Biology subjects

Morris, K.

Publications and source records attributed to Morris, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Water plant functional groups: a trait-based classification database for Australian plants

Trait-based functional classifications of species offer improved generality in predicting responses to environmental conditions. Water plant functional groups (WPFG) are one such classification. Grouping plant species based on traits associated with germination, growth and reproductive requirements, WPFG have proven useful in examining plant trait-hydrological relationships in aquatic plant research in Australia. Here, we collate existing information from across academic, government and personal databases to create the most comprehensive compilation of plant taxa assignments to WPFG available. Taxonomic nomenclature was first standardized using accepted names under the Australian Plant Census/Australian Plant Name Index. We then assessed agreement among source classifications and derived a consensus-weighted fuzzy classification that retains uncertainty in WPFG assignment at both the species- and genus-level. The resulting database provides evidence-based classifications for the most commonly observed water plants in temperate Australia, including evidence of affinity to all functional groups. This approach supports greater consistency, transparency and reproducibility in WPFG assignment across studies while allowing users to select the level of classification most appropriate to their application. The database is freely available for download from the Zenodo digital repository.

ecology↗

bioRxiv2026

A Brainwide Atlas of Synaptic Nanoarchitecture Across the Mouse Lifespan

How biological complexity emerges from the ordered assembly of molecular building blocks into supramolecular systems remains a central question, particularly in the mammalian brain with its vast synaptic diversity. We introduce NanoSYNMAP, a genetic, optical, and computational platform that integrates FRET with synaptome mapping to quantify nanoscale proximity of proteins in individual synapses brain-wide. We generate the first brain atlas of synaptic nanoarchitecture, based on the proximity of postsynaptic MAGUK supercomplexes. This reveals a molecular logic in which spacing of supramolecular assemblies specifies nanoscale architecture that organizes the global synaptome architecture. Nanoarchitecture varies across brain regions, differentiates during postnatal development, and remodels with aging. Supercomplex proximity reflects scaffold abundance, nanodomain organization, and competitive interactions among MAGUK assemblies. Deletion of a neuropsychiatric risk gene triggers widespread reorganization of nanoscale architecture. These findings establish molecular proximity as a fundamental scalable dimension of synapse diversity in health and disease.

neuroscience↗

bioRxiv2026

Engineering Functionality-Optimized Fully Human B7-H3 CAR T Cells for Enhanced Solid Tumor Therapy

B7-H3 is a cell surface protein overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR) T cell therapy. The most clinically advanced B7-H3 CARs are derived from murine monoclonal antibodies (mAbs) 376.96 and MGA271, which are now in phase 1/11 trials. However, non-human mAb sequences can provoke immune responses, leading to CAR T-cell rejection and therapeutic failure. Although scFv humanization reduces this risk, residual foreign residues within the variable domains remain. To overcome this limitation, we used in vitro phage display to generate fully human B7-H3-specific scFvs for CAR design. In pancreatic cancer, neuroblastoma, and glioblastoma xenograft models, CAR T cells incorporating the lead human binder Y111 were well tolerated and demonstrated superior antitumor activity compared with 376.96- and MGA271-based CARs. Y111 CAR treatment induced complete responses, tumor rejection, and significant survival benefits, identifying Y111 as a promising fully human B7-H3 CAR for solid tumors.

immunology↗

bioRxiv2025

Reconstructing a physiological state space via chronic jugular microdialysis in freely moving mice

Maintaining physiological homeostasis requires a complex interplay among endocrine organs, peripheral tissues, and distributed neuroendocrine control circuits, all of which are coupled through feedback loops that operate over minutes to hours. Although many physiological needs are broadcast through hormones, metabolites, and other chemical compounds circulating in the bloodstream, we rarely observe more than a few of these messengers together and at high cadence during behavior. To address this, we developed a minimally disruptive workflow to measure the free fraction of hundreds of amines and small peptides at a 7.5-minute cadence for [~]8 hrs in freely moving mice using chronic jugular microdialysis implants and chemical isotope labeling Liquid Chromatography-Mass Spectrometry. Single-compound profiles behave according to known physiology, such as purine turnover correlating with movement, delayed histamine/5-HIAA changes, and coordinated amino-acid dynamics. Our multiplexed measures enable high-dimensional analyses that uncover properties of the underlying dynamics. For example, systems-level analyses show that 10 dimensions explain over 70% of the variance in hormone/metabolite covariation, consistent with a low rank description of the physiological state space, with projections aligned to locomotion state transitions. Our work opens avenues for the discovery of hormonal dynamics, compound interactions, and their effects on behavior.

physiology↗

bioRxiv2025

A shared DNA-repeat toxicity threshold, reached somatically at cell-type-specific rates, unites cortical and striatal neurodegeneration in Huntingtons disease

Huntingtons disease (HD) affects two major brain areas - the striatum and cerebral cortex - in ways that differ in timing, severity, and gene-expression changes. For these reasons, and because many cortical neurons project axons to the affected striatal neurons, striatal and cortical atrophy have long been proposed to have distinct mechanisms, with one potentially a secondary consequence of the other. In the striatum, we recently found that neurons degenerate asynchronously as their own huntingtin (HTT) gene CAG-repeat tracts, typically inherited at 40-50 CAGs, expand somatically beyond 150 CAGs. To ask whether a similar or different dynamic affects the cerebral cortex, we analyzed HTT CAG repeats and genome-wide RNA expression together in more than 130,000 nuclei from 12 cortical areas of brain donors with HD. The resulting data revealed that cortical and striatal neurodegeneration in fact result from analogous sequences of cell-autonomous events, each instructed by somatic expansion of a neurons own HTT CAG repeat. Analyses revealed that somatic expansion beyond a high toxicity threshold (of about 150 CAGs) is necessary and sufficient to initiate pathological changes; that this pathogenicity length threshold is shared by striatal and cortical projection neurons of all types; and that cortical area, cortical layer, and axonal projections play only incidental roles, as proxies for the true driver: profound (up to 50-fold) variation among types and subtypes of pyramidal neurons in the likelihood of reaching the 150-CAG toxicity threshold in a human lifetime. These results also suggest that containing somatic DNA-repeat expansion below this high toxicity threshold would protect both brain areas in HD.

genetics↗

bioRxiv2025

Detergent-Triggered Membrane Remodelling Monitored via Intramembrane Fluorescence De-Quenching

Detergent-induced membrane solubilization is important for several biotechnological applications including membrane protein isolation, cell lysis and virus inactivation. The thermodynamic details of the underlying process have been previously examined, but the mechanistic details remain largely underexplored owing in part, to a lack of suitable technologies capable of assessing nanoscopic membrane disruption events. Key open questions include: how do detergents remodel the membrane structure at sub-solubilizing concentrations? And what is the sequence of morphological transitions that lead up to solubilization? Here, we introduce a single-colour assay based on the fluorescence de-quenching of membrane-integrated fluorophores as a sensitive and generalizable tool to probe nanoscale membrane remodelling events induced by detergents. We demonstrate, using fluorescence spectroscopy and time-correlated single photon counting, that the widely used detergent Triton X-100 triggers substantial morphological changes at concentrations below its critical micellar concentration. Moreover, by taking advantage of single vesicle fluorescence lifetime imaging and scanning electron microscopy, we reveal that the swelling step involves a morphological transition from spherical vesicles to toroidal structures, providing direct evidence for detergent-driven membrane reorganization prior to solubilization. Our findings support and refine a multistep model of detergent-induced membrane solubilization, positioning fluorescence de-quenching as a tool for detecting conformational intermediates. We show that the fluorescence de-quenching approach performs robustly across multiple cyanine-based probes and experimental conditions and its nanoscale sensitivity provides a platform from which to interrogate membrane perturbations induced by a wide variety of molecular disruptors, including those with important biomedical significance.

biophysics↗

bioRxiv2025

Experimental flooding impacts soil biogeochemistry but not aboveground vegetation in a coastal forest

Rising sea levels and intensifying storms increase flooding pressure on coastal forests, triggering tree mortality, ecosystem transitions, and changes to the coastal carbon cycle. However, the mechanisms that drive coastal forest mortality remain elusive due to the complex interplay between belowground and aboveground processes during flooding disturbances and limitations of observations typically reported in coastal forest mortality studies. We used an ecosystem-scale manipulation to simulate hurricane-level flooding of a coastal forest. Monitoring real-time soil conditions and tree physiological responses, we observed consistent impacts on soil biogeochemistry aligned with belowground drivers of tree mortality, but no consistent responses in aboveground vegetation. Our findings provide unprecedented empirically based insight into the earliest stages of a hypothesized forest mortality spiral and offer critical benchmarks for predicting coastal forest resilience in the face of accelerating climate change. Significance StatementChanging sea levels and storms are causing more flooding in coastal forests. This flooding kills trees, changing how coastal ecosystems function, but we do not fully understand what factors determine whether forests survive flooding. We designed an ecosystem-scale experiment to answer this question, with controlled saltwater and freshwater floods equivalent to a hurricane in experimental forest plots. Flooding quickly changed soil conditions, but we have not yet observed consistent tree stress responses. Our study provides the most detailed measurements to date of how coastal forests respond to flooding in real time. These findings will help us better understand the early mechanisms and warning signs of forests threatened by flooding.

systems biology↗

bioRxiv2024

3D super-resolution imaging of PSD95 reveals an abundance of diffuse protein supercomplexes in the mouse brain

PSD95 is an abundant scaffolding protein that assembles multiprotein complexes controlling synaptic physiology and behavior. Confocal microscopy has previously shown that PSD95 is enriched in the postsynaptic terminals of excitatory synapses and 2D super-resolution microscopy further revealed that it forms nanoclusters. In this study, we utilized 3D super-resolution microscopy to examine the nanoarchitecture of PSD95 in the mouse brain, characterizing over 8 million molecules. While we were able to identify structural subtypes previously reported, imaging in 3D allowed us to classify these with higher accuracy. Furthermore, 3D super-resolution microscopy enabled the quantification of protein levels, revealing an abundance of PSD95 molecules existed outside of synapses as a diffuse population of supercomplexes, containing multiple copies of PSD95. Further analysis of the supercomplexes containing two units identified two populations: one that had PSD95 molecules separated by 39 {+/-} 2 nm, and a second with a separation of 94 {+/-} 27 nm. These results suggest that PSD95 supercomplexes containing multiple protein copies assemble outside the synapse and then integrate into the synapse to form a supramolecular nanocluster architecture.

biophysics↗

bioRxiv2024

Human induced pluripotent stem cell-derived microglia contribute to thepathophysiology of Fragile X syndrome via increased RAC1 signaling

Fragile X syndrome (FXS) is one of the most common monogenic causes of neurodevelopmental disorders characterized by intellectual disability, autism and epilepsy. Emerging evidence suggests a role for immune dysfunction in autism. Using induced pluripotent stem cell (iPSC)-derived microglial cells from FXS patients (mFXS-MG) and FMR1-deficient microglia from FMR1-knock out human embryonic stem cells (FMR1 KO-MG), we show that loss-of-function of Fragile X Messenger Ribonucleoprotein (FMRP) leads to cell autonomous phagocytic deficits and a proinflammatory state in microglia when compared to gene-corrected controls. Moreover, increased RAC1 signaling in mFXS-MG and FMR1 KO-MG results in increased actin polymerization and enhanced activation of NF-{kappa}B signaling. Exposure of control iPSC-derived cortical neuron cultures to conditioned medium from proinflammatory mFXS-MG results in hyperexcitability. Importantly, pharmacological inhibition of RAC1 signaling in mFXS-MG attenuates their proinflammatory profile and corrects the neuronal hyperexcitability caused by the conditioned medium. Our results suggest that microglia impair neuronal function in FXS, which can be prevented by targeting of RAC1 signaling. Significance statementFXS is one of the most common monogenic causes of neurodevelopmental disorders characterized by intellectual disability, autism, epilepsy and has been associated with immune dysfunction. We therefore generated brain macrophages (microglia) from patient-derived induced pluripotent stem cells (mFXS-MG) and an embryonic stem cell line deficient in the Fragile X messenger ribonucleoprotein 1 (FMR1 KO-MG). We find enhanced activation of RAC1 signaling resulting in phagocytic deficits and immune activation of mFXS-MG and FMR1 KO-MG. Exposure of control iPSC-derived cortical neurons to conditioned medium from proinflammatory mFXS-MG results in neuronal hyperexcitability, which can be prevented by pharmacological RAC1 inhibition in mFXS-MG. We conclude that RAC1 signaling in microglia could be a potential therapeutic target in FXS.

neuroscience↗

bioRxiv2024

Long somatic DNA-repeat expansion drives neurodegeneration in Huntington disease

Huntington Disease (HD) is a fatal genetic disease in which most striatal projection neurons (SPNs) degenerate. The central biological question about HD pathogenesis has been how the disease-causing DNA repeat expansion (CAGn) in the huntingtin (HTT) gene leads to neurodegeneration after decades of apparent latency. Inherited HTT alleles with a longer CAG repeat hasten disease onset; the length of this repeat also changes over time, generating somatic mosaicism, and genes that regulate DNA-repeat stability can influence HD age-at-onset. To understand the relationship between a cells CAG-repeat length and its biological state, we developed a single-cell method for measuring CAG-repeat length together with genome-wide RNA expression. We found that the HTT CAG repeat expands from 40-45 CAGs to 100-500+ CAGs in HD-vulnerable SPNs but not in other striatal cell types, with these long DNA-repeat expansions acquired at different times by individual SPNs. Surprisingly, somatic expansion from 40 to 150 CAGs had no apparent effect upon gene expression - but neurons with 150-500+ CAGs shared profound gene-expression changes. These expression changes involved hundreds of genes, escalated alongside further CAG-repeat expansion, eroded positive and then negative features of neuronal identity, and culminated in expression of senescence/apoptosis genes. Rates of striatal neuron loss across HD stages reflected the rates at which neurons entered this biologically distorted state. Our results suggest that HTT CAG repeats in striatal neurons undergo decades of biologically quiet expansion, then, as they asynchronously cross a high threshold, cause SPNs to degenerate quickly and asynchronously. We conclude that, at any moment in the course of HD, most neurons have an innocuous (but unstable) huntingtin gene, and that HD pathogenesis is a DNA process for almost all of a neurons life.

genetics↗

bioRxiv2023

The organisation and turnover of synaptic proteins within molecular supercomplexes.

The concept that dimeric protein complexes in synapses can sequentially replace their subunits has been a cornerstone of Francis Cricks 1984 hypothesis, explaining how long-term memories could be maintained in the face of short protein lifetimes. However, it is unknown whether the subunits of protein complexes that mediate memory are sequentially replaced in the brain and if this process is linked to protein lifetime. We address these issues by focusing on supercomplexes assembled by the abundant postsynaptic scaffolding protein PSD95, which plays a crucial role in memory. We used single-molecule detection, super-resolution microscopy and MINFLUX to probe the molecular composition of PSD95 supercomplexes in mice carrying genetically encoded HaloTags, eGFP and mEos2. We found a population of PSD95-containing supercomplexes comprised of two copies of PSD95, with a dominant 12.7 nm separation. Time-stamping of PSD95 subunits in vivo revealed that each PSD95 subunit was sequentially replaced over days and weeks. Comparison of brain regions showed subunit replacement was slowest in the cortex, where PSD95 protein lifetime is longest. Our findings reveal that protein supercomplexes within the postsynaptic density can be maintained by gradual replacement of individual subunits providing a mechanism for stable maintenance of their organization. Moreover, we extend Cricks model by suggesting that synapses with slow subunit replacement of protein supercomplexes and long protein lifetimes are specialized for long-term memory storage and that these synapses are highly enriched in superficial layers of the cortex where long-term memories are stored.

neuroscience↗

bioRxiv2023

The spatially resolved tumor microenvironment predicts treatment outcome in relapsed/refractory Hodgkin lymphoma

PURPOSEAbout a third of relapsed or refractory classic Hodgkin lymphoma (r/r CHL) patients succumb to their disease after high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT). Here, we aimed to describe spatially resolved tumor microenvironment (TME) ecosystems to establish novel biomarkers associated with treatment failure in r/r CHL. METHODSWe performed imaging mass cytometry (IMC) on 169 paired primary diagnostic and relapse biopsies using a marker panel specific for CHL biology. For each cell type in the TME, we calculated a spatial score measuring the distance of nearest neighbor cells to the malignant Hodgkin Reed Sternberg cells within close interaction range. Spatial scores were used as features in prognostic model development for post-ASCT outcomes. RESULTSHighly multiplexed IMC data revealed shared TME patterns in paired diagnostic and early relapse/refractory CHL samples, whereas TME patterns were more divergent in pairs of diagnostic and late relapse samples. Integrated analysis of IMC and single cell RNA sequencing data identified unique architecture defined by CXCR5+ HRS cells and their strong spatial relationship with CXCL13+ macrophages in the TME. We developed a prognostic assay ( RHL4S) using four spatially resolved parameters, CXCR5+ HRS cells, PD1+CD4+ T cells, tumor-associated macrophages, and CXCR5+ B cells, which effectively separated patients into high-risk vs low-risk groups with significantly different post-ASCT outcomes. The RHL4S assay was validated in an independent r/r CHL cohort using a multicolor immunofluorescence assay. CONCLUSIONSWe identified the interaction of CXCR5+ HRS cells with ligand-expressing CXCL13+ macrophages as a prominent crosstalk axis in relapsed CHL. Harnessing this TME biology, we developed a novel prognostic model applicable to r/r CHL biopsies, RHL4S, opening new avenues for spatial biomarker development.

cancer biology↗

bioRxiv2022

Structural conversion of α-synuclein at the mitochondria induces neuronal toxicity

Aggregation of -Synuclein (-Syn) drives Parkinsons disease, although the initial stages of self-assembly and structural conversion have not been captured inside neurons. We track the intracellular conformational states of -Syn utilizing a single-molecule FRET biosensor, and show that -Syn converts from its monomeric state to form two distinct oligomeric states in neurons in a concentration dependent, and sequence specific manner. 3D FRET-CLEM reveals the structural organization, and location of aggregation hotspots inside the cell. Notably multiple intracellular seeding events occur preferentially on membrane surfaces, especially mitochondrial membranes. The mitochondrial lipid, cardiolipin triggers rapid oligomerization of A53T -Syn, and cardiolipin is sequestered within aggregating lipid-protein complexes. Mitochondrial aggregates impair complex I activity and increase mitochondrial ROS generation, which accelerates the oligomerization of A53T -Syn, and ultimately causes permeabilization of mitochondrial membranes, and cell death. Patient iPSC derived neurons harboring A53T mutations exhibit accelerated oligomerization that is dependent on mitochondrial ROS, early mitochondrial permeabilization and neuronal death. Our study highlights a mechanism of de novo oligomerization at the mitochondria and its induction of neuronal toxicity.

neuroscience↗

bioRxiv2021

A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle delivery system. Multiple small-interfering RNAs (siRNAs) targeting highly conserved regions of the SARS-CoV-2 virus were screened and three candidate siRNAs emerged that effectively inhibit virus by greater than 90% either alone or in combination with one another. We simultaneously developed and screened two novel lipid nanoparticle formulations for the delivery of these candidate siRNA therapeutics to the lungs, an organ that incurs immense damage during SARS-CoV-2 infection. Encapsulation of siRNAs in these LNPs followed by in vivo injection demonstrated robust repression of virus in the lungs and a pronounced survival advantage to the treated mice. Our LNP-siRNA approaches are scalable and can be administered upon the first sign of SARS-CoV-2 infection in humans. We suggest that an siRNA-LNP therapeutic approach could prove highly useful in treating COVID-19 disease as an adjunctive therapy to current vaccine strategies.

synthetic biology↗

bioRxiv2020

Differential activity and expression of human 5β-reductase (AKR1D1) splice variants

Steroid hormones, including glucocorticoids and androgens, exert a wide variety of effects in the body across almost all tissues. The steroid A-ring 5{beta}-reductase (AKR1D1) is expressed in human liver and testes, and three splice variants have been identified (AKR1D1-001, AKR1D1-002, AKR1D1-006). Amongst these, AKR1D1-002 is the best described; it modulates steroid hormone availability and catalyses an important step in bile acid synthesis. However, specific activity and expression of AKR1D1-001 and AKR1D1-006 are unknown. AKR1D1-002, AKR1D1-001 and AKR1D1-006 were measured in human liver biopsies and human hepatoma cell lines by qPCR. Three-dimensional (3D) structures of AKR1D1 variants were determined using in silico approaches. AKR1D1 variants were over-expressed in HEK293 cells, and successful overexpression confirmed by qPCR and western blotting. Steroid hormone clearance was measured by mass spectrometry and ELISA, and steroid receptor activation determined by luciferase reporter assays. AKR1D1-002 and AKR1D1-001 are expressed in human liver, and only AKR1D1-006 is expressed in human testes. Following over-expression in HEK293 cells, AKR1D1-001 and AKR1D1-006 protein levels were lower than AKR1D1-002, but significantly increased following treatment with the proteasomal inhibitor, MG-132. AKR1D1-002 efficiently metabolised glucocorticoids and androgens and decreased receptor activation. AKR1D1-001 and AKR1D1-006 poorly metabolised dexamethasone, but neither protein metabolised cortisol, prednisolone or testosterone. We have demonstrated the differential expression and role of AKR1D1 splice variants to regulate steroid hormone clearance and receptor activation. AKR1D1-002 is the predominant functional protein in steroidogenic and metabolic tissues. In addition, AKR1D1-001 and AKR1D1-006 may have a limited role in the regulation of synthetic glucocorticoid action.

molecular biology↗

bioRxiv2020

The Mechanism of Vesicle Solubilization by the Detergent Sodium Dodecyl Sulfate

Membrane solubilization by sodium dodecyl sulfate (SDS) is indispensable for many established biotech-nological applications, including viral inactivation and protein extraction. Although the ensemble thermo-dynamics have been thoroughly explored, the underlying molecular dynamics have remained inaccessible, owing to major limitations of traditional measurement tools. Here, we integrate multiple advanced biophysical approaches to gain multi-angle insight into the time-dependence and fundamental kinetic steps associated with the solubilization of single sub-micron sized vesicles in response to SDS. We find that the accumulation of SDS molecules on in-tact vesicles triggers biphasic solubilization kinetics comprising an initial vesicle expansion event followed by rapid lipid loss and micellization. Our findings support a general mechanism of detergent-induced membrane solubilization and we expect the framework of correlative biophysical technologies presented here will form a general platform for elucidating the complex kinetics of membrane perturbation induced by a wide variety of surfactants and disrupting agents.

biophysics↗

bioRxiv2019

Kinetics of the immune response to Eimeria maxima in relatively resistant and susceptible chicken lines

Eimeria maxima is a common cause of coccidiosis in chickens, a disease which has a huge economic impact on poultry production. Knowledge of immunity to E. maxima and the specific mechanisms that contribute to differing levels of resistance observed between chicken breeds and between congenic lines derived from a single breed of chickens is required. This study aimed to define differences in the kinetics of the immune response of two inbred lines of White Leghorn chickens that exhibit differential resistance (line C.B12) or susceptibility (line 15I) to infection by E. maxima. Line C.B12 and 15I chickens were infected with E. maxima and transcriptome analysis of infected jejunal tissue was carried out at 2, 4, 6 and 8 days post-infection (dpi). RNA-Seq analysis revealed differences in the rapidity and magnitude of cytokine transcription responses post-infection between the two lines. In particular, IFN-{gamma} and IL-10 transcripts in the jejunum accumulated earlier in line C.B12 (at 4 dpi) compared to line 15I (at 6 dpi). Line C.B12 chickens exhibited increases of IFNG and IL10 mRNA in the jejunum at 4 dpi, whereas in line 15I transcription was delayed but increased to a greater extent. RT-qPCR and ELISAs confirmed the results of the transcriptomic study. Higher serum IL-10 correlated strongly with higher E. maxima replication in line 15I compared to line C.B12 chickens. Overall, the findings suggest early induction of the IFN-{gamma} and IL-10 responses, as well as immune-related genes at 4 dpi identified by RNA-Seq, may be key to resistance to E. maxima.

immunology↗

bioRxiv2019

The quail as an avian model system: its genome provides insights into social behaviour, seasonal biology and infectious disease response

The Japanese quail (Coturnix japonica) is a popular domestic poultry species and an increasingly significant model species in avian developmental, behavioural and disease research. We have produced a high-quality quail genome sequence, spanning 0.93 Gb assigned to 33 chromosomes. In terms of contiguity, assembly statistics, gene content and chromosomal organization, the quail genome shows high similarity to the chicken genome. We demonstrate the utility of this genome through three diverse applications. First, we identify selection signatures and candidate genes associated with social behaviour in the quail genome, an important agricultural and domestication trait. Second, we investigate the effects and interaction of photoperiod and temperature on the transcriptome of the quail medial basal hypothalamus, revealing key mechanisms of photoperiodism. Finally, we investigate the response of quail to H5N1 influenza infection. In quail lung, many critical immune genes and pathways were downregulated, and this may be key to the susceptibility of quail to H5N1. This genome will facilitate further research into diverse research questions using the quail as a model avian species.

genomics↗