (through N and P addition) did not further amplify the positive effect of K on aboveground productivity. In other words, K had a positive effect on aboveground productivity only when N and/or P were limiting, indicating that K could somehow substitute for N or P when they were limiting. Climate variables mostly explained the variations in K effects; specifically, stronger positive responses of aboveground productivity and SOC to K were found in regions with high mean annual temperature and wetness. Our results suggest that K addition enhances C sequestration by increasing both aboveground productivity and SOC, contributing to climate mitigation, but the positive effects of K on terrestrial C stocks are not further amplified when N and P limitations are alleviated.
  • Journal article
    Franks N, Wisden W, 2025,

    Reply to: A curious concept of CNS clearance

    , Nature Neuroscience, Vol: 28, Pages: 734-736, ISSN: 1097-6256
  • Journal article
    Chan AHH, Putra P, Schupp H, Koechling J, Strassheim J, Renner B, Schroeder J, Pearse WD, Nakagawa S, Burke T, Griesser M, Meltzer A, Lubrano S, Kano Fet al., 2025,

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

    , METHODS IN ECOLOGY AND EVOLUTION, Vol: 16, Pages: 760-774, ISSN: 2041-210X
  • Journal article
    Christophides GK, 2025,

    Malaria vectors with leaky guts Vector biology

    , NATURE MICROBIOLOGY, Vol: 10, Pages: 817-818, ISSN: 2058-5276
  • Journal article
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