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  • Journal article
    Fallesen T, Amerteifio S, Pruessner G, Jensen H, Sena Get al., 2024,

    Intermittent cell division dynamics in regenerating Arabidopsis roots reveals complex long-range interactions

    , Quantitative Plant Biology, Vol: 5, ISSN: 2632-8828

    In this work, we present a quantitative comparison of the cell division dynamics between populations of intact and regenerating root tips in the plant model system Arabidopsis thaliana. To achieve the required temporal resolution and to sustain it for the duration of the regeneration process, we adopted a live imaging system based on light-sheet fluorescence microscopy, previously developed in the laboratory. We offer a straightforward quantitative analysis of the temporal and spatial patterns of cell division events showing a statistically significant difference in the frequency of mitotic events and spatial separation of mitotic event clusters between intact and regenerating roots.
  • Journal article
    Casadio R, Mathews DH, Sternberg MJE, 2024,

    Computational Resources for Molecular Biology 2024

    , Journal of Molecular Biology, Vol: 436, ISSN: 0022-2836
  • Journal article
    Cioccolo S, Barritt JD, Pollock N, Hall Z, Babuta J, Sridhar P, Just A, Morgner N, Dafforn T, Gould I, Byrne Bet al., 2024,

    The mycobacterium lipid transporter MmpL3 is dimeric in detergent solution, SMALPs and reconstituted nanodiscs

    , RSC Chemical Biology, Vol: 5, Pages: 901-913, ISSN: 2633-0679

    The mycobacterial membrane protein large 3 (MmpL3) transports key precursor lipids to the outer membrane of Mycobacterium species. Multiple structures of MmpL3 from both M. tuberculosis and M. smegmatis in various conformational states indicate that the protein is both structurally and functionally monomeric. However, most other resistance, nodulation and cell division (RND) transporters structurally characterised to date are either dimeric or trimeric. Here we present an in depth biophysical and computational analysis revealing that MmpL3 from M. smegmatis exists as a dimer in a variety of membrane mimetic systems (SMALPs, detergent-based solution and nanodiscs). Sucrose gradient separation of MmpL3 populations from M. smegmatis, reconstituted into nanodiscs, identified monomeric and dimeric populations of the protein using laser induced liquid bead ion desorption (LILBID), a native mass spectrometry technique. Preliminary cryo-EM analysis confirmed that MmpL3 forms physiological dimers. Untargeted lipidomics experiments on membrane protein co-purified lipids revealed PE and PG lipid classes were predominant. Molecular dynamics simulations, in the presence of physiologically-relevant lipid compositions revealed the likely dimer interface.
  • Conference paper
    Mazza T, Roumeliotis TI, Garitta E, Drew D, Rashid ST, Indiveri C, Choudhary JS, Linton KJ, Beis Ket al., 2024,

    Unveiling the Modulation of MRP2 Activity: Insights from Phosphorylation and Drug Interactions

    , 22nd European Bioenergetics Conference (EBEC), Publisher: ELSEVIER, Pages: 84-85, ISSN: 0005-2728
  • Conference paper
    Zhao Z, Vercellino I, Nixon PJ, Sazanov LAet al., 2024,

    Structural analysis of dimeric photosystem II complexes

    , 22nd European Bioenergetics Conference (EBEC), Publisher: ELSEVIER, Pages: 52-52, ISSN: 0005-2728
  • Journal article
    Patel R, Taylor JL, Dickenson AH, McMahon SB, Bannister Ket al., 2024,

    A back-translational study of descending interactions with the induction of hyperalgesia by high-frequency electrical stimulation in rats and humans.

    , Pain, Vol: 165, Pages: 1978-1989

    In humans and animals, high-frequency electrocutaneous stimulation (HFS) induces an "early long-term potentiation-like" sensitisation, where synaptic plasticity is underpinned by an ill-defined interaction between peripheral input and central modulatory processes. The relative contributions of these processes to the initial pain or nociceptive response likely differ from those that underpin development of the heightened response. To investigate the impact of HFS-induced hyperalgesia on pain and nociception in perception and neural terms, respectively, and to explore the impact of descending inhibitory pathway activation on the development of HFS-induced hyperalgesia, we performed parallel studies utilising identical stimuli to apply HFS concurrent to (1) a conditioned pain modulation paradigm during psychophysical testing in healthy humans or (2) a diffuse noxious inhibitory controls paradigm during in vivo electrophysiological recording of spinal neurones in healthy anaesthetised rats. High-frequency electrocutaneous stimulation alone induced enhanced perceptual responses to pinprick stimuli in cutaneous areas secondary to the area of electrical stimulation in humans and increased the excitability of spinal neurones which exhibited stimulus intensity-dependent coded responses to pinprick stimulation in a manner that tracked with human psychophysics, supporting their translational validity. Application of a distant noxious conditioning stimulus during HFS did not alter perceived primary or secondary hyperalgesia in humans or the development of primary or secondary neuronal hyperexcitability in rats compared with HFS alone, suggesting that, upon HFS-response initiation in a healthy nervous system, excitatory signalling escapes inhibitory control. Therefore, in this model, dampening facilitatory mechanisms rather than augmenting top-down inhibitions could prevent pain development.
  • Journal article
    Flo V, Joshi J, Sabot M, Sandoval D, Prentice ICet al., 2024,

    Incorporating photosynthetic acclimation improves stomatal optimisation models

    , Plant, Cell and Environment, Vol: 47, Pages: 3478-3493, ISSN: 0140-7791

    Stomatal opening in plant leaves is regulated through a balance of carbon and water exchange under different environmental conditions. Accurate estimation of stomatal regulation is crucial for understanding how plants respond to changing environmental conditions, particularly under climate change. A new generation of optimality-based modelling schemes determines instantaneous stomatal responses from a balance of trade-offs between carbon gains and hydraulic costs, but most such schemes do not account for biochemical acclimation in response to drought. Here, we compare the performance of six instantaneous stomatal optimisation models with and without accounting for photosynthetic acclimation. Using experimental data from 37 plant species, we found that accounting for photosynthetic acclimation improves the prediction of carbon assimilation in a majority of the tested models. Photosynthetic acclimation contributed significantly to the reduction of photosynthesis under drought conditions in all tested models. Drought effects on photosynthesis could not accurately be explained by the hydraulic impairment functions embedded in the stomatal models alone, indicating that photosynthetic acclimation must be considered to improve estimates of carbon assimilation during drought.
  • Journal article
    Jeong S, Ryu Y, Gentine P, Lian X, Fang J, Li X, Dechant B, Kong J, Choi W, Jiang C, Keenan TF, Harrison SP, Prentice ICet al., 2024,

    Persistent global greening over the last four decades using novel long-term vegetation index data with enhanced temporal consistency

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

    Advanced Very High-Resolution Radiometer (AVHRR) satellite observations have provided the longest global daily records from 1980s, but the remaining temporal inconsistency in vegetation index datasets has hindered reliable assessment of vegetation greenness trends. To tackle this, we generated novel global long-term Normalized Difference Vegetation Index (NDVI) and Near-Infrared Reflectance of vegetation (NIRv) datasets derived from AVHRR and Moderate Resolution Imaging Spectroradiometer (MODIS). We addressed residual temporal inconsistency through three-step post processing including cross-sensor calibration among AVHRR sensors, orbital drifting correction for AVHRR sensors, and machine learning-based harmonization between AVHRR and MODIS. After applying each processing step, we confirmed the enhanced temporal consistency in terms of detrended anomaly, trend and interannual variability of NDVI and NIRv at calibration sites. Our refined NDVI and NIRv datasets showed a persistent global greening trend over the last four decades (NDVI: 0.0008 yr−1; NIRv: 0.0003 yr−1), contrasting with those without the three processing steps that showed rapid greening trends before 2000 (NDVI: 0.0017 yr−1; NIRv: 0.0008 yr−1) and weakened greening trends after 2000 (NDVI: 0.0004 yr−1; NIRv: 0.0001 yr−1). These findings highlight the importance of minimizing temporal inconsistency in long-term vegetation index datasets, which can support more reliable trend analysis in global vegetation response to climate changes.
  • 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
    Roberts C, Flintrop CM, Khachikyan A, Milucka J, Munn CB, Iversen MHet al., 2024,

    Microplastics may reduce the efficiency of the biological carbon pump by decreasing the settling velocity and carbon content of marine snow

    , LIMNOLOGY AND OCEANOGRAPHY, Vol: 69, Pages: 1918-1928, ISSN: 0024-3590
  • Journal article
    Willard SJ, Liang G, Adkins S, Foley K, Murray J, Waring Bet al., 2024,

    Land use drives the distribution of free, physically protected, and chemically protected soil organic carbon storage at a global scale

    , GLOBAL CHANGE BIOLOGY, Vol: 30, ISSN: 1354-1013
  • Journal article
    Mattioli M, Raele RA, Gautam G, Borucu U, Schaffitzel C, Aulicino F, Berger Iet al., 2024,

    Tuning VSV-G Expression Improves Baculovirus Integrity, Stability and Mammalian Cell Transduction Efficiency

    , VIRUSES-BASEL, Vol: 16
  • Journal article
    Nahman-Averbuch H, Piché M, Bannister K, Coghill RCet al., 2024,

    Involvement of propriospinal processes in conditioned pain modulation

    , Pain, Vol: 165, Pages: 1907-1913, ISSN: 0304-3959
  • Journal article
    Henson SA, Laufkotter C, Leung S, Giering SLC, Palevsky HI, Cavan ELet al., 2024,

    Author Correction: Uncertain response of ocean biological carbon export in a changing world (vol 4,2024, 01516)

    , NATURE GEOSCIENCE, Vol: 17, Pages: 944-944, ISSN: 1752-0894
  • Journal article
    Huang C-Y, Huang Y-S, Sugihara Y, Wang H-Y, Huang L-T, Lopez-Agudelo JC, Chen Y-F, Lin K-Y, Chiang B-J, Toghani A, Kourelis J, Wang C-H, Derevnina L, Wu C-Het al., 2024,

    Subfunctionalization of NRC3 altered the genetic structure of the Nicotiana NRC network

    , PLoS Genetics, Vol: 20, ISSN: 1553-7390

    Nucleotide-binding domain and leucine-rich repeat (NLR) proteins play crucial roles in immunity against pathogens in both animals and plants. In solanaceous plants, activation of several sensor NLRs triggers their helper NLRs, known as NLR-required for cell death (NRC), to form resistosome complexes to initiate immune responses. While the sensor NLRs and downstream NRC helpers display diverse genetic compatibility, molecular evolutionary events leading to the complex network architecture remained elusive. Here, we showed that solanaceous NRC3 variants underwent subfunctionalization after the divergence of Solanum and Nicotiana, altering the genetic architecture of the NRC network in Nicotiana. Natural solanaceous NRC3 variants form three allelic groups displaying distinct compatibilities with the sensor NLR Rpi-blb2. Ancestral sequence reconstruction and analyses of natural and chimeric variants identified six key amino acids involved in sensor-helper compatibility. These residues are positioned on multiple surfaces of the resting NRC3 homodimer, collectively contributing to their compatibility with Rpi-blb2. Upon activation, Rpi-blb2-compatible NRC3 variants form membrane-associated punctate and high molecular weight complexes, and confer resistance to the late blight pathogen Phytophthora infestans. Our findings revealed how mutations in NRC alleles lead to subfunctionalization, altering sensor-helper compatibility and contributing to the increased complexity of the NRC network.
  • Journal article
    Heath BE, Suzuki R, LePenru NP, Skinner J, Orme CDL, Ewers RM, Sethi SS, Picinali Let al., 2024,

    Spatial ecosystem monitoring with a Multichannel Acoustic Autonomous Recording Unit (MAARU)

    , Methods in Ecology and Evolution, Vol: 15, Pages: 1568-1579, ISSN: 2041-210X

    1. Multi-microphone recording adds spatial information to recorded audio with emerging applications in ecosystem monitoring. Specifically placing sounds in space can improve animal count accuracy, locate illegal activity like logging and poaching, track animals to monitor behaviour and habitat use and allow for ‘beamforming’ to amplify sounds from target directions for downstream classification. Studies have shown many advantages of spatial acoustics, but uptake remains limited as the equipment is often expensive, complicated, inaccessible or only suitable for short-term deployments.2. With an emphasis on enhanced uptake and usability, we present a low-cost, open-source, six-channel recorder built entirely from commercially available components which can be integrated into a solar-powered, online system. The MAARU (Multichannel Acoustic Autonomous Recording Unit) works as an independent node in long-term autonomous, passive and/or short-term deployments. Here, we introduce MAARU's hardware and software and present the results of lab and field tests investigating the device's durability and usability.3. MAARU records multichannel audio with similar costs and power demands to equivalent omnidirectional recorders. MAARU devices have been deployed in the United Kingdom and Brazil, where we have shown MAARUs can accurately localise pure tones up to 6 kHz and bird calls as far as 8 m away (±10° range, 100% and >60% of signals, respectively). Louder calls may have even further detection radii. We also show how beamforming can be used with MAARUs to improve species ID confidence scores.4. MAARU is an accessible, low-cost option for those looking to explore spatial acoustics accurately and easily with a single device, and without the formidable expenses and processing complications associated with establishing arrays. Ultimately, the added directional element of the multichannel recording provided by MAARU allows for enhanced recording
  • Journal article
    Wayman JP, Sadler JP, Martin TE, Graham LJ, White HJ, Tobias JA, Matthews TJet al., 2024,

    Unravelling the complexities of biotic homogenization and heterogenization in the British avifauna

    , JOURNAL OF ANIMAL ECOLOGY, Vol: 93, Pages: 1288-1302, ISSN: 0021-8790
  • Journal article
    Lingche H, Miguel-Romero L, Patkowski JB, Alqurainy N, Rocha EPC, Costa TRD, Fillol-Salom A, Penades Jet al., 2024,

    Tail assembly interference is a common strategy in bacterial antiviral defenses

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

    Many bacterial immune systems recognize phage structural components to activate antiviral responses, without inhibiting the function of the phage component. These systems can be encoded in specific chromosomal loci, known as defense islands, and in mobile genetic elements such as prophages and phage-inducible chromosomal islands (PICIs). Here, we identify a family of bacterial immune systems, named Tai (for ‘tail assembly inhibition’), that is prevalent in PICIs, prophages and P4-like phage satellites. Tai systems protect their bacterial host population from other phages by blocking the tail assembly step, leading to the release of tailless phages incapable of infecting new hosts. To prevent autoimmunity, some Tai-positive phages have an associated counter-defense mechanism that is expressed during the phage lytic cycle and allows for tail formation. Interestingly, the Tai defense and counter-defense genes are organized in a non-contiguous operon, enabling their coordinated expression.
  • Journal article
    Moratto E, Tang Z, Bozkurt T, Sena Get al., 2024,

    Reduction of Phytophthora palmivora plant root infection in weak electric fields

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

    The global food security crisis is partly caused by significant crop losses due to pests and pathogens, leading to economic burdens. Phytophthora palmivora, an oomycete pathogen, affects many plantation crops and costs over USD 1 billion each year. Unfortunately, there is currently no prevention plan in place, highlighting the urgent need for an effective solution. P. palmivora produces motile zoospores that respond to weak electric fields. Here, we show that external electric fields can be used to reduce root infection in two plant species. We developed two original essays to study the effects of weak electric fields on the interaction between P. palmivora’s zoospores and roots of Arabidopsis thaliana and Medicago truncatula. In the first configuration, a global artificial electric field is set up to induce ionic currents engulfing the plant roots while, in the second configuration, ionic currents are induced only locally and at a distance from the roots. In both cases, we found that weak ionic currents (250–550 μA) are sufficient to reduce zoospore attachment to Arabidopsis and Medicago roots, without affecting plant health. Moreover, we show that the same configurations decrease P. palmivora mycelial growth in Medicago roots after 24 h. We conclude that ionic currents can reduce more than one stage of P. palmivora root infection in hydroponics. Overall, our findings suggest that weak external electric fields can be used as a sustainable strategy for preventing P. palmivora infection, providing innovative prospects for agricultural crop protection.
  • Journal article
    Geffen AJ, Nash RDM, Fox CJ, 2024,

    How well do connectivity tools agree over the full life cycle? A case study of Irish Sea plaice <i>Pleuronectes platessa</i> Linnaeus, 1758

    , JOURNAL OF FISH BIOLOGY, ISSN: 0022-1112
  • Journal article
    Boyle MJW, Sharp AC, Barclay MV, Chung AYC, Ewers RM, de Rougemont G, Bonebrake TC, Kitching RL, Stork NE, Ashton LAet al., 2024,

    Tropical beetles more sensitive to impacts are less likely to be known to science

    , Current Biology, Vol: 34, Pages: R770-R771, ISSN: 0960-9822

    Insects are posited to be declining globally. This is particularly pertinent in tropical forests, which exhibit both the highest levels of biodiversity and the highest rates of biodiversity loss. However, for the hyper-diverse tropical insects there are scant data available to evidence declines. Understanding tropical insect diversity and its response to environmental change has therefore become a challenge, but it is estimated that 80% of tropical insect species remain undescribed1. Insect biodiversity predictions are based mostly on well-studied taxa and extrapolated to other groups, but no one knows whether resilience to environmental change varies between undescribed and described species. Here, we collected staphylinid beetles from unlogged and logged tropical forests in Borneo and investigated their responses to environmental change. Out of 252 morphospecies collected, 76% were undescribed. Undescribed species showed higher community turnover, reduced abundance and decreased probability of occurrence in logged forests. Thus the unknown components of tropical insect biodiversity are likely more impacted by human-induced environmental change. If these patterns are widespread, how accurate will assessments of insect declines in the tropics be?
  • Journal article
    Morales-Castilla I, Davies TJ, Legault G, Buonaiuto DM, Chamberlain CJ, Ettinger AK, Garner M, Jones FAM, Loughnan D, Pearse WD, Sodhi DS, Wolkovich EMet al., 2024,

    Phylogenetic estimates of species-level phenology improve ecological forecasting

    , NATURE CLIMATE CHANGE, ISSN: 1758-678X
  • Journal article
    Benucci B, Spinello Z, Calvaresi V, Viviani V, Perrotta A, Faleri A, Utrio Lanfaloni S, Pansegrau W, d'Alterio L, Bartolini E, Pinzuti I, Sampieri K, Giordano A, Rappuoli R, Pizza M, Masignani V, Norais N, Maione D, Merola Met al., 2024,

    Neisserial adhesin A (NadA) binds human Siglec-5 and Siglec-14 with high affinity and promotes bacterial adhesion/invasion

    , MBIO, Vol: 15, ISSN: 2150-7511
  • Journal article
    Patin EC, Nenclares P, Hak CCW, Dillon MT, Patrikeev A, Mclaughlin M, Grove L, Foo S, Soliman H, Barata JP, Marsden J, Baldock H, Gkantalis J, Roulstone V, Kyula J, Burley A, Hubbard L, Pedersen M, Smith SA, Clancy-Thompson E, Melcher AA, Ono M, Rullan A, Harrington KJet al., 2024,

    Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy

    , NATURE COMMUNICATIONS, Vol: 15
  • 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 vocalization detection delivers reliable global biodiversity insights

    , Proceedings of the National Academy of Sciences of USA, Vol: 121, ISSN: 0027-8424

    Tracking biodiversity and its dynamics at scale is essential if we are to solve global environmental challenges. Detecting animal vocalizations in passively recorded audio data offers an automatable, inexpensive, and taxonomically broad way to monitor biodiversity. However, the labor and expertise required to label new data and fine-tune algorithms for each deployment is a major barrier. In this study, we applied a pretrained bird vocalization detection model, BirdNET, to 152,376 h of audio comprising datasets from Norway, Taiwan, Costa Rica, and Brazil. We manually listened to a subset of detections for each species in each dataset, calibrated classification thresholds, and found precisions of over 90% for 109 of 136 species. While some species were reliably detected across multiple datasets, the performance of others was dataset specific. By filtering out unreliable detections, we could extract species and community-level insight into diel (Brazil) and seasonal (Taiwan) temporal scales, as well as landscape (Costa Rica) and national (Norway) spatial scales. Our findings demonstrate that, with relatively fast but essential local calibration, a single vocalization detection model can deliver multifaceted community and species-level insight across highly diverse datasets; unlocking the scale at which acoustic monitoring can deliver immediate applied impact.
  • Journal article
    Garcia YR, Marrazzo J, Martinon-Torres F, Workowski K, Giordano G, Pizza M, Sohn W-Yet al., 2024,

    Urgent Need to Understand and Prevent Gonococcal Infection: From the Laboratory to Real-World Context

    , JOURNAL OF INFECTIOUS DISEASES, Vol: 230, Pages: e758-e767, ISSN: 0022-1899
  • Journal article
    Hossain MB, Uchiyama Y, Rajib SA, Rahman A, Takatori M, Tan BJY, Sugata K, Nagashima M, Kawakami M, Ito H, Kumagai R, Sadamasu K, Ogi Y, Kawaguchi T, Tamura T, Fukuhara T, Ono M, Yoshimura K, Satou Yet al., 2024,

    A micro-disc-based multiplex method for monitoring emerging SARS-CoV-2 variants using the molecular diagnostic tool Intelli-OVI

    , COMMUNICATIONS MEDICINE, Vol: 4, ISSN: 2730-664X
  • Journal article
    Iliopoulou M, Bajur AT, McArthur HCW, Gabai M, Coyle C, Ajao F, Köchl R, Cope AP, Spillane KMet al., 2024,

    Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses

    , Biophysical Journal, Vol: 123, Pages: 2282-2300, ISSN: 0006-3495

    Subcapsular sinus macrophages (SSMs) play a key role in immune defense by forming immunological barriers that control the transport of antigens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal center reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro. Here, we used multicolor fluorescence microscopy to identify lymph node-derived SSMs in culture. We focused on the role of SSMs as antigen-presenting cells, and found that their actin cytoskeleton regulates the spatial organization and mobility of multivalent antigens (immune complexes [ICs]) displayed on the cell surface. Moreover, we determined that SSMs are mechanosensitive cells that respond to changes in extracellular matrix rigidity by altering the architecture of the actin cytoskeleton, leading to changes in cell morphology, membrane topography, and IC mobility. Changes to extracellular matrix rigidity also modulate actin remodeling by both SSMs and B cells when they form an immune synapse. This alters synapse duration but not IC internalization nor NF-κB activation in the B cell. Taken together, our data reveal that the mechanical microenvironment may influence B cell responses by modulating physical characteristics of antigen presentation by SSMs.
  • Journal article
    Rogers J, Bajur AT, Salaita K, Spillane KMet al., 2024,

    Mechanical control of antigen detection and discrimination by T and B cell receptors

    , Biophysical Journal, Vol: 123, Pages: 2234-2255, ISSN: 0006-3495

    The adaptive immune response is orchestrated by just two cell types, T cells and B cells. Both cells possess the remarkable ability to recognize virtually any antigen through their respective antigen receptors—the T cell receptor (TCR) and B cell receptor (BCR). Despite extensive investigations into the biochemical signaling events triggered by antigen recognition in these cells, our ability to predict or control the outcome of T and B cell activation remains elusive. This challenge is compounded by the sensitivity of T and B cells to the biophysical properties of antigens and the cells presenting them—a phenomenon we are just beginning to understand. Recent insights underscore the central role of mechanical forces in this process, governing the conformation, signaling activity, and spatial organization of TCRs and BCRs within the cell membrane, ultimately eliciting distinct cellular responses. Traditionally, T cells and B cells have been studied independently, with researchers working in parallel to decipher the mechanisms of activation. While these investigations have unveiled many overlaps in how these cell types sense and respond to antigens, notable differences exist. To fully grasp their biology and harness it for therapeutic purposes, these distinctions must be considered. This review compares and contrasts the TCR and BCR, placing emphasis on the role of mechanical force in regulating the activity of both receptors to shape cellular and humoral adaptive immune responses.
  • Journal article
    Connolly JB, Burt A, Christophides G, Diabate A, Habtewold T, Hancock PA, James AA, Kayondo JK, Lwetoijera DW, Manjurano A, McKemey AR, Santos MR, Windbichler N, Randazzo Fet al., 2024,

    Publisher Correction: Considerations for first field trials of low-threshold gene drive for malaria vector control

    , Malaria Journal, Vol: 23, ISSN: 1475-2875

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