Biology subjects

Wilson, D. R.

Publications and source records attributed to Wilson, D. R..

8 recordsLinked to original sources

bioRxiv2026

Improving peptide vaccine manufacturability without sacrificing immunogenicity: substitution of methionine and cysteine with oxidation-resistant isosteres

AO_SCPLOWBSTRACTC_SCPLOWVaccines comprising peptide antigens for inducing T cell immunity are being developed for a broad range of therapeutic applications including prevention and treatment of cancer, autoimmunity, and infectious diseases. However, many peptide antigens contain cysteine and/or methionine, which are prone to form oxidation products that can present challenges to manufacturing and reduce biological activity. To address this challenge, we introduced oxidation resistant (OXR) antigens wherein the cysteine and methionine residues of naturally occurring, wild type (WT) peptide antigens are substituted with isosteric residues that are structurally related but omit the oxidation-prone sulfur atom. Our results showed that vaccination with OXR antigens substituting cysteine and methionine with isosteres alpha-aminobutyric acid and norleucine, respectively, induced immune responses to the WT antigen that were equivalent or higher than those induced by vaccination with WT antigens. T cell responses were not affected by the position of the amino acid substitutions indicating that the isosteres do not negatively impact major histocompatibility complex (MHC) binding or T cell recognition. The T cells induced were high quality and associated with anti-tumor efficacy in vivo. Interestingly, substitution of cysteine with serine, which replaces the sulfur for an oxygen, did not yield cross-reactive T cell responses, highlighting the high degree of molecular discernment of peptide-MHC processing and presentation. In sum, OXR antigens provide a generalizable strategy for eliminating sulfur oxidation products and improving the manufacturability and shelf-life of peptide-based vaccines without affecting desired biologic activity.

immunology↗

bioRxiv2023

Leach's Storm-Petrels fledge on the full moon and throughout the lunar cycle

Many seabirds are attracted to anthropogenic light, and the risk is greater for recent fledglings. Lunar phase predicts the probability of stranding, but it remains uncertain whether lunar phase is associated with when young seabirds fledge. Fledging behaviour of nocturnal, burrowing seabirds can be difficult to monitor using traditional methods but can provide insight into environmental factors that influence the risk of stranding. We used passive integrated transponder tags to monitor the fledging dates and times of Leachs Storm-Petrel chicks from four breeding seasons at a major colony in Newfoundland and Labrador, Canada. We also assessed whether lunar phase associated with fledging date. The median fledge time was 2.4 h after sunset (1.4 - 12.4 h). The median fledge date was 10 October, and fledging dates ranged from 13 September to 13 November. Most importantly, Leachs Storm-Petrels chicks did fledge during the full moon. These results provide insight into why storm-petrels are less attracted to anthropogenic light during high levels of natural illumination and can be used to inform periods of higher risk for stranding, thus allowing better concentration of conservation efforts.

animal behavior and cognition↗

bioRxiv2022

Vocal traits of shorebird chicks are related to body mass and sex

Acoustic communication is critical during early life phases in precocial birds. For example, adult alarm calls can elicit antipredator behaviour in young, and chick vocalisations can communicate information to parents about chick identity, condition, location, sex, or age. We investigated whether chick calls of two species of Australian Charadriidae vary with sex or body mass. We handled Red-capped Plover Charadrius ruficapillus and Southern Masked Lapwing Vanellus miles novaehollandiae chicks for purposes of measurement, blood sampling, and banding. We opportunistically recorded their distress calls while in the hand, and analysed the calls to determine whether call structure is related to sex or body mass (a proxy for age). We measured five traits per call, plus time intervals between successive calls, for 26 plover chicks (2600 calls) and 95 lapwing chicks (6835 calls). In plovers, inter-call intervals were shorter in males and both inter-call interval and the dominant frequency range of calls decreased with increasing body mass. In lapwings, frequency modulation (computed as the range in the rate of change of the dominant frequency) was lower in male calls. The dominant frequency range of lapwing calls decreased with mass in both sexes, but the decline was greater in males, resulting in a lower dominant frequency range in males. Frequency modulation and entropy of lapwing calls also decreased with increasing body mass. Minimum dominant frequency did not change with body mass or sex in either species. Our study provides the first evidence for charadriid chicks of (a) a sexual difference in call structure and rate and (b) gradual growth-related changes in call structure and rate, across chicks. Studies on calls from a greater range of chick ages and from more species within this large and diverse family would be valuable. We provide a foundation for further studies of shorebird vocalisations during growth, which may elucidate the development and functional significance of such vocalisations.

animal behavior and cognition↗

bioRxiv2018

Is physiological stress state reflected in acoustic structure of vocalizations? An experimental test in wild North American red squirrels

Acoustic signaling is an important means by which animals communicate both stable and labile characteristics. Although it is widely appreciated that vocalizations can convey information on labile state, such as fear and aggression, very few studies have experimentally examined the acoustic expression of short-term stress state. The transmission of such information about physiological state could have broad implications, potentially allowing other individuals to modify their behavior or life history traits in response to this public information. North American red squirrels (Tamiasciurus hudsonicus) produce vocalizations known as rattles that advertise territorial ownership. We examined the influence of changes in physiological stress state on rattle acoustic structure through the application of a stressor (trapping and handling the squirrels) and by provisioning squirrels with exogenous glucocorticoids (GCs). We characterized the acoustic structure of rattles emitted by these squirrels by measuring rattle duration, mean frequency, and entropy. Our results provide mixed evidence that rattles show a \"stress signature\". When squirrels were trapped and handled, they produced rattles that were longer in duration with a higher frequency and increased entropy. However, squirrels that were administered exogenous GCs had similar rattle duration, frequency, and entropy as squirrels that received control treatments and unmanipulated (unfed) squirrels. Our results indicate that short-term stress does affect the acoustic structure of vocalizations, but elevated circulating GC levels are not solely responsible for such changes.

animal behavior and cognition↗

bioRxiv2018

Red squirrels mitigate costs of territory defence through social plasticity

For territorial species, the ability to be behaviourally plastic in response to changes in their social environment may be beneficial by allowing individuals to mitigate conflict with conspecifics and reduce the costs of territoriality. Here we investigated whether North American red squirrels (Tamiasciurus hudsonicus) were able to minimize costs of territory defence by adjusting behaviour in response to the familiarity of neighbouring conspecifics. Since red squirrels living in familiar neighbourhoods face reduced intrusion risk, we predicted that increasing familiarity among territorial neighbours would allow squirrels to spend less time on territorial defence and more time in the nest. Long-term behavioural data (1995-2004) collected from the same squirrels across several different social environments indicated that red squirrels reduced rates of territorial vocalizations and increased nest use in response to increasing familiarity with neighbours. In contrast, cross-sectional data (2015-2016), which provided observations from each individual in a single social environment, did not provide evidence of this plasticity. Post-hoc analyses revealed that evidence of social plasticity in this system was primarily due to within-individual changes in behaviour, which we were unable to estimate in the cross-sectional data. Our results demonstrate that red squirrels can reduce the costs of territoriality by appropriately adjusting behaviour in response to changes in their social environment. However, our results also suggest that estimating plasticity by comparing behaviour among individuals (i.e. cross-sectional analyses) may not always be reliable. Our ability to detect these effects may therefore depend on having data with multiple observations from the same individuals across different social environments.

animal behavior and cognition↗

bioRxiv2018

ICeD-T Provides Accurate Estimates of Immune Cell Abundance in Tumor Samples by Allowing For Aberrant Gene Expression Patterns

Immunotherapies have achieved phenomenal success in the treatment of cancer and promise even more breakthroughs in the near future. The need to understand the underlying mechanisms of immunotherapies and to develop precision immunotherapy regimens has spurred great interest in characterizing immune cell composition within the tumor microenvironment. Several methods have been developed to estimate immune cell composition using gene expression data from bulk tumor samples. However, these methods are not flexible enough to handle aberrant patterns of gene expression data, e.g., inconsistent cell type-specific gene expression between purified reference samples and this cell type in tumor samples. In this paper, we present a novel statistical model for expression deconvolution called ICeD-T (Immune Cell Deconvolution in Tumor tissues), which models gene expression by a log-normal distribution that is appropriate for both microarray and RNA-seq data. ICeD-T automatically identifies aberrant genes whose expressions are inconsistent with the deconvolution model and down-weights their contributions to cell type abundance estimates. We evaluated the performance of ICeD-T versus existing methods in simulation studies and several real data analyses. ICeD-T displayed comparable or superior performance to these competing methods. Applying these methods to assess the relationship between immunotherapy response and immune cell composition, ICeD-T is able to identify significant associations that are missed by its competitors.

genomics↗

bioRxiv2018

Combinatorial library of biodegradable polyesters enables delivery of plasmid DNA to polarized human RPE monolayers for retinal gene therapy

AbstractEfficient gene delivery into hard-to-transfect cells is still a challenge despite significant progress in the development of various gene delivery tools. Non-viral and synthetic polymeric nanoparticles offer an array of advantages for gene delivery over the viral vectors and high in demand as they are safe to use, easy to synthesize and highly cell-type specific. Here we demonstrate the use of a high-throughput screening (HTS) platform to screen for biodegradable polymeric nanoparticles (NPs) that can transfect human retinal pigment epithelial (RPE) cells with high efficiency and low toxicity. These NPs can deliver plasmid DNA (pDNA) to RPE monolayers more efficiently compared to the commercially available transfection reagents without interfering the global gene expression profile of RPE cells. In this work, we have established an HTS platform and identified synthetic polymers that can be used for high efficacy non-viral gene delivery to human RPE monolayers, enabling gene loss- and gain-of-function studies of cell signaling and developmental pathways. This platform can be used to identify the optimum polymer, weight-to-weight ratio of polymer to DNA, and the dose of NP for various retinal cell types.

bioengineering↗

bioRxiv2017

Mapping Tumor-Specific Expression QTLs In Impure Tumor Samples

The study of gene expression quantitative trait loci (eQTL) is an effective approach to illuminate the functional roles of genetic variants. Computational methods have been developed for eQTL mapping using gene expression data from microarray or RNA-seq technology. Application of these methods for eQTL mapping in tumor tissues is problematic because tumor tissues are composed of both tumor and infiltrating normal cells (e.g. immune cells) and eQTL effects may vary between tumor and infiltrating normal cells. To address this challenge, we have developed a new method for eQTL mapping using RNA-seq data from tumor samples. Our method separately estimates the eQTL effects in tumor and infiltrating normal cells using both total expression and allele-specific expression (ASE). We demonstrate that our method controls type I error rate and has higher power than some alternative approaches. We applied our method to study RNA-seq data from The Cancer Genome Atlas and illustrated the similarities and differences of eQTL effects in tumor and normal cells.

genomics↗