Biology subjects

Young, A.

Publications and source records attributed to Young, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Moving object generates topographic responses in the majority of entorhinal neurons

Vision is crucial in generating a complex array of responses in rodents during spatial exploration and in humans during memory tasks. These tasks involve other variables too, e.g. multisensory cues in rodents and complex memories in humans. Further, there are major differences between the medial and lateral entorhinal cortical (MEC and LEC) functional cell types. To understand the contribution of purely visual information to entorhinal responses, we presented a simple, moving vertical bar of light to head-fixed mice, without any task or reward. Surprisingly, 66% (2391/3601) of the MEC broad spiking neurons were significantly modulated by the bar position on the screen. Visual tuning in MEC had a pronounced dorsoventral topography --the tuning strength dropped from 79% in the dorsal most quartile to 40% in the ventral most quartile. Unlike major differences in spatial and other codes between MEC and LEC during free foraging experiments, LEC cells showed very similar visual tuning (392/606, 65%), including the dorso-ventral gradient in LEC5. Additionally, the majority of putative interneurons, from MEC as well as LEC, showed similar, widespread visual tuning, unlike spatial tasks. Neurons also encoded the object motion direction (naso-temporal vs. temporo-nasal visual motion) with changes in mean rate, tuning strength and/or tuning location. Such directional nature of visual tuning indicates significant history-dependence or sequence encoding. Consistently, replacing the continuous motion by randomly flashing bar of light abolished bar-tuning in two-thirds of continuous bar-tuned cells and substantially altered tuning in the rest. These results reveal the contribution of purely visual inputs in generating anatomically organized responses in the majority of entorhinal neurons. The prevalence and similarity of visual tuning across all layers of MEC as well as LEC exceeds that of other known functional cell types (like grid cells in MEC or egocentric object tuning/time-cells in LEC) during spatial navigation tasks and could be foundational in understanding entorhinal complexity.

neuroscience↗

bioRxiv2026

SpiraMed: A Stereotactic Helix-based Therapy Delivery system for the Human Brain

Stereotactic needle-based delivery remains the standard for local administration of Advanced Therapy Medicinal Products (ATMPs) to the human brain. ATMP administration typically involves multiple trajectories, presenting cumulative risks and prolonging surgery. Reflux-prone, patchy therapy coverage compromises clinical results. We demonstrate a novel approach, deploying a helical delivery catheter via a single access trajectory per target, referred to as SpiraMed. Helix retraction is synchronised with therapy delivery, enabling comprehensive target coverage in seconds. Helix pitch and diameter can be precisely tailored to patient-specific target volume and vascular anatomy, as part of the preoperative stereotactic surgical planning process. Testing in agarose phantoms, live sheep and cadaveric human brain confirms enhanced therapy delivery volume, delivery speed and target coverage, with reductions in reflux and predicted risk of bleeding complication. SpiraMed represents a new paradigm, promising to help deliver on the transformative potential of cell and gene therapies across the spectrum of human CNS disease.

bioengineering↗

bioRxiv2026

Cholesterol and p53 promote senescence and systemic fibrosis in metabolic dysfunction-associated steatohepatitis

Background & aims: TP53 (p53) coordinates diverse cellular stress response programmes including pro-survival activities, senescence, and cell death. During tissue damage, p53 can shape both the local cellular response to injury, including the fibrotic response, and influence distal organ biology. Fibrosis in the liver is a major driver of hepatocellular carcinoma (HCC) risk within metabolic dysfunction-associated steatohepatitis (MASH). It is also an important determinant of dysfunction in multiple distal tissues including the kidneys, lungs, and heart. Despite significant clinical burden, our understanding of the molecular determinants of fibrotic MASH and its relationship to multiorgan fibrosis remain incomplete. Here, we investigate local and systemic effects of hepatocellular p53 activity and cholesterol during MASH development, with implications for disease prevention. Methods: This study utilised a genetic model of stabilised p53, diet-induced MASH models with varying cholesterol compositions, and an in vitro obesogenic system to investigate p53 activity during liver disease development. Non-invasive imaging and histopathological analyses were employed to monitor p53 activity, MASH, and multiorgan fibrosis in vivo. Complementary approaches, including in vitro human multicomponent liver spheroids, cytokine arrays, and analyses of human MASH transcriptomic and proteomic datasets, were used to examine molecular drivers and patient relevance. Results: Using an inducible mouse model of MDM2 E3 ubiquitin ligase deficiency to stabilise p53, we report that hepatocellular MDM2 E3 loss results in progressive fibrotic damage, robust hepatocellular expression of the p53 target gene CDKN1A/p21 (p21),and induces p21 and fibrosis in the kidneys of male mice in a sex-specific manner. In diet-induced MASH, we observe cholesterol and p53-dependent development of liver fibrosis, high expression of hepatocellular p21, and induction of p21 and fibrosis in the kidneys of male mice-reminiscent of features observed in MDM2 E3-deficient mice. We also observe fibrosis in the lungs and heart of male MASH mice. Both a cholesterol-free obesogenic diet and liver-specific loss of p53 mitigate hepatic fibrosis and systemic induction of p21 and fibrosis. Mechanistically, p53 induces hepatic expression of senescence-associated secretory phenotype (SASP) factors, including GDF15, in vivo. A human multicomponent LiverACE spheroid model showed a concordant trend towards increased GDF15 protein abundance under steatotic stress, while in humans, elevated circulating GDF15 levels in advanced MASH correlate with increased TNFRSF1A and EPHA2, circulating markers linked to kidney injury. Conclusions: Our work identifies undue p53 activity within the liver as a driver of multiorgan fibrosis in a sex-specific manner, affecting male but not female mice. We implicate cholesterol in promoting this pro-fibrotic environment in vivo and highlight circulating factors that could identify at-risk patients for multiorgan fibrosis in MASH.

cancer biology↗

bioRxiv2026

Resting-state and task-evoked phase-amplitude coupling between cardiac and neural rhythms is sensitive to anxiety severity

Background. High-frequency heart-rate variability (HF-HRV) is a downstream marker of cortico-autonomic regulation linked to executive function. A recent proposal suggests it indexes regulatory processes because it is both a product of and contributor to neural organization within the prefrontal cortex. The oscillatory phase of HF-HRV has been reported to modulate fronto-central EEG amplitude at rest, and this coupling is attenuated in individuals with schizophrenia relative to healthy controls. We evaluated this brain-body correspondence in relation to anxiety symptomatology, which is likewise associated with autonomic dysregulation. Methods. Concurrent EEG and electrocardiography (ECG) were recorded in 22 nonclinical adults at rest and during a mental arithmetic task. Participants rated anxiety severity using the Generalized Anxiety Disorder 7-item scale (GAD-7). We evaluated between-person associations between anxiety severity and HF-HRV-EEG coupling, as well as within-person differences in coupling between rest and mental arithmetic. Results. Anxiety symptomatology was associated with decreased resting-state phase-amplitude coupling between HF-HRV phase and fronto-central theta amplitude, independent of EEG and HRV covariates. Relative to rest, HF-HRV-theta coupling increased during a cognitive task, independent of condition-related changes in EEG, HR, or respiration. Anxiety severity moderated the task-evoked changes in heart-brain coupling such that more anxious individuals exhibited larger condition-related differences. Simple-slope analyses indicated the effect of anxiety on coupling at rest was absent when engaged in a task. Conclusions. HF-HRV-theta phase-amplitude coupling captured anxiety-related and state-dependent variance not evident in conventional cardiac or neural indices. This coupling may index a state-sensitive component of cortico-autonomic regulation, although its putative functional role requires direct testing.

neuroscience↗

bioRxiv2026

Inflammatory arthritis disrupts ocular immune privilege by compromising blood-retinal barrier integrity and promoting uveitogenic T cell recruitment

Inflammatory arthritis and uveitis frequently co-exist, yet the mechanisms linking joint and ocular inflammation remain ill-defined. Here, we investigated how inflammatory arthritis influences ocular immune homeostasis using murine models of antigen-induced arthritis and collagen-induced arthritis. Arthritis promoted the accumulation of T cells, myeloid cells, and neutrophils within the vitreoretinal compartment, without progression to overt clinical uveitis. Ocular leukocyte recruitment was dynamically coupled to arthritis activity, resolving with remission of joint inflammation and recurring during arthritic flares. The magnitude of ocular immune perturbation correlated with arthritis severity, being enhanced in IL-27R-deficient mice and markedly reduced in IL-6R-deficient mice. Mechanistically, arthritis increased blood-retinal barrier permeability, demonstrating that systemic inflammation perturbs ocular immune privilege even in the absence of apparent ocular disease. While arthritis alone was insufficient to induce uveitis, it established a permissive ocular microenvironment that selectively enhanced the recruitment of adoptively transferred uveitogenic CD4+ T cells. These findings identify inflammatory arthritis as a systemic driver of subclinical ocular immune dysregulation and reveal a mechanism by which inflammation at a distant site may promote vulnerability to ocular autoimmunity. These data provide a framework for understanding immune dysregulation at the joint-eye axis and highlight cytokine pathways that may be targeted to preserve ocular immune homeostasis.

immunology↗

bioRxiv2026

Phenotype-environment matching in ground-nesting birds across and within large-scale biomes

Many animals have camouflage appearances that correspond to the habitat where they live, termed phenotype-environment matching. However, this has generally been tested in only a limited number of systems and natural settings, and often not to the relevant vision of key receivers (predators) across different spatial scales. Here, we measured the plumage attributes and putative camouflage used by ground-nesting bird species specialist to particular biomes, specifically tropical rainforest, taiga forest, dry forest, grassland, desert, and tundra from museum specimens. Digital photography and image analysis were used to quantify colour patterns to models of predator vision to understand how different colour patterns may correspond with biome type. With this information, we next created bird models that were photographed in situ in the Valdivian temperate rainforest and Patagonian grassland biomes of Chile to quantify the extent to which plumage coloration and pattern traits provide effective camouflage at different spatial scales. In general, we find that specialist ground-nesting birds express a phenotype that better matches the substrate composition and vegetation structure across large spatial scales of their own biome. This study reveals how animal camouflage works across biomes, relative to the visual system of raptor predators, and at the appropriate distance at which detection may occur.

ecology↗

bioRxiv2026

Comprehensive Lineage Tracing Maps the Landscape of Cell Fate Decisions in Mouse Embryogenesis

A comprehensive cell fate map of mammalian embryogenesis has remained out of reach due to the scale, cellular diversity, and non-deterministic nature of development in utero. Here, we use PEtracer to continuously install heritable genetic marks as cells divide, reconstructing lineage trees that resolve [~]75% of cell divisions across >1.5 million cells from 16 mouse embryos collected at half-day intervals from E7.5-E10.0. We pair these trees with deep transcriptional profiling to chart the landscape of cell fate decisions during gastrulation and early organogenesis. Using these data, we quantify cell fate biases, restriction timing, progenitor pool sizes, and lineage relationships across the embryo, revealing strikingly reproducible lineage architecture across replicate embryos despite the regulative flexibility of mammalian development. We further show how lineage, spatial position, and signaling jointly determine fate outcomes and timing, with their relative influence varying by tissue. This dataset provides a quantitative framework for understanding cell fate specification and a lineage-resolved reference for generating and contextualizing developmental hypotheses at organismal scale.

developmental biology↗

bioRxiv2026

Focal adhesion kinase promotes metastasis in BRAF-mutant melanoma

Despite the availability of several FDA-approved therapies, metastatic melanoma remains a significant clinical challenge, particularly for patients with brain metastases, which frequently represent the site of treatment failure and a major cause of melanoma-related mortality. Melanoma exhibits a strong propensity to metastasize to the brain, yet the molecular mechanisms driving this lethal progression remain incompletely understood, limiting the development of effective treatment options. Building on our prior discovery that focal adhesion kinase (FAK) is a key mediator of AKT1-driven brain metastasis, we sought to validate the role of FAK in melanoma progression and metastatic dissemination. Using complementary autochthonous and syngeneic mouse models of BRAF-mutant melanoma, we evaluated the impact of FAK expression on overall survival, primary tumor growth, and metastasis. Through the generation of targeted FAK mutants, we distinguished kinase-dependent from kinase-independent functions and demonstrate that FAK promotes melanoma metastasis in a kinase-dependent manner. Furthermore, we establish that FAK functions downstream of PTEN to drive metastatic progression. Collectively, these findings support the therapeutic potential of FAK inhibition, either alone or in combination with existing treatments, to more effectively combat metastatic melanoma and inform the development of emerging FAK-targeted therapies.

cancer biology↗

bioRxiv2025

OCA-B/Pou2af1 Expression in Mouse T Cells Promotes PD-1 Blockade-Induced Autoimmunity but is Dispensable for Anti-Tumor Immunity

The transcription coregulator OCA-B promotes CD4+ T cell memory recall responses and autoimmunity. OCA-B T cell deletion prevents spontaneous type-1 diabetes (T1D) onset in non-obese diabetic (NOD) mice and blunts T1D in a subset of more aggressive models. However, the role of OCA-B in diabetes induced by treatment with immune checkpoint inhibitors (ICIs), and the role of OCA-B in the control of tumors with and without ICI treatment, has not been studied. Here we show that islet and pancreatic lymph node T cells from T1D individuals express measurable POU2AF1 mRNA. Deletion of OCA-B in T cells fully insulates 8-week-old non-obese diabetic (NOD) mice against ICI-induced diabetes and partially protects 12-week-old mice. Salivary and lacrimal gland infiltration and inflammation were also reduced. Protection was associated with a block in the differentiation of progenitor exhausted CD8+ T cells (TPEX) into terminally exhausted CD8+ T cells (TEX). We show that OCA-B T cell loss preserves anti-tumor immune responses following PD-1 blockade in different tumors and mouse strains. These findings point to a potential therapeutic window in which pharmaceuticals targeting OCA-B could be used to block the emergence of both spontaneous and ICI-induced autoimmunity while sparing anti-tumor immunity. We develop first-in-class small molecule inhibitors of Oct1/OCA-B transcription complexes and show that administration into NOD mice also blocks diabetes emergence following PD-1 blockade. These results identify OCA-B as a promising therapeutic target for the prevention of autoimmunity and immune-related adverse events (irAEs).

immunology↗

bioRxiv2025

Sexual dimorphism in sensorimotor transformation of optic flow

Motion vision underpins a wide range of adaptive behaviours essential for individual and species survival. In hoverflies, some visual behaviours are sexually dimorphic, including for example male high-speed pursuit of conspecifics, matched by improved optics, and faster photoreceptors. Other visual behaviours are sexually monomorphic, with for example similar foraging flight speeds in male and female hoverflies. However, whether the descending neurons responsible for sensorimotor transformation of optic flow are sexually dimorphic is unknown. To address this, we combined morphological analysis with electrophysiology of optic flow sensitive descending neurons and compared neural responses to the behavioural output in tethered hoverflies. We found that while optomotor flight behaviour is largely sexually monomorphic, the underlying neural responses are sexually dimorphic, especially at higher optic flow velocities. Additionally, behavioural responses were noticeably slower than neural responses. Together, our findings uncover a nuanced, sex- and stimulus- dependant sensorimotor transformation, shaped by both neural architecture and behavioural demands.

neuroscience↗

bioRxiv2025

JARID2 Inhibition Reprograms Human Hematopoietic Progenitor Cells To Enhance Bone Marrow Transplantation

Hematopoietic stem cell transplantation is a common treatment for many blood disorders and can be a life-saving therapy for patients with leukemias, lymphomas and multiple myeloma. Umbilical cord blood (UCB) serves as a valuable source of hematopoietic stem and progenitor cells (HSPCs) for transplantation, particularly for patients lacking a matched donor. However, the limited number of repopulating cells in UCB units restricts its clinical utility. Our prior studies showed that genetic deletion of the polycomb repressive complex 2 (PRC2) co-factor Jarid2 in mouse multipotent progenitors (MPPs) conveyed ectopic self-renewal capacity. Here, we hypothesized that the function of human HSPCs could be enhanced through JARID2 inhibition. In this study, we demonstrate that both constitutive and transient knockdown of JARID2 increases the number and enhances the functionality of human HSPCs both in vitro and in vivo. This phenotype was distinct from inhibition of EZH2 in UCB cells, suggesting the mechanism was independent of PRC2 co-factor activity of JARID2. Mechanistically, JARID2 knockdown promotes a quiescent, long-term self-renewal gene expression program governed by upregulating STAT1 and characterized by an MHC class II immunophenotype. Analogous to mice, these mechanisms conferred HSC-like potential to human MPPs in vivo. Taken together, these findings highlight JARID2 inhibition as a novel and reversible approach to expand functional UCB-derived HSPCs ex vivo, potentially improving access to stem cell transplantation for a wider patient population. One Sentence SummaryGenetic inhibition of JARID2 enhances repopulating activity of human hematopoietic stem and progenitor cells in vivo via STAT1 upregulation.

developmental biology↗

bioRxiv2025

Network Modeling Predicts How DYRK1A Inhibition Promotes Cardiomyocyte Cycling after Ischemic/Reperfusion Injury

The adult mammalian heart has a limited ability to regenerate lost myocardium following myocardial infarction (MI), largely due to the poor proliferative capacity of cardiomyocytes (CMs). Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a known regulator of cell quiescence, though the mechanisms underlying its function remain unclear. Previous studies have shown that pharmacological inhibition of DYRK1A using harmine induces CM cell cycle re-entry after ischemia/reperfusion (I/R) MI. Here, we developed a computational network model of DYRK1A-mediated regulation of the cell cycle, which predicts how DYRK1A inhibition promotes CM re-entry. To validate these predictions, we tested selective DYRK1A inhibitors and observed robust induction of cell cycle activity in neonatal rat cardiomyocytes (NRCMs). Integrating our network model with bulk RNA-sequencing data from DYRK1A inhibitor-treated NRCMs, we identified E2F1 as a key transcriptional driver of cell cycle gene expression. Finally, we demonstrate that both pharmacological and post-developmental inhibition of DYRK1A enhances heart function and increases CM cycling following I/R MI. Our findings suggest that functional recovery induced by small molecule inhibitor of DYRK1A is mediated by the induction of cycling CMs. One Sentence SummaryInhibition of DYRK1A through LCTB-92 induces cardiomyocyte cycling and improved heart function in a mouse model of ischemic/reperfusion injury.

pharmacology and toxicology↗

bioRxiv2025

Dynamic remodeling of the pancreas immune landscape in obesity.

Obesity is a known risk factor for diseases of the pancreas, including diabetes, pancreatic cancer and pancreatitis, but mechanisms remain unclear. To elucidate how obesity impacts pancreatic immune homeostasis, we performed spatial, transcriptomic and functional profiling of human pancreatic immune cells from obese and non-obese organ donors. Obesity was associated with higher density of tissue resident memory T-cells (TRM) in the exocrine pancreas which display high cytotoxic functions and aggregated around macrophages. Single cell sequencing of pancreatic macrophages revealed two main subsets - FOLR2+ CD11c- fetal-derived macrophages with pro-repair and immunoregulatory function and a FOLR2- CD11c+ monocyte-derived macrophages with greater T-cell interactions and pro-inflammatory function. In obesity, the pancreatic macrophage landscape shifts to lower predominance of FOLR2+ CD11c- macrophages and higher FOLR2- CD11c+ macrophages which interact selectively with the TRM and inflamed exocrine epithelium. Together, these results identify macrophage-T cell circuits and immune epithelial interactions that fuel chronic pancreatic inflammation in obesity - a potential unifying mechanism for obesity-related pancreatic diseases.

immunology↗

bioRxiv2025

A spatiotemporal cancer cell trajectory underlies glioblastoma heterogeneity

Cancer cells display highly heterogeneous and plastic states in glioblastoma, an incurable brain tumour. However, how these malignant states arise and whether they follow defined cellular trajectories across tumours is poorly understood. Here, we generated a deep single cell and spatial multi-omic atlas of human glioblastoma that pairs transcriptomic, epigenomic and genomic profiling of 12 tumours across multiple regions. We identify that glioblastoma heterogeneity is driven by spatially-patterned transitions of cancer cells from developmental-like states towards those defined by a glial injury response and hypoxia. This cellular trajectory regionalises tumours into distinct tissue niches and manifests in a molecularly conserved manner across tumours as well as genetically distinct tumour subclones. Moreover, using a new deep learning framework to map cancer cell states jointly with clones in situ, we show that tumour subclones are finely spatially intermixed through glioblastoma tissue niches. Finally, we show that this cancer cell trajectory is intimately linked to myeloid heterogeneity and unfolds across regionalised myeloid signalling environments. Our findings define a stereotyped trajectory of cancer cells in glioblastoma and unify glioblastoma tumour heterogeneity into a tractable cellular and tissue framework.

cancer biology↗

bioRxiv2025

A selective inhibitor of oncogenic JNK signalling perturbs metastatic outgrowth of triple-negative breast cancer through metabolic blockade

Although c-Jun N-terminal Kinase (JNK) represents an attractive anti-cancer target, its pleiotropic functionality limits the use of direct JNK inhibitors. Here, we identify a distinct subcellular pattern of JNK activity as a therapeutic vulnerability in breast cancer, where cytoplasmic JNK activity predicts poor survival outcomes, is elevated in triple-negative breast cancers (TNBC) and is essential for metastatic outgrowth. Mechanistic analyses reveal cytoplasmic JNK acts through multiple mechanisms, with downstream targets involved in cellular metabolism and cytoskeletal regulation. On this basis, we leveraged actin-based phenotypic drug-screening and identified K12, an indirect but selective inhibitor of cytoplasmic JNK that blocks TNBC metastatic outgrowth in vivo. We reveal that K12 inhibits glutaminase-1 and the pyruvate dehydrogenase complex, and that this poly-pharmacology overcomes pyruvate anaplerosis, a known resistance mechanism of existing glutaminase inhibitors. These findings demonstrate the potential of selectively targeting the oncogenic function of JNK, offering new treatment options for early-stage metastatic TNBC.

cancer biology↗

bioRxiv2025

Runx1 and Runx2 act in concert to suppress Wnt/β-catenin-driven mammary tumourigenesis

The genes encoding transcription factor RUNX1 and its binding partner CBFB have been reported to be mutated in human breast cancer. Here, we provide evidence that Runx1 loss of function results in accelerated disease onset and tumour development in mouse models of breast cancer, in keeping with a tumour suppressor role for RUNX1 in this disease setting. Combined deletion of Runx1 and the related family member Runx2 resulted in mammary epithelial cells becoming exquisitely sensitive to WNT-driven transformation, with the emergence of multiple tumours early in life. Clonogenic assays indicated that Runx1 ablation induced a stem cell like phenotype in mammary epithelial cells, whilst transcriptome analysis demonstrated activation of multiple oncogenic pathways, especially when Runx2 was co- deleted. Interestingly, altered Runx expression in the mammary epithelium also drove profound alterations in the tumour microenvironment, impacting the immune landscape. These results highlight that Runx1 restricts some forms of breast cancer and inhibits the full oncogenic potential of aberrant WNT signalling. Loss of Runx2 itself did not result in tumour promotion, yet the dramatic effects of combined Runx1 and Runx2 loss suggest that Runx2 can substitute for Runx1 in dampening the oncogenic effects of WNT signalling.

cancer biology↗

bioRxiv2025

Plasmid copy number variation impacts pathogenicity and quantification of Curtobacterium flaccumfaciens pv. flaccumfaciens infecting mung bean

In bacteria, plasmids can confer the ability to cause disease. Although they can potentially vary in copy number, little has been reported on the dynamics of plasmids in plant pathogenic bacteria. Pathogenicity of the bacterium Curtobacterium flaccumfaciens pv. flaccumfaciens (Cff), which causes foliar disease on leguminous crops, including mung bean (Vigna radiata), has previously been linked to a plasmid. This study explored the variation in plasmid copy number among a genetically diverse collection of 25 Cff isolates using purposely designed quantitative PCR assays for chromosomal and plasmid DNA targets. Pathogenicity and virulence of six Cff isolates, including one plasmid-free isolate, were assessed on the susceptible mung bean cultivar Opal-AU using visual symptoms, trifoliate dry weights and Cff DNA quantities following stem inoculation. Plasmid copy numbers varied significantly (p <0.001) among plasmid-carrying isolates, ranging from 1.37 to 2.74. For subsequent quantification in planta, the single-copy chromosomal PCR target gene, gyrase b, was selected. Mung beans inoculated with plasmid-carrying isolates exhibited significant variation in visual symptoms (p <0.001), while trifoliate dry weights and Cff DNA quantities did not significantly differ. The treatment using a plasmid-free isolate was not significantly different from the negative control for each of the disease traits. Knowledge of plasmid dynamics in Cff populations lays a foundation for improved understanding of the inheritance and impact of plasmid-related traits. The quantification assays will be useful for monitoring Cff populations and the demonstrated variation in pathogenicity and virulence can assist efforts to breed host plant germplasm with reduced susceptibility to Cff.

pathology↗

bioRxiv2024

Clonal expansion from standing genetic variation underpins the evolution of an emerging plant pathogen in Australia

Pathogens can evolve rapidly, leading to the emergence of novel strains that can overcome commercially deployed host plant resistance. Understanding the genetic and phenotypic diversity and population dynamics of plant pathogens is crucial to inform breeding programs targeting resistance. Tan spot, otherwise known as bacterial wilt, caused by Curtobacterium flaccumfaciens pv. flaccumfaciens, is a destructive disease of mungbean in Australia. Since the 1990s, several mungbean cultivars with partial resistance to tan spot have been released; however, cultivars initially rated as moderately resistant were later rated as moderately susceptible to tan spot. This study investigated the genetic and phenotypic diversity and temporal evolutionary dynamics of C. flaccumfaciens pv. flaccumfaciens in Australian mungbean fields. Whole-genome sequencing of 119 isolates collected from mungbean and other legumes (1986-2019) enabled analyses of pathogen evolution in Australia and in a global context. Results revealed that clonal expansion from standing genetic variation, rather than introduction of novel genotypes, has driven the evolution of this pathogen in Australia since the 1980s. Glasshouse trials confirmed the role of a plasmid in pathogenicity of C. flaccumfaciens pv. flaccumfaciens but found no significant differences in aggressiveness between clonal lineages. This study underscores the importance of understanding pathogen diversity and aggressiveness to guide breeding programs for effective and durable disease resistance and highlights the need for further studies on the competitive fitness of isolates and characterisation of private alleles linked to dominant clonal lineages. SignificanceTan spot is an increasingly significant pathogen affecting beans and mungbean worldwide, with a broad host range and quarantine importance in many countries underscoring the need for effective breeding strategies to manage the disease. Our research provides insights into genetic and phenotypic diversity of this important plant pathogen and temporal changes in its population structure in Australia, which are crucial for developing informed breeding strategies and managing the spread and impact of the disease. This work also underscores the critical need for robust, validated screening protocols and selection of aggressive, locally representative isolates for resistance breeding to ensure accurate assessment of resistance in crops for effective and durable resistance.

evolutionary biology↗