Biology subjects

Wilson, I.

Publications and source records attributed to Wilson, I..

14 recordsLinked to original sources

bioRxiv2026

Monotreme transcriptomes shed light on evolution of lactation and placentation

Placentation and lactation are hallmark mammalian reproductive traits and key processes facilitating the transfer of nutrients from the mother to the offspring. The basal mammalian lineage of egg-laying monotremes features a short gestation period supported by a simple placenta and an elongated lactation, similar to marsupials. Eutherian mammals by contrast evolved longer gestation facilitated by extensive placentation and shorter lactation. To understand the gene expression underpinning maternal-foetal nutrient transfer across mammals, we generated transcriptome datasets for the monotreme reproductive tract and mammary gland and compared this to expression in representative species from the other mammalian clades: marsupials (Tammar wallaby) and eutherians (mouse). This revealed extensive overlapping gene expression between the therian placenta and monotreme reproductive tract, including the first observation of retroviral gene expression in the echidna reproductive tract. Interestingly, we discovered that transport and development functions supporting foetal growth are expressed in echidna mammary gland and eutherian placenta, likely a signature of the shift from prolonged lactation to longer placentation. Together, this demonstrates that diverse modes of maternal-foetal nutrient transfer are underpinned by similar gene networks across mammals.

evolutionary biology↗

bioRxiv2026

Immune-metabolic PET/MRI uncovers microenvironmental reprogramming under combined immunotherapy and anti-angiogenic therapy

The limited efficacy of immune checkpoint inhibitor (ICI) therapy in triple-negative breast cancer (TNBC) highlights the need for combination strategies that enhance antitumor responses. Sorafenib, a multikinase inhibitor with anti-angiogenic and immunomodulatory activity, represents a rational partner for ICI-based combination therapy. However, therapeutic responses to such combinations are biologically complex and cannot be fully characterized by any single biomarker or imaging modality. Here, we evaluated ICI therapy combined with sorafenib in the aggressive and ICI-refractory orthotopic 4T1 TNBC model. Therapeutic responses were assessed using a unique longitudinal multimodal imaging framework integrating [Zr]Zr-DFO-anti-CD8 minibody and [{superscript 1}F]FDG PET, as well as perfluorocarbon (PFC)-based {superscript 1}F MRI and hyperpolarized {superscript 1}3C MRS, together with ex vivo analyses. Only the ICI-sorafenib combination suppressed tumor growth, whereas both monotherapies showed limited antitumor activity. Multimodal imaging, together with complementary ex vivo analyses, uncovered coordinated tumor microenvironment (TME) remodeling, including vascular normalization, elevated CD8 cell presence with modest enrichment in the tumor center, delayed increase in phagocyte-associated {superscript 1}F MRI signal coupled with reduced CD206 cell infiltration, and sustained metabolic activity. These findings support ICI-sorafenib combination therapy as a promising therapeutic strategy for TNBC. Therapeutic efficacy reflected coordinated vascular, immune, and metabolic remodeling. This multimodal imaging framework enables non-invasive longitudinal monitoring of these complementary TME changes, providing a comprehensive strategy for treatment assessment in immunotherapy-based combination therapies. One Sentence SummaryLongitudinal multimodal imaging identified a multidimensional TME response signature of effective ICI-sorafenib therapy in TNBC.

cancer biology↗

bioRxiv2026

Protective pan-betacoronavirus neutralizing antibodies by vaccination

The continued emergence of betacoronaviruses underscores the urgent need for vaccines that provide broadly protective immunity. Here, we present an epitope-focused vaccine strategy targeting the conserved S2 stem-helix region of the spike fusion machinery, a broadly neutralizing antibody-(bnAb) epitope shared across betacoronaviruses yet partially occluded on the native spike. Immunization of non-human primates with engineered S2 stem-helix nanoparticle immunogens, alone or followed by a SARS-CoV-2 BA.1 spike mRNA boost, elicited broadly cross-reactive antibody responses against sarbecoviruses, merbecoviruses, and embecoviruses and neutralized SARS-CoV-2, multiple variants, other sarbecoviruses, and MERS-CoV. Vaccine-elicited monoclonal antibodies displayed broad in-vitro neutralizing activity and protected against both SARS-CoV-2 and MERS-CoV in-vivo. Structural analyses revealed conserved features between rhesus and human stem-helix bnAbs, supporting the translational potential. Overall, our findings provide proof-of-concept that epitope-focused nanoparticle immunogens can target partially occluded, immunoquiescent bnAb epitopes, laying the groundwork for pan-betacoronavirus vaccines that provide broad protection and strengthen pandemic preparedness. ONE SENTENCE SUMMARYEpitope-focused S2 stem-helix nanoparticle immunogens elicit protective broadly neutralizing antibodies (bnAbs) against diverse betacoronaviruses in non-human primates, establishing a framework for development of pan-betacoronavirus vaccines.

immunology↗

bioRxiv2026

Identification of environmental factors and growth stages in the prediction of fibre yield and fibre quality traits in rain-grown cotton

ContextUnderstanding how and when environmental conditions influence overall crop performance is crucial for optimising the development of genotypes to a specific breeding target environment. We focused on economically important traits of Australian rain-grown cotton including fibre yield and quality traits, which have not been investigated comprehensively. The aim of the study was to identify relevant environmental factors, and the timing and extent of their impact on rain-grown cotton production. MethodsWe used a data driven approach to analyse the relationship between ten climate related environmental factors across various plant growth stages and eight fibre yield and quality traits, using a large-scale field dataset of 9,283 records collected over 23 years at 4 locations, with 53 unique year-location combinations. We applied eight complementary statistical models including stepwise, penalised and Bayesian linear regression, regression-tree based ensemble methods and deep learning frameworks to (1) select the most essential environmental covariates affecting rain-grown cotton production, and (2) evaluate the predictive performance of these models. ResultsThe environmental impacts on rain-grown cotton production were trait and growth-stage specific. Number of rainy days and solar radiation were identified as the most influential environmental factors for fibre yield traits, vapour pressure deficit at maximum daily temperature was the most influential factor for majority of fibre quality traits. However, each analysed trait was influenced by multiple environmental factors across multiple growth stages (rather than a single factor or a single growth stage). These influential covariates explained a wide range of variation in the traits, accounting for 5.8% to 68.2%. Using the best-fit random forest model, our findings revealed non-linear relationships between key environmental covariates and the traits. ConclusionsEnvironmental factors at different rain-grown cotton growth stages are key determinants for the performance of end-of-season fibre yield and fibre quality parameters. These findings highlight the need to account for environment conditions when developing cotton varieties optimised for rain-grown production systems. Potential strategies are proposed whereby these key environmental factors can be used to increase the rate of genetic gain in rain-grown cotton production systems. ImplicationsThe results of this study will be crucial for future genetic evaluations and analyses of genotype-by-environment interaction effects in rain-grown cotton, which must account for the influence of the environment on plant performance. Furthermore, these methods can be applied to other species to identify critical growth stages and environmental factors which most influence crop performance.

bioinformatics↗

bioRxiv2026

Novel linkage disequilibrium-based genotype-by-environmental interaction method for genomic prediction of cotton yield and fibre quality traits

Genomic prediction (GP) across diverse environments has a potential to accelerate genetic gain in cotton breeding programs. A major challenge in GP is modelling genotype-by-environment interactions (GEI), which is essential for selecting stable and high-performing genotypes under variable production conditions. However, incorporating GEI into GP models increases the dimensionality and computational complexity, risking complex models that are impractical to use on commercial breeding-scale data sets because of run times and computational demands. This study addresses two primary aims. Firstly, we evaluate the practical benefits of GEI-informed GP for predicting economically important cotton traits. Second, advanced statistical modelling strategies are developed and assessed for integrating genomic and environmental data at scale. We propose a dimensionality reduction approach that combines linkage disequilibrium network analysis with principal component techniques to reduce redundancy while preserving informative variation. Using this reduced dataset, we implement Bayesian linear regression models and, for comparison, deep residual neural networks for genomic prediction. Analyses were conducted on a large multi-environment dataset from the CSIRO cotton breeding program, comprising 3,236 breeding lines, 54 environmental covariates, and 8,049 yield and fibre quality phenotype records collected over 10 years and 9 locations representing 41 year-location combinations. Results demonstrate that generally Bayesian linear regression approaches outperform BG-BLUP models, with all three linear/linear mixed methods providing clearly more reliable performance than the deep learning models. These findings highlight the value of using interpretable statistical models for integrating genomic and environmental information to support selection decisions under diverse environmental conditions.

plant biology↗

bioRxiv2026

Undergraduate student practicals generate high-quality data for microbiome research

The increasing prominence and accessibility of microbiomics has provided an opportunity for authentic research experiences in the undergraduate practical classroom. In recent years, this approach has contributed to published research projects. However, there is little information evaluating the quality of student-generated data compared to that of trained researchers. To investigate this, we designed an undergraduate practical component in which 37 final-year genetics students generated microbial profiles of 22 echidna scats using matched samples that were also profiled by an experienced researcher. DNA yield, 16S PCR success, sequencing library size and microbial diversity were compared between the groups in order to assess both the ability and accuracy of students in characterising faecal microbiota. Our research revealed that students were able to produce research-grade microbiome data comparable to a postgraduate researcher. Importantly, we found that students did not introduce contamination at a higher rate than the trained researcher. These findings reinforce that the undergraduate classroom is a valuable approach for microbiome research in addition to its benefits for student engagement and experience. The design and successful implementation of these practicals provide a template for a variety of research-led microbiome teaching.

scientific communication and education↗

bioRxiv2025

Evolution and expression of Glial Cells Missing (GCM1 and GCM2) in monotremes suggests an ancient role in reproduction and placentation

The Glial Cells Missing (GCM) genes were first discovered in Drosophila and encode transcription factors important for gliogenesis. In placental mammals, GCM1 regulates several genes that are important for early placenta development, while its paralog GCM2 is important for parathyroid gland development. The egg-laying monotremes, which represent the most diverged extant mammalian lineage, undergo a short period of intrauterine development and form a simple placenta. To gain more insight into the evolution of GCM genes we analysed the sequence, expression, and genomic localization of GCM1 and GCM2 genes in the platypus and echidna. We found that the chromosomal localisation of GCM1 changed after the divergence of therian mammals, coinciding with the evolution of a complex placenta. Expression analysis revealed the presence of GCM transcripts in male and female monotreme gonads, as well as expression of GCM1 in the female reproductive tract. GCM binding sites in target genes associated with placental development in therian mammals were also present in the monotremes and the chicken. Together, this suggests that the role of GCM1 in the placenta emerged early in mammalian evolution.

evolutionary biology↗

bioRxiv2024

Pouch microbiome changes during lactation in the short-beaked echidna (Tachyglossus aculeatus)

Monotreme and marsupial early development is characterised by a short gestation, the birth of the young at an early stage of development, and a long lactation in the pouch or pseudo-pouch. The lack of a functional adaptive immune system in these altricial young raises questions about how they survive in a microbe-rich world. Previous studies on marsupial pouches have revealed changes to pouch microbe composition during lactation but no information is available in monotremes. We investigated changes in the echidna pseudo-pouch microbiome during different stages of the reproductive cycle and whether this differs between wild and zoo-managed animals. Swab samples were obtained from wild and captive echidna pseudo-pouches outside of breeding season, during courtship and breeding, and during lactation. 16S rRNA gene metabarcoding revealed that the pseudo-pouch microbiome undergoes dramatic changes during lactation, with a reduction in bacterial taxa that may be pathogenic. These changes were not observed in samples taken outside of breeding season or during courtship and mating. This showed that the echidna pseudo-pouch environment changes during lactation to accommodate young that lack a functional adaptive immune system. This study pioneers pouch microbiome research in monotremes, provides new biological information on echidna reproduction, and may also provide information about the effects of captive management to inform breeding programs in the future.

genomics↗

bioRxiv2024

Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire

The generation of broadly neutralizing antibodies (bnAbs) to specific HIV epitopes of the HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The current animal models we use have been unable to reliable produce a broadly neutralizing antibody response, with the exception of cows. Cows have rapidly and reliably produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models other engineered immunogens previously have been able to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n=4) with two regiments of V2-apex focusing immunogens to investigate whether antibody responses could be directed to the V2-apex on Env. Group 1 were immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 were immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows respectively. The best bnAbs had both medium breadth and potency. Potent and broad responses developed later than previous CD4bs cow bnAbs and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target multiple broadly neutralizing epitopes on the HIV surface reveals important insight into the generation of immunogens and testing in the cow animal model. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response. Author SummaryThe elicitation of epitope-specific broadly neutralizing antibodies is highly desirable for an HIV vaccine as bnAbs can prevent HIV infection in robust animal challenge models and humans, but to date, cows are the only model shown to reliably produce HIV bnAb responses on Envelope (Env) immunization. These responses involve Abs with ultralong CDRH3s and are all directed to a single site, the CD4 binding site. To determine whether this is a unique phenomenon or whether cow antibodies can target further bnAb sites on Env, we employed an immunization protocol that generated cow bnAbs to a second site, the V2-apex. We conclude that ultralong CDRH3s are well adapted to penetrate the glycan shield of HIV Env and recognize conserved regions and may constitute protein units, either in the context of antibodies or in other engineered proteins, that could be deployed as anti-HIV reagents.

immunology↗

bioRxiv2023

Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2

The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 ([~]4.4%) antibodies isolated at 1.4[~]6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies. One Sentence SummaryExtremely potent pan-sarbecovirus neutralizing antibodies

immunology↗

bioRxiv2020

Quantifying multivariate genotype-by-environment interactions, evolutionary potential and its context-dependence in natural populations of the water flea, Daphnia magna.

Genotype-by-environment interactions (G x E) underpin the evolution of plastic responses in natural populations. Theory assumes that G x E interactions exist but empirical evidence from natural populations is equivocal and difficult to interpret because G x E interactions are normally univariate plastic responses to a single environmental gradient. We compared multivariate plastic responses of 43 Daphnia magna clones from the same population in a factorial experiment that crossed temperature and food environments. Multivariate plastic responses explained more than 30% of the total phenotypic variation in each environment. G x E interactions were detected in most environment combinations irrespective of the methodology used. However, the nature of G x E interactions was context-dependent and led to environment-specific differences in additive genetic variation (G-matrices). Clones that deviated from the population average plastic response were not the same in each environmental context and there was no difference in whether clones varied in the nature (phenotypic integration) or magnitude of their plastic response in different environments. Plastic responses to food were aligned with additive genetic variation (gmax) at both temperatures, whereas plastic responses to temperature were not aligned with additive genetic variation (gmax) in either food environment. These results suggest that fundamental differences may exist in the potential for our population to evolve novel responses to food versus temperature changes, and challenges past interpretations of thermal adaptation based on univariate studies.

evolutionary biology↗

bioRxiv2020

Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines

Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1C modifications in a mucin-deleted form (GP{Delta}muc) increase trimer yield, whereas alterations of HR1C exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GP{Delta}muc trimers in their unliganded state. We then display a modified GP{Delta}muc trimer on reengineered nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display.

microbiology↗

bioRxiv2020

Insights into the salivary N-glycome of Lutzomyia longipalpis, vector of visceral leishmaniasis

During Leishmania transmission sand flies inoculate parasites and saliva into the skin of vertebrates. Saliva has anti-haemostatic and anti-inflammatory activities that evolved to facilitate bloodfeeding, but also modulate the hosts immune responses. Sand fly salivary proteins have been extensively studied, but the nature and biological roles of protein-linked glycans remain overlooked. Here, we characterised the profile of N-glycans from the salivary glycoproteins of Lutzomyia longipalpis, vector of visceral leishmaniasis in the Americas. In silico predictions suggest half of Lu. longipalpis salivary proteins may be N-glycosylated. SDS-PAGE coupled to LC-MS analysis of sand fly saliva, before and after enzymatic deglycosylation, revealed several candidate glycoproteins. To determine the diversity of N-glycan structures in sand fly saliva, enzymatically released sugars were fluorescently tagged and analysed by HPLC, combined with highly sensitive LC-MS/MS, MALDI-TOF-MS, and exoglycosidase treatments. We found that the N-glycan composition of Lu. longipalpis saliva mostly consists of oligomannose sugars, with Man5GlcNAc2 being the most abundant, and a few hybrid-type species. Interestingly, some glycans appear modified with a group of 144 Da, whose identity has yet to be confirmed. Our work presents the first detailed structural analysis of sand fly salivary glycans.

biochemistry↗

bioRxiv2019

Genome-wide changes in genetic diversity in a Myotis lucifugus population affected by white-nose syndrome

Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low FST values within the population across time, i.e. prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history.

evolutionary biology↗