Biology subjects

Turnbull, C.

Publications and source records attributed to Turnbull, C..

12 recordsLinked to original sources

bioRxiv2026

Significant increase in root exudation of 2'-deoxymugineic acid (DMA) as a response to zinc deficiency in rice

1O_LIZinc (Zn) deficiency limits rice productivity and poses a risk to human health, particularly in populations reliant on rice-based diets. Although rice germplasm exhibits wide variation in Zn-deficiency tolerance, the underlying physiological mechanisms remain poorly resolved. Evidence across the literature for Zn-deficiency-induced secretion of 2'-deoxymugineic acid (DMA) is inconsistent. This study clarifies the role of DMA secretion as a Zn-deficiency stress response. C_LIO_LIWe developed and validated a sensitive LC-ESI-Q-TOF-MS method for selective detection of DMA in rice root exudates. Five rice genotypes with contrasting Zn-deficiency tolerance were grown hydroponically and DMA secretion measured. C_LIO_LIZn-deficiency increased DMA exudation across all genotypes, with sensitive genotypes also showing higher secretion compared with control, supporting DMAs role as a general response to Zn stress rather than being restricted to efficient genotypes. C_LIO_LIFold-change responses exceeded previous studies, likely due to more severe stress exposure. Our results confirm that DMA secretion is induced under Zn-deficiency in rice as part of the micronutrient stress response. However, the lack of increased Zn uptake indicates that additional tolerance mechanisms are involved. These findings reconcile inconsistencies in the literature and position DMA secretion as an important, but not exclusive, component of Zn-deficiency adaptation in rice. C_LI

plant biology↗

bioRxiv2025

A novel chitinase-like family of candidate effectors unique to aphids

Molecular interactions between aphids and plants include delivery of salivary effector proteins into host cells, acting as virulence factors to suppress host immunity, or as avirulence functions triggering immune activation. However, understanding of virulence and avirulence mechanisms in aphid-plant systems is currently limited. Here, we report discovery of an effector candidate family that is unique to aphids. Using functional genomics data on divergent pea aphid (Acyrthosiphon pisum) genotypes and their F1 progeny, we filtered for differentially expressed saliva proteins that co-segregated with virulence or avirulence phenotypes. LOC100575698 (ACPISUM_029930), annotated as an uncharacterized protein, was the sole candidate effector for which RNA-Seq and saliva proteomics data showed significantly different expression both between avirulent and virulent parents and between their segregating F1 progeny, with this gene upregulated in avirulent genotypes. BLASTP searches revealed multiple divergent homologs only in genomes of the Aphidomorpha infra-order, suggesting a hitherto undefined ancient aphid-specific gene family. AlphaFold models indicate strong structural similarities but weak sequence homology to chitinases. Because the aphid-specific clade all lack canonical DxxDxDxE motifs for catalytic activity, we designate the proteins as a novel CHitinase-Like (CHL) family. Association of ACPISUM_029930 (ApCHL1) with avirulence was further supported by co-segregating SNPs and a genotype-specific alternatively spliced isoform. We hypothesise that CHL proteins may function similarly to phylogenetically unrelated chitin-binding fungal effectors that sequester chitin, also present in aphid stylets, potentially preventing defence activation through plant chitin receptors and/or blocking chitin degradation by host-secreted chitinases.

molecular biology↗

bioRxiv2025

Phylogenetics, evolution and biogeography of four Digitaria food crop lineages across West Africa, India, and Europe

Background and AimsMillet crops in the grass genus Digitaria include white and black fonio (D. exilis and D. iburua), raishan (D. compacta) and Polish millet (D. sanguinalis), cultivated across West Africa, India, and Europe. Fonio and raishan crops are important to supporting food security and subsistence agricultural systems in rural communities, while D. sanguinalis is no longer cultivated. These crops are resilient to challenging climates. We aim to produce an integrated study of these crops: a phylogeny of the Digitaria genus including all four food species, to identify key crop wild relatives (CWRs); time-calibrated biogeographic analysis, to investigate the history and evolution of Digitaria; and morphological study to assess the transition between wild and domesticated species. MethodsWe use the Angiosperm 353 target-enrichment sequencing approach to produce maximum likelihood and coalescent model nuclear phylogenies for 46 Digitaria species, including ploidy estimations, and bayesian methods to propose an evolutionary and biogeographic history for the genus. Morphology of wild and cultivated species is investigated for spikelets and growth habits using microscopy and SEM imaging techniques. Key ResultsFour distinct lineages are proposed for the evolution of Digitaria crops, and close CWRs D. fuscescens, D. atrofusca, D. setigera and D. radicosa, and D. ciliaris are identified. South and eastern Africa is proposed as the origin of early Digitaria divergence, with crop lineages diverging from wild relatives around 2-6mya. Incomplete domestication traits are observed, including the loss of trichomes, but no significant difference in spikelet or abscission zone morphology. ConclusionsDigitaria crops have important climate-resilient traits and hold strong potential for stabilising vulnerable food systems against the challenges of future climate change. The knowledge produced in this study about CWRs will be useful in improving crop traits through targeted breeding and indigenous crop conservation programmes.

genetics↗

bioRxiv2024

Multi-omics approaches define novel aphid effector candidates associated with virulence and avirulence phenotypes

BackgroundCompatibility between plant parasites and their hosts is genetically determined by both interacting organisms. For example, plants may carry resistance (R) genes or deploy chemical defences. Aphid saliva contains many proteins that are secreted into host tissues. Subsets of these proteins are predicted to act as effectors, either subverting or triggering host immunity. However, associating particular effectors with virulence or avirulence outcomes presents challenges due to the combinatorial complexity. Here we use defined aphid and host genetics to test for co-segregation of expressed aphid transcripts and proteins with virulent or avirulent phenotypes. ResultsWe compared virulent and avirulent pea aphid parental genotypes, and their bulk segregant F1 progeny on Medicago truncatula genotypes carrying or lacking the RAP1 resistance quantitative trait locus. Differential gene expression analysis of whole body and head samples, in combination with proteomics of saliva and salivary glands, enabled us to pinpoint proteins associated with virulence/avirulence phenotypes. There was relatively little impact of host genotype, whereas large numbers of transcripts and proteins were differentially expressed between parental aphids, likely a reflection of their classification as divergent biotypes within the pea aphid species complex. Many fewer transcripts intersected with the equivalent differential expression patterns in the bulked F1 progeny, providing an effective filter for removing genomic background effects. Overall, there were more upregulated genes detected in the F1 avirulent dataset compared with the virulent one. Some genes were differentially expressed both in the transcriptome and in the proteome datasets, with aminopeptidase N proteins being the most frequent differentially expressed family. In addition, a substantial proportion (27%) of salivary proteins lack annotations, suggesting that many novel functions remain to be discovered. ConclusionsEspecially when combined with tightly controlled genetics of both insect and host, multi-omics approaches are powerful tools for revealing and filtering candidate lists down to plausible genes for further functional analysis as putative aphid effectors.

genomics↗

bioRxiv2024

Induction and characterisation of Abeta and tau pathology in AppNL-F/NL-F mice following inoculation with Alzheimer's disease brain homogenate

Alzheimers disease (AD) is defined by the accumulation of neurofibrillary tangles containing hyperphosphorylated Tau and plaques containing Amyloid-{beta} (A{beta}). The aggregation of these two proteins is considered central to the disease. The lack of animal models that can recapitulate A{beta} and tau pathologies without overexpressing these proteins has hindered AD research. Accelerating pathology by inoculating A{beta} and tau seeds has helped to understand their prion-like propagation in the brain. Previous studies failed to characterise both A{beta} and tau pathologies in vivo upon inoculating AD brain homogenates. Here we present a longitudinal and systematic study; we inoculated the AppNL-F/NL-F knockin mice, which express humanised A{beta} and murine wild-type tau, with extracts from diseased human brains to analyse the contribution of A{beta} and tau assemblies to AD pathogenesis. We found that mice inoculated with AD brain extracts evinced early and prominent amyloid deposition, while those injected with control brain extracts or vehicle did not. Parenchymal and vascular amyloid accumulated in the same brain regions affected in control-inoculated AppNL-F/NL-F mice. However, the extent of vascular amyloid far exceeded that seen in AppNL-F/NL-Fmice injected with control brain extracts, and parenchymal deposits extended to a previously untargeted brain region - the cerebellum. An end-point titration of an AD brain homogenate in AppNL-F/NL-F mice demonstrated that human A{beta} seeds can be titrated in a prion-like fashion, which is useful for sample comparison, diagnostic and risk studies. Notably, the inoculation of AppNL-F/NL-F mice with AD brain homogenate induced intense tau phosphorylation, and provides more detailed context for the inoculation of AppNL-F/NL-F mice with human samples to study temporal and mechanistic relationships between A{beta} and tau pathology, vascular amyloid deposition and bioactivity of A{beta} seeds.

neuroscience↗

bioRxiv2022

IPT9, a cis-zeatin cytokinin biosynthesis gene, promotes root growth

Cytokinin and auxin are plant hormones that coordinate many aspects of plant development. Their interactions in plant underground growth are well established, occurring at the levels of metabolism, signaling, and transport. Unlike many plant hormone classes, cytokinins are represented by more than one active molecule. Multiple mutant lines, blocking specific parts of cytokinin biosynthetic pathways, have enabled research in plants with deficiencies in specific cytokinin-types. While most of these mutants have confirmed the impeding effect of cytokinin on root growth, the ipt29 double mutant instead surprisingly exhibits reduced primary root length compared to wild type. This mutant is impaired in cis-zeatin (cZ) production, a cytokinin-type that had been considered inactive in the past. Here we have further investigated the intriguing ipt29 root phenotype, opposite to known cytokinin functions, and the (bio)activity of cZ. Our data suggest that despite the ipt29 short-root phenotype, cZ application has a negative impact on primary root growth and can activate a cytokinin response in the stele. Grafting experiments revealed that the root phenotype of ipt29 depends on local signaling which does not relate to directly to cytokinin levels. Notably, ipt29 displayed increased auxin levels in the root tissue. Moreover, analyses of the differential contributions of ipt2 and ipt9 to the ipt29 short-root phenotype demonstrated that, despite its deficiency on cZ levels, ipt2 does not show any root phenotype or auxin homeostasis variation while ipt9 mutants were indistinguishable from ipt29. We conclude that IPT9 functions may go beyond cZ biosynthesis, directly or indirectly, implicating effects on auxin homeostasis and therefore influencing plant growth.

plant biology↗

bioRxiv2021

Different plasticity of bud outgrowth at cauline and rosette nodes in Arabidopsis thaliana

Shoot branching is a complex mechanism in which secondary shoots grow from buds that are initiated from meristems established in leaf axils. The model plant Arabidopsis thaliana has a rosette leaf growth pattern in the vegetative stage. After flowering initiation, the main stem starts to elongate with the top leaf primordia developing into cauline leaves. Meristems in arabidopsis are initiated in the axils of rosette or cauline leaves, giving rise to rosette or cauline buds, respectively. Plasticity in the process of shoot branching is regulated by resource and nutrient availability as well as by plant hormones. However, few studies have attempted to test whether cauline and rosette branching are subject to the same plasticity. Here, we addressed this question by phenotyping cauline and rosette branching in three arabidopsis ecotypes and several arabidopsis mutants with varied shoot architectures. Our results show that there is no negative correlation between cauline and rosette branch numbers in arabidopsis, demonstrating that there is no trade-off between cauline and rosette bud outgrowth. Through investigation of the altered branching pattern of flowering pathway mutants and arabidopsis ecotypes grown in various photoperiods and light regimes, we further elucidated that the number of cauline branches is closely related to flowering time. The number or rosette branches has an enormous plasticity compared with cauline branches and is influenced by genetic background, flowering time, light intensity and temperature. Our data reveal different plasticity in the regulation of branching at rosette and cauline nodes and promote a framework for future branching analyses. One sentence summaryDifferent plasticity of branching at cauline and rosette nodes of arabidopsis is revealed through detailed correlative analyses of branching under varied genetic and environmental contexts.

plant biology↗

bioRxiv2021

Germline loss-of-function variants in the base-excision repair gene MBD4 cause a Mendelian recessive syndrome of adenomatous colorectal polyposis and acute myeloid leukaemia

Inherited defects in base-excision repair (BER) predispose to adenomatous polyposis and colorectal cancer (CRC), yet our understanding of this important DNA repair pathway remains incomplete. By combining detailed clinical, histological and molecular profiling, we reveal biallelic germline loss-of-function (LOF) variants in the BER gene MBD4 to predispose to adenomatous polyposis and -uniquely amongst CRC predisposition syndromes- to myeloid neoplasms. Neoplasms from MBD4-deficient patients almost exclusively accumulate somatic CpG>TpG mutations, resembling mutational signature SBS1. MBD4-deficient adenomas harbour mutations in known CRC driver genes, although AMER1 mutations were more common and KRAS mutations less frequent. We did not find an increased risk for colorectal tumours in individuals with a monoallelic MBD4 LOF variant. We suggest that this condition should be termed MBD4-associated neoplasia syndrome (MANS) and that MBD4 is included in testing for the genetic diagnosis of polyposis and/or early-onset AML.

genetics↗

bioRxiv2019

Germline and somatic genetic variants in the p53 pathway interact to affect cancer risk, progression and drug response

Insights into oncogenesis derived from cancer susceptibility loci could facilitate better cancer management and treatment through precision oncology. However, therapeutic applications have thus far been limited by our current lack of understanding regarding both their interactions with somatic cancer driver mutations and their influence on tumorigenesis. Here, by integrating germline datasets relating to cancer susceptibility with tumour data capturing somatically-acquired genetic variation, we provide evidence that single nucleotide polymorphism (SNPs) and somatic mutations in the p53 tumor suppressor pathway can interact to influence cancer development, progression and treatment response. We go on to provide human genetic evidence of a tumor-promoting role for the pro-survival activities of p53, which supports the development of more effective therapy combinations through their inhibition in cancers retaining wild-type p53. SignificanceWe describe significant interactions between heritable and somatic genetic variants in the p53 pathway that affect cancer susceptibility, progression and treatment response. Our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel therapeutic targets.

cancer biology↗

bioRxiv2019

Cell-surface receptors enable perception of extracellular cytokinins

Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience 1,2. Although cytokinin receptors are substantially localised to the endoplasmic reticulum 3-5, the cellular sites of cytokinin perception continue to be debated 1,6,7. Several cytokinin types display bioactivity 8,9 and recently a cell-specific cytokinin gradient was reported in roots 10. Yet, the importance of spatially heterogeneous cytokinin distribution and the specific cytokinin(s) that account for the different responses remain unclear. Here we show that cytokinin perception by plasma membrane receptors is an effective path for cytokinin response in root cells. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP;11) is closely matched to intracellular cytokinin content, yet a proportion of bioactive cytokinins are detected in the extracellular fluid. Using cytokinins covalently linked to beads that could not pass the plasma membrane, we demonstrate that strong TCSn activation still occurs and that this response is greatly diminished in cytokinin receptor mutants. Although intracellular receptors play significant roles, we argue for a revision of concepts of cytokinin perception to include the spatial dimensions. In particular, selective ligand-receptor affinities, cellular localisation and tissue distribution of bioactive cytokinins, their receptors, transporters and inactivation enzymes appear all to be components of the signalling regulatory mechanisms.

plant biology↗

bioRxiv2019

Genetic predisposition to mosaic Y chromosome loss in blood is associated with genomic instability in other tissues and susceptibility to non-haematological cancers

Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism, yet our knowledge of the causes and consequences of this is limited. Using a newly developed approach, we estimate that 20% of the UK Biobank male population (N=205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes involved in cell-cycle regulation, cancer susceptibility, somatic drivers of tumour growth and cancer therapy targets. Genetic susceptibility to LOY is associated with non-haematological health outcomes in both men and women, supporting the hypothesis that clonal haematopoiesis is a biomarker of genome instability in other tissues. Single-cell RNA sequencing identifies dysregulated autosomal gene expression in leukocytes with LOY, providing insights into how LOY may confer cellular growth advantage. Collectively, these data highlight the utility of studying clonal mosaicism to uncover fundamental mechanisms underlying cancer and other ageing-related diseases.

genetics↗

bioRxiv2017

Nitrate modulates stem cell dynamics by regulating WUSCHEL expression through cytokinins

The shoot apical meristem (SAM) is responsible for the generation of all of the aerial parts of plants1. Given its critical role, dynamical changes in SAM activity should play a central role in the adaptation of plant architecture to the environment2. Using quantitative microscopy, grafting experiments and genetic perturbations, we connect the plant environment to the SAM, by describing the molecular mechanism by which cytokinins signal the level of nutrient availability to the SAM. We show that a systemic signal of cytokinin precursors3 mediates the adaptation of SAM size and organogenesis rate to the availability of mineral nutrients by modulating the expression of WUSCHEL, a key regulator of stem cell homeostasis4. In time-lapse experiments, we further show that this mechanism allows meristems to adapt to rapid changes in nitrate concentration, and thereby modulate their rate of organ production to the availability of mineral nutrients within a few days. Our work sheds new light on the role of the stem cell regulatory network, by showing that it does not only maintain meristem homeostasis but also allows plants to adapt to rapid changes in the environment.

plant biology↗