Biology subjects

Davies, J.

Publications and source records attributed to Davies, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

LIMD1 Loss as an Early Driver of PD-L1 Upregulation and Immune Evasion in Lung Cancer

LIMD1 is a tumour suppressor gene frequently lost in non-small cell lung cancer (NSCLC), but its role in cancer-immune cell interactions remains unexplored. Here, we demonstrate that LIMD1 loss results in upregulation of the key immune checkpoint protein PD-L1. Using multi-region sequencing from the TRACERx dataset, we identify that LIMD1 loss is clonal in over 80% of squamous cell carcinoma (LUSC) and 40% of lung adenocarcinoma (LUAD) cases, correlating with increased PD-L1 expression. LIMD1 deficiency results in upregulation of basal and IFN{gamma}-induced PD-L1 expression in NSCLC cells and, consistent with its early loss during oncogenesis, in primary human small airway epithelial cells. Mechanistically, we demonstrate that LIMD1 interacts with the E3 ubiquitin ligase ARIH1 to mediate efficient PD-L1 ubiquitination and degradation, a process that is significantly impaired in LIMD1-deficient cells, resulting in increased PD-L1 stability. As a consequence, LIMD1-deficient tumour cells suppressed CD8+ T cell activation in vitro, and blockade of PD-L1 reversed this suppression. Clinically, we show that LIMD1 loss is associated with enhanced response to immune checkpoint inhibitors (ICIs) in NSCLC patient cohorts, revealing a novel cancer cell-intrinsic correlation of ICI efficacy. Our results uncover a tumour suppressor-mediated mechanism of PD-L1 expression and pave the way for stratified immunotherapy approaches in LIMD1-/- NSCLC.

cancer biology↗

bioRxiv2025

Corticospinal Excitability in Response to Mediolateral Gait Instability

Unpredictable gait disturbances, particularly in the mediolateral direction, pose a significant challenge to stability and are a common contributor to falls. Although the corticospinal tract is critical for gait and postural control, its response to such instabilities remains unclear. To investigate if corticospinal excitability increases during laterally destabilised gait, single-pulse transcranial magnetic stimulations were delivered over the primary motor cortex of 15 healthy individuals during steady-state and laterally destabilised treadmill gait. Full-body kinematics were recorded using an optoelectronic motion capture system. Stimulations with coil displacement >5 mm from the targeted location were excluded. Corticospinal excitability was quantified for four upper- and three lower-leg muscles by the motor evoked potential (MEP) amplitude and compared between steady-state and destabilised gait. Destabilisation resulted in a wider step width and shorter stride duration with increased variability and greater dynamic instability. Foot placement control was increased at mid-swing, along with greater average foot placement error. No differences in corticospinal excitability were observed in the lower-leg muscles. All upper-leg muscles demonstrated greater absolute MEPs in destabilised relative to steady-state gait. After normalising MEP to the pre-stimulus muscle activity, these periods became less pronounced, however, increases were observed in all but the gastrocnemius muscles. These findings suggest heightened readiness of the corticospinal tract projecting to upper-leg muscles during destabilised gait, which could reflect general stabilising strategies such as decreasing stride time and increasing step width. KEY POINTSO_LIMaintaining stability during bipedal gait requires precise control, especially when confronted with unpredictable mediolateral disturbances, a common contributor to falls. C_LIO_LIWhen walking on a treadmill that was laterally destablised, participants adopted a cautious walking strategy characterised by wider step width, shorter stride duration and increased variability. C_LIO_LICorticospinal excitability to upper-leg muscles was greater in destabilised than steady-state gait, corticospinal excitability to lower-leg muscles remained largely unchanged. C_LIO_LIThe observed increases in corticospinal excitability to upper-leg muscles likely reflect a general stabilisation strategy in response to a laterally destabilised walking surface. C_LIO_LIIncreases in MEP gain (MEP amplitude relative to ongoing muscle activity) suggest that changes in corticospinal excitability may reflect additional roles beyond modulating the ongoing muscle activity. C_LI

animal behavior and cognition↗

bioRxiv2024

Enhancer heterogeneity in acute lymphoblastic leukemia drives differential gene expression between patients

Genetic alterations alone cannot account for the diverse phenotypes of cancer cells. Even cancers with the same driver mutation show significant transcriptional heterogeneity and varied responses to therapy. However, the mechanisms underpinning this heterogeneity remain under-explored. Here, we find that novel enhancer usage is a common feature in acute lymphoblastic leukemia (ALL). In particular, KMT2A::AFF1 ALL, an aggressive leukemia with a poor prognosis and a low mutational burden, exhibits substantial transcriptional heterogeneity between individuals. Using single cell multiome analysis and extensive chromatin profiling, we reveal that much transcriptional heterogeneity in KMT2A::AFF1 ALL is driven by novel enhancer usage. Using high resolution Micro-Capture-C in primary patient samples, we also identify patient-specific enhancer activity at key oncogenes such as MEIS1 and RUNX2, driving high levels of expression of both oncogenes in a patient-specific manner. Overall, our data show that enhancer heterogeneity is highly prevalent in KMT2A::AFF1 ALL and may also be a mechanism that drives transcriptional heterogeneity in cancer more generally. Key PointsO_LILeukemia patients with the same driver mutations often display gene expression differences C_LIO_LIUsing chromatin profiling and high resolution 3C methods we show that enhancer heterogeneity drives gene expression differences C_LI

cancer biology↗

bioRxiv2024

Bacteroides thetaiotaomicron enhances H2S production in Bilophila wadsworthia

Sulfate- and sulfite-reducing bacteria (SRB) are a group of strict anaerobes found within the human gut. Bilophila wadsworthia, a sulfite-reducing bacterium which produces hydrogen sulfide (H2S) from taurine and isethionate respiration is a common member of the healthy commensal human gut microbiota, but has been implicated in several disease states including inflammatory bowel disease and colorectal cancer. Bacteroides thetaiotaomicron, one of the most prominent gut bacteria, has sulfatases which release sulfate, serving as a potential substrate for sulfate-reducing bacteria. Here, we showed that when B. thetaiotaomicron and B. wadsworthia were in co-culture, there was a significant increase in B. thetaiotaomicrons growth and in H2S production by B. wadsworthia. Differential gene expression analysis revealed increased expression of B. wadsworthias dsrMKJOP complex in co-culture, which delivers electrons for sulfite reduction to H2S. This was accompanied by a decreased expression of genes associated with taurine, sulfolactate and thiosulfate respiration, indicating that B. thetaiotaomicron may provide an alternative source of sulfite to B. wadsworthia. We hypothesised adenosine 5-phosphosulfate (APS) to be this intermediate. Indeed, B. wadsworthia was able to grow using APS or sulfite as electron acceptors. Endometabolomic and transcriptomic analyses revealed decreased production of indole by B. thetaiotaomicron in co-culture with B. wadsworthia due to enhanced tryptophan utilisation by B. wadsworthia. The results of this microbe-microbe interaction could have significant pro-inflammatory effects in the human gut environment.

microbiology↗

bioRxiv2024

Heterogeneous responses to embryonic critical period perturbations among different components of the Drosophila larval locomotor circuit

As developing neural circuits become functional, they undergo a phase of heightened plasticity that facilitates network tuning in response to intrinsic and/or extrinsic stimuli. These developmental windows are termed critical periods (CPs), because perturbations during, but not outside, the CP can lead to lasting changes, such as the formation of sub-optimal or unstable networks. How separate, but connected elements, within a network might respond differently to a CP perturbation is not well understood. To study this, we used the locomotor network of the Drosophila larva as a model and heat stress as a CP stimulus that has ecological relevance. When embryos experienced heat stress the subsequent development of their locomotor network is changed, creating larvae with reduced crawling speed and decreased network stability. Developing body wall muscles and central neurons are sensitive to heat stress perturbations during distinct, consecutive phases of embryogenesis. Within the CNS, transient embryonic CP perturbation leads to increased synaptic drive from premotor interneurons to motoneurons, which in turn adopt reduced excitability. In contrast, the peripheral neuromuscular junction maintains normal synaptic transmission, despite significant structural changes. Thus, connected elements respond differentially to a CP perturbation, suggesting a sequence, or hierarchy, of network adjustment during the CP.

neuroscience↗

bioRxiv2024

An atlas of expressed transcripts in the prenatal and postnatal human cortex

Alternative splicing is a post-transcriptional mechanism that increases the diversity of expressed transcripts and plays an important role in regulating gene expression in the developing central nervous system. We used long-read transcriptome sequencing to characterise the structure and abundance of full-length transcripts in the human cortex from donors aged 6 weeks post-conception to 83 years old. We identified thousands of novel transcripts, with dramatic differences in the diversity of expressed transcripts between prenatal and postnatal cortex. A large proportion of these previously uncharacterised transcripts have high coding potential, with corresponding peptides detected in proteomic data. Novel putative coding sequences are highly conserved and overlap de novo mutations in genes linked with neurodevelopmental disorders in individuals with relevant clinical phenotypes. Our findings underscore the potential of novel coding sequences to harbor clinically relevant variants, offering new insights into the genetic architecture of human disease. Our cortical transcript annotations are available as a resource to the research community via an online database.

genomics↗

bioRxiv2023

Leveraging machine learning and citizen science data to describe flowering phenology across South Africa

O_LIPhenology -- the timing of recurring life history events--is strongly linked to climate. Shifts in phenology have important implications for trophic interactions, ecosystem functioning and community ecology. However, data on plant phenology can be time consuming to collect and current records are biased across space and taxonomy. C_LIO_LIHere, we explore the performance of Convolutional Neural Networks (CNN) for classifying flowering phenology on a very large and taxonomically diverse dataset of citizen science images. We analyse >1.8 million iNaturalist records for plants listed in the National Botanical Gardens within South Africa, a country famed for its floristic diversity ([~]21,000 species) but poorly represented in phenological databases. C_LIO_LIWe were able to correctly classify images with >90% accuracy. Using metadata associated with each image, we then reconstructed the timing of peak flower production and length of the flowering season for the 6,986 species with >5 iNaturalist records. C_LIO_LIOur analysis illustrates how machine learning tools can leverage the vast wealth of citizen science biodiversity data to describe large-scale phenological dynamics. We suggest such approaches may be particularly valuable where data on plant phenology is currently lacking. C_LI

ecology↗

bioRxiv2023

Airway epithelial cells as a novel intracellular host reservoir for Cryptococcus spores

Human fungal pathogens, including Cryptococcus neoformans, cause 1.5 million annual deaths. Cryptococcus causes disease when it disseminates out of the lung and into the brain which can occur years after initial exposure (latency) via mechanisms that remain unknown. Spores of Cryptococcus display distinct surface epitopes, host-interactions, and disease kinetics to the vegetatively growing yeast morphotype, yet they remain understudied likely contributing to our lack of understanding of pathogenesis. One of the first barriers spores encounter are non-professional phagocytic Airway Epithelial Cells (AECs). Here, we demonstrated that Cryptococcus spores preferentially invade AECs both in vitro and in vivo. Once inside spores can germinate, subsequently replicate, persist and/or escape. This ability to enter AECs correlates with a preferential ability of spore to cross AEC barriers. Together our work indicates that AECs can be invaded by Cryptococcus spores and may serve as a previously ignored intracellular host niche, providing alternative hypothesis for both Cryptococcus dissemination and latency.

microbiology↗

bioRxiv2023

Elevation-dependent patterns of snow-gum dieback are moderated by trait differences between montane and subalpine forests.

Subalpine forests worldwide face the synergistic threats of global warming and increased biotic attack, and the collapse or transition of subalpine forests is predicted in south-eastern Australia under future climates. The recent widespread dieback of subalpine snow gum forests due to increased activity of a native wood-boring longicorn beetle suggests this process may already be underway. We investigated how variation in tree tissue traits and environmental conditions correlated with elevation-dependent spatial patterns of forest mortality. We hypothesised that increased vulnerability of subalpine snow gums to wood-borer-mediated dieback at intermediate elevations was associated with poorly-resolved differences in traits between montane (Eucalyptus pauciflora subsp. pauciflora) and subalpine (E. pauciflora subsp. niphophila) snow-gum subspecies. We first sought to characterise variation and elevation-dependent transitions in 20 structural and drought-related functional traits among 120 healthy trees distributed along a 1000m elevation transect which spanned the subspecies transition zone. Secondly, we surveyed 774 trees across 53 sites between 1280-1980m asl. to explore associations between borer-damage severity, elevation, subspecies, and a subset of traits that differed between subspecies. These snow-gum subspecies exhibited mean differences and/or divergent elevation responses in 25% of traits surveyed, indicating contrasting suites of traits between montane and subalpine subspecies. Increased borer-damage severity across the montane-to-subalpine subspecies transition was correlated with lower bark thickness, whereas reduced borer damage at the highest elevations was associated with greater precipitation and lower temperatures. Our results suggest that due to possessing distinct traits associated with increased borer susceptibility, subalpine snow-gum forests will be subject to increased risk of severe borer-mediated forest dieback under warmer and drier future climates. Identifying traits contributing to species distribution limits and biotic-agent vulnerability remains critical for predicting, monitoring, and possibly mitigating forest and vegetation declines under future climates.

ecology↗

bioRxiv2023

Neutron capture enhances dose and reduces cancer cell viability in and out of beam during helium and carbon ion therapy.

PurposeNeutron Capture Enhanced Particle Therapy (NCEPT) is a proposed augmentation of charged particle therapy which exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with two different targeted neutron capture agents (NCAs). Materials and MethodsHuman glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs, [10B]-BPA and [157Gd]-DOTA-TPP. Cells were positioned within a PMMA phantom either laterally adjacent to, or within, a 100x100x60 mm spread out Bragg peak (SOBP). The impact of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in six independent experiments. Neutron fluence within the phantom was characterised by quantifying the neutron activation of gold foil. ResultsCells placed inside the treatment volume reached 10% survival by 2 Gy of C or 2-3 Gy of He in the presence of NCAs compared to 5 Gy of C and 7 Gy of He with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of C or He (to the treatment volume), compared to a no detectable effect on cells without NCA. The mean thermal neutron fluence at the centre of the SOBP was approximately 2.2x109 n/cm2/Gy(RBE) for the carbon beam and 5.8x109 n/cm2/Gy(RBE) for the helium beam and gradually decreased in all directions. ConclusionsThe addition of NCAs to cancer cells during C and He beam irradiation has a measurable impact on cell survival and growth in-vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumours, by targeting this dose to micro-infiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumour tissue within the treatment volume, with a reduction in radiation doses to off target tissue.

biophysics↗

bioRxiv2023

Convergent evolution of monocyte differentiation in adult skin permits repair of the Langerhans cell network

Langerhans cells (LCs) maintain tissue and immunological homeostasis at the epidermal barrier site. They are unique among phagocytes in functioning both as embryo-derived, tissue-resident macrophages that influence skin innervation and repair, and as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DCs). Here we report the mechanisms that determine this dual identity. Using ablation of embryo-derived LCs in murine adult skin and tracked differentiation of incoming monocyte-derived replacements, we reveal intrinsic intra-epidermal heterogeneity. We demonstrate that monocyte-dendritic cell progenitor (MDP)-derived monocytes are selected for survival in the skin environment. Within the epidermis, the hair follicle niche subsequently provides an initial site of LC commitment, likely via Notch signaling, prior to metabolic adaptation and survival of differentiated monocyte-derived LCs. In human skin, we show that embryo-derived (e)LCs in newborns retain transcriptional evidence of their macrophage origin, but this is superseded by distinct DC-like immune modules after post-natal expansion of eLCs. Thus, intrinsic and extrinsic adaptations to adult skin niches replicate conditioning of eLC at birth, permitting repair of the unique LC network.

immunology↗

bioRxiv2023

Ancient genomic linkage couples metabolism with erythroid development

Generation of mature cells from progenitors requires tight coupling of differentiation and metabolism. During erythropoiesis, erythroblasts are required to massively upregulate globin synthesis then clear extraneous material and enucleate to produce erythrocytes1-3. Nprl3 has remained in synteny with the -globin genes for >500 million years4, and harbours the majority of the -globin enhancers5. Nprl3 is a highly conserved inhibitor of mTORC1, which controls cellular metabolism. However, whether Nprl3 itself serves an erythroid role is unknown. Here, we show that Nprl3 is a key regulator of erythroid metabolism. Using Nprl3-deficient fetal liver and adult competitive bone marrow - fetal liver chimeras, we show that NprI3 is required for sufficient erythropoiesis. Loss of Nprl3 elevates mTORC1 signalling, suppresses autophagy and disrupts erythroblast glycolysis and redox control. Human CD34+ progenitors lacking NPRL3 produce fewer enucleated cells and demonstrate dysregulated mTORC1 signalling in response to nutrient availability and erythropoietin. Finally, we show that the -globin enhancers upregulate NprI3 expression, and that this activity is necessary for optimal erythropoiesis. Therefore, the anciently conserved linkage of NprI3, -globin and their associated enhancers has enabled coupling of metabolic and developmental control in erythroid cells. This may enable erythropoiesis to adapt to fluctuating nutritional and environmental conditions.

cell biology↗

bioRxiv2023

Machine learning to classify mutational hotspots from molecular dynamics simulations

Benzo[a]pyrene, a notorious DNA-damaging carcinogen, belongs to the family of polycyclic aromatic hydrocarbons commonly found in tobacco smoke. Surprisingly, nucleotide excision repair (NER) machinery exhibits inefficiency in recognising specific bulky DNA adducts including Benzo[a]pyrene Diol-Epoxide (BPDE), a Benzo[a]pyrene metabolite. While sequence context is emerging as the leading factor linking the inadequate NER response to BPDE adducts, the precise structural attributes governing these disparities remain inadequately understood. We therefore combined the domains of molecular dynamics and machine learning to conduct a comprehensive assessment of helical distortion caused by BPDE-Guanine adducts in multiple gene contexts. Specifically, we implemented a dual approach involving a random forest classification-based analysis and subsequent feature selection to identify precise topological features that may distinguish adduct sites of variable repair capacity. Our models were trained using helical data extracted from duplexes representing both BPDE hotspot and non-hotspot sites within the TP53 gene, then applied to sites within TP53, cII, and lacZ genes. We show our optimised model consistently achieved exceptional performance, with accuracy, precision, and f1 scores exceeding 91%. Our feature selection approach uncovered that discernible variance in regional base pair rotation played a pivotal role in informing the decisions of our model. Notably, these disparities were highly conserved among TP53 and lacZ duplexes and appeared to be influenced by the regional GC content. As such, our findings suggest that there are indeed conserved topological features distinguishing hotspots and non-hotpot sites, highlighting regional GC content as a potential biomarker for mutation. Author SummaryAlthough much is known about DNA repair processes, we are still lacking some fundamental understanding relating to DNA sequence and mutation rates, specifically why some sequences mutate at a higher rate or are repaired less than others. We believe that by using a combination of Molecular Simulation and Machine Learning (ML) we can measure which structural features are present in sequences which mutate at higher rates in cancer gene and lab-based test assays frequently used to investigate toxicology. Here we have run Molecular Dynamics on five sets of DNA sequences with and without a carcinogen found in cigarette smoke to allow us to study the mutation event that would need to be repaired. We have measured their helical and base stacking properties. We have used ML to successfully differentiate between low and high mutating sequences using this model allowing us to begin to elucidate the structural features these groups have in common. We believe this method could have wide reaching uses, it could be applied to any gene context and mutation event and indeed the knowledge of the structural features which are best repaired gives us insight into the biophysics of DNA repair adding knowledge to the drug design pipeline.

biochemistry↗

bioRxiv2023

Structural and biophysical analysis of a Haemophilus influenzae tripartite ATP-independent periplasmic (TRAP) transporter

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-EM structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 [A] resolution (extending to 2.2 [A] at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 [A] resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (KD) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the elevator-with-an-operator mechanism of TRAP transporters.

biochemistry↗

bioRxiv2023

Phenotypic screen-based discovery of a small molecule that can increase adult neurogenesis and improve memory

Stem cells and neurogenesis persist in the postnatal and adult brain. Adult brain stem cells can be neuroprotective in disease and augment hippocampal-dependent cognitive function and thus are an important therapeutic target. Although many molecules have been discovered that regulate neurogenesis, few studies have attempted to amplify the process pharmacologically as a therapeutic goal. To address this gap, we used murine neurosphere cultures from the two major stem cell niches: the subventricular zone (SVZ) and the subgranular zone (SGZ). We screened compounds sharing pharmacophores with known inducers of neurogenesis and found several dozen proneurogenic compounds in an in vitro phenotypic screen. One, OXS-N1 was stable, and had acceptable absorption, distribution, metabolism, and excretion profiles in animal studies. OXS-N1 could increase neurogenesis in the SVZ and SGZ in WT mice after both intraperitoneal and oral administration. The number of newborn neurons (BrdU+/NeuN+) was increased; however, the number of activated stem cells (BrdU+/GFAP+) was not, suggesting an effect on neurogenesis independent of stem cell activation. This was supported by OXS-N1 increasing neurosphere differentiation but not proliferation. OXS-N1 also increased neurogenesis and improved performance in a Y maze cognitive task in PDGF-APPSw,Ind mice, a model of Alzheimers disease. RNAseq of SVZ and SGZ neurospheres in turn showed that genes associated with synaptic function were significantly increased by OXS-N1. Our study demonstrates the utility of phenotypic screening for the identification of molecules that increase neurogenesis and might be of therapeutic relevance.

neuroscience↗

bioRxiv2023

Social influences on delayed gratification in New Caledonian crows and Eurasian jays

Self-control underlies goal-directed behaviour in humans and other animals. Delayed gratification - a measure of self-control - requires the ability to tolerate a delay and/or invest more effort to obtain a reward of higher value over one of lower value, such as food or mates. Social context, in particular, the presence of competitors, may influence delayed gratification. We adapted the rotating-tray paradigm, where subjects need to forgo an immediate, lower-quality (i.e. less preferred) reward for a delayed, higher-quality (i.e. more preferred) one, to test social influences on delayed gratification in two corvid species: New Caledonian crows and Eurasian jays. We compared choices for immediate vs. delayed rewards while alone, in the presence of a competitive conspecific and in the presence of a non-competitive conspecific. We found that species differed: jays were more likely to select the immediate, less preferred reward than the crows. We also found that jays were more likely to select the immediate, less preferred reward when a competitor or non-competitor was present than when alone, or when a competitor was present compared to a non- competitor, while the crows selected the delayed, highly preferred reward irrespective of social presence. We discuss our findings in relation to species differences in socio-ecological factors (adult sociality and food caching) and wider implications of social influences on self-control.

animal behavior and cognition↗

bioRxiv2023

Barley cultivars shape the abundance, phenotype, genotype and gene expression of their associated microbiota by differential root exudate secretion

Plant associated microbes play vital roles in promoting plant growth and health, with plants secreting root exudates into the rhizosphere to attract beneficial microbes. Exudate composition defines the nature of microbial recruitment, with different plant species attracting distinct microbiota to enable optimal adaptation to the soil environment. To more closely examine the relationship between plant genotype and microbial recruitment, we analysed the rhizosphere microbiomes of landrace (Chevallier) and modern (NFC Tipple) barley cultivars. Distinct differences were observed between the plant-associated microbiomes of the two cultivars, with the plant-growth promoting rhizobacterial genus Pseudomonas substantially more abundant in the Tipple rhizosphere. Striking differences were also observed between the phenotypes of recruited Pseudomonas populations, alongside distinct genotypic clustering by cultivar. Cultivar-driven Pseudomonas selection was driven by root exudate composition, with the greater abundance of hexose sugars secreted from Tipple roots attracting microbes better adapted to growth on these metabolites, and vice versa. Cultivar-driven selection also operates at the molecular level, with both gene expression and the abundance of ecologically relevant loci differing between Tipple and Chevallier Pseudomonas isolates. Finally, cultivar-driven selection is important for plant health, with both cultivars showing a distinct preference for microbes selected by their genetic siblings in rhizosphere transplantation assays.

microbiology↗

bioRxiv2023

Community phylogenetic structure shapes pathogen outbreak potential in an epidemiological multi-host model

Biodiversity loss and anthropogenic modifications to species communities are impacting the frequency and magnitude of disease emergence events. These changes may be related through mechanisms in which biodiversity either increases (amplifies) or decreases (dilutes) disease prevalence. Biodiversity effects can be direct, when contacts among competent hosts are substituted by contacts with sink hosts, or indirect through regulation of host abundances. Whether a disease is diluted or amplified depends on the competence of the host species in the community. Here, we introduce a multi-host compartmental disease model in which we assume that host competence is determined by evolutionary relatedness. By simulating communities of varying phylogenetic structure, and estimating community disease outbreak potential (R0), we show how differences in host phylogenetic relatedness can switch host communities from diluting to amplifying a disease, even when species richness is unchanged. We additionally show that phylogenetic dilution can occur simultaneously with amplification through species richness, highlighting the multidimensionality of the disease-diversity relationship. We illustrate our model using empirical data describing the relationship between phylogenetic distances separating hosts and their likelihood of disease sharing. Our study demonstrates how a phylogenetic dilution effect can emerge when we allow transmission to depend on host evolutionary histories.

ecology↗