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The impact of a delayed SARS-CoV-2 vaccine dose interval on the immune system: B cell maturation and antibody neutralization
No full textEarly in the COVID-19 vaccine rollout, Canada implemented a dose-sparing strategy by delaying second doses to increase first-dose coverage. A longer interval between doses was associated with improved antibody titres and inhibition of variants. These improvements may reflect enhanced B cell affinity maturation during the extended interval. This study examines the effects of an extended dose interval on B cell maturation after the primary dose series and following a booster dose in mRNA vaccine recipients from Manitoba.
Blood samples were collected at multiple timepoints from participants who received either a short or extended dose interval. Peripheral blood mononuclear cells were isolated and stained with fluorescent probes to detect and phenotype antigen-specific B cells over time using flow cytometry. A delayed dose interval led to a greater increase in Spike-specific and RBD-specific B cells and antigen-specific memory B cells 1-2 weeks after the second dose compared to a standard dose interval. Spike-specific and RBD-specific B cells in the standard dose interval participants increased to match the levels in the delayed dose interval participants 6 months after the second dose. The impact of a third dose in both groups did not result in differences in the proportions of SARS-CoV-2-specific B cells between participants with standard or extended dose intervals.
To investigate the impact of dose interval on antibody maturation over time, PBMCs from various post-vaccination timepoints were stimulated in vitro to differentiate memory B cells into antibody-secreting plasma cells. Antibodies derived from antibody-secreting plasma cells in participants with a delayed dose interval saw increased affinity and a wider breadth of inhibition for SARS-CoV-2 RBD 10-14 days following the second dose of the vaccine compared to standard dose interval participants. The third dose did not result in differences in the breadth of inhibition between participants with standard or extended dose intervals.
Dosing intervals affect B cell phenotypic proportions and antibody responses following vaccination. Extended intervals transiently increase SARS-CoV-2-specific B cell frequencies and antibody breadth, suggesting greater maturation, but shorter intervals eventually yield comparable responses. The study will shed light on whether the establishment of long-term memory B cells is also affected, with implications for future vaccine strategies.October 202
Consequences of genital inflammation and potentialstrategies for its regulation by inducing regulatory T cells
No full textHIV remains a global health threat, disproportionately affecting adolescent girls and young women in sub-Saharan Africa. One factor linked to increased HIV acquisition risk is genital inflammation, defined by elevated levels of pro-inflammatory cytokines and chemokines in cervicovaginal secretions. Excessive genital inflammation reduces the efficacy of tenofovir gel, disrupts the mucosal barrier, and recruits HIV target cells. Thus, regulating genital inflammation could help reduce HIV risk among women.
We previously found that endocervical Tregs inversely correlated with genital inflammation and HIV target cell abundance in the female genital tract (FGT), hence, we hypothesized that inducing Tregs in the FGT could help regulate genital inflammation. IL-2 is known to induce Tregs, and efforts are underway to enhance its regulatory activities. In this thesis, using a mouse model, we showed that intraperitoneal administration of trimeric IL-2 conjugates (IL-2C) in estrous-synchronized FoxP3GFP female mice significantly increased the frequency and count of CD4+GFP+Tregs or CD25+CD127loTregs in the lower FGT, and this was confirmed by immunofluorescence analyses. Again, IL-2C increased GITR expression on Tregs but had minimal impact on non-Treg cells such as NK1.1+ NK cells, CCR6+ Th17, CD8+CXCR3+ and CD4+CXCR3+ T cells. We also observed that trimeric IL-2C pre-treatment prevented neutrophil influx during vaginal challenge with Nonoxynol-9 (N-9) and Mobiluncus mulieris. However, maintenance of E-cadherin expression and barrier integrity was observed only with M. mulieris and depletion of FoxP3+Tregs reversed the protective effects of IL-2C.
Most human studies have focused on alterations of the immune milieu from cytobrushes and mucosal secretions, without investigating the changes occurring within the genital tissues themselves. Therefore, in this thesis, we used immunofluorescence and spatial transcriptomics analyses to study the impact of genital inflammation on barrier integrity and target cell frequencies in ectocervical tissues from female sex workers in Nairobi. CD4+T and Th17 cell counts correlated with IP-10 levels (p<0.05). Spatial transcriptomics revealed mucosal barrier disruption, with reduced expression of genes for E-cadherin (CDH1), keratins (KRT), desmoglein/desmocollin (DSG3, DSC1), and claudin (CLDN1).
In conclusion, this thesis identifies a strategy for inducing genital Tregs to regulate inflammation and preserve barrier integrity, potentially reducing HIV risk and improving reproductive health outcomes among women.October 202
Changing perspective: a new approach to adolescent mental health care
No full textThis practicum will address the growing need for adolescent mental health services in Winnipeg. This project will proactively approach mental health, offering support groups and classes that promote social interaction among users and education on the stigma surrounding mental illness. The centre will host counseling and educational workshops for adolescents ranging from age 12 - 20, struggling with depression and anxiety.
From art classes to physical activities, the centre will offer unique therapeutic approaches to address users’ specific needs. Poor mental health often harms adolescents’ education, relationships, and social skills if not treated. Without proper care and support mental illness can lead to higher numbers of youth struggling with social anxiety, homelessness, and suicidal thoughts. The purpose of this centre will be to enhance the discussion around mental health and continue to educate on the importance of mental care. The centre will provide a community for individuals dealing with depression and anxiety, a space where adolescents can find comfort and support. An accessible mental health service such as this centre is essential to begin addressing this issue and removing the stigma surrounding it. Interior design will be utilized as a mediator, providing a sense of connection and belonging for all, to simplify the user experience.October 202
Selling order matters in sequential auctions: experimental evidence
No full textWe study how the order in which two heterogeneous products are sold in a second-price sequential auction affects efficiency, revenue, and, notably, the probability of ex-post loss for bidders. Theoretically, when the lower variance product is sold first, rather than second, the probability of ex-post loss for the global bidder increases. This leads to higher revenue at the expense of bidders, while reducing efficiency. Our experimental results confirm this theoretical prediction, showing that the probability of ex-post loss is indeed higher when the lower variance product is sold first, and that efficiency increases under this ordering when synergy is low. This risk of ex-post loss is important because if firms go bankrupt due to overbidding, they may fail to complete critical public projects such as highways or hospitals, causing delays that prevent the public from accessing essential services. Our study shows the correct selling order to mitigate this problem, offering insights that can help shape public policy to minimize bidder losses and improve project completion outcomes.October 202
Swipe your stress away: does social media use buffer young adults from acute stress?
No full textEmerging adulthood is a critical developmental stage often characterized by heightened exposure to acute and chronic stressors, which are associated with increased mental health challenges and emotional vulnerability (Clayborne et al., 2019; Floriou-Servou et al., 2021; MacLeod & Brownlie, 2014). Social media is frequently used by young adults as a stress coping strategy (Bae, 2023; O’Reilly, 2020), and theories suggests it may offer both social buffering and distraction during stress recovery (Gunnar, 2017; Mansell et al., 2020). The present study examined whether brief social media use facilitates recovery from an acute stressor in young adults and whether this effect is moderated by ADHD symptomology. Individuals with ADHD symptomology may perceive stress as more intense and difficult to manage (Barra et al., 2021; Combs et al., 2015). Additionally, exploratory multiple regressions within the social media use condition evaluated whether content‐theme predictors, controlling for age, anticipate subjective (VAS) and physiological (PPG) recovery, based on evidence linking high-arousal content to stress and emerging research on social media’s mental health effects (Bucci et al., 2019; Competiello et al., 2023; Naslund et al., 2020; Zhao & Zhou, 2020). Given social media’s prevalence in the daily lives of young people, it was hypothesized that it may serve as an accessible coping strategy. Participants from the University of Manitoba were sampled and completed an online version of the Trier Social Stress Test (TSST), followed by random assignment to either a 5-minute social media use condition (n = 49) or a control condition (n = 53). Stress recovery was assessed using both subjective (visual analog scale) and physiological (heart rate) measures at multiple time points. The findings demonstrated that social media use did not significantly improve stress recovery relative to the control and ADHD symptomology did not moderate this effect. However, gender identity was a significant factor; women reported higher emotional reactivity across stress and anxiety measures. Although most participants enjoyed using social media, this did not translate to improved recovery outcomes. The results highlight the need to more thoroughly examine content type, quality of engagement, and individual differences when assessing the effectiveness of digital interventions for stress.Arts Graduate Award (value 1,000 used)
Psychology Graduate Fellowship ($15,000)October 202
Host RNA biomarkers of tuberculosis disease and with people living with HIV
No full textTuberculosis remains a leading global health challenge, with early and accurate diagnosis critical for effective disease management. Transcriptomic studies have identified host blood RNA biomarkers as promising diagnostic tools, yet challenges remain in standardizing methodologies and ensuring diverse population representation. Tuberculosis in people living with HIV (PLHIV) presents unique immunological interactions that require further investigation.
This master’s thesis project aimed to synthesize existing transcriptomic research on tuberculosis biomarkers through a scoping review and conduct a primary transcriptomic analysis to identify differentially expressed genes associated with tuberculosis in PLHIV.
A PRISMA scoping review was conducted to evaluate published transcriptomic studies from 2000 to 2024, focusing on host blood biomarkers identified using microarray and RNA sequencing technologies. Furthermore, a primary transcriptomic analysis was performed using whole-blood and PBMC samples from 96 participants across four cohorts: tuberculosis in PLHIV (n=29), tuberculosis alone (n=31), HIV alone (n=23), and non-infected individuals (n=13). Differential gene expression analysis was conducted using DESeq2, with batch effects controlled using ComBat-Seq. Candidate biomarkers were identified by comparing differentially expressed genes with those frequently reported in the scoping review.
The scoping review identified 60 tuberculosis gene signatures comprising 1,939 unique genes, with 15 genes appearing in at least 10 signatures. Microarray remained the dominant methodology; however, RNA sequencing datasets have increased in recent years. The primary study identified 10,308 differentially expressed genes, with six—GBP6, DHRS9, GBP5, CD274, FCGR1A, and ANKRD22—frequently appearing in tuberculosis gene signatures and showing significant upregulation in tuberculosis in PLHIV. These genes are linked to immune activation, inflammatory responses, and antigen processing, highlighting their potential as tuberculosis biomarkers.
This master’s thesis project highlights the potential of transcriptomic biomarkers for tuberculosis diagnosis, particularly in PLHIV, while highlighting critical areas for future research. Expanding cohort recruitment in high tuberculosis burden countries such as India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and the Democratic Republic of the Congo will be essential to enhance the generalizability of identified biomarkers. Additionally, considering tuberculosis as a disease spectrum—including incipient, minimal, and subclinical tuberculosis—will be crucial for refining diagnostic applications.October 202
When is a Pyridine Not a Pyridine? Benzannulated N-Heterocyclic Ligands in Molecular Materials Chemistry
No full textThe C=N bond is a critical structural piece of many N-donor ligand scaffolds and is central to the properties and reactivity of important coordination complexes. For example, C=N units play a key role in the ‘redox non-innocence’ of α-diimine complexes and in making charge-transfer excited-state character available to complexes of N-heterocyclic ligands such as bipyridine. In N-heterocycles like pyridine, benzannulation can be used to extend the conjugated C=N containing π-system to quinoline (2,3-benzopyridine) to acridine (2,3-benzoquinoline). This stabilizes the lowest unoccupied molecular orbital (LUMO) of the molecule and boosts its electron-accepting properties, but the position of the benzannulation matters. For example, phenanthridine (3,4-benzoquinoline), an asymmetric isomer of acridine, bears a similarly electronically accessible extended π-system but with a more chemically isolated ‘imine-like’ C=N moiety. This Award Paper presents an overview of our work investigating the impact of such site-selective benzannulation on the chemistry and properties of phenanthridine as a molecule and ligand
Photoactive Monofunctional Platinum(II) Anticancer Complexes of Multidentate Phenanthridine-Containing Ligands: Photocytotoxicity and Evidence for Interaction with DNA
No full textPt(II) complexes supported by chelating, multidentate ligands containing π-extended, planar phenanthridine (benzo[c]quinoline) donors (RLPtCl) exhibit a promising in vitro therapeutic index compared with phenanthriplatin, a leading preclinical anticancer complex containing a monodentate phenanthridine ligand. Here, we report evidence for non-specific interactions of CF3LPtCl with DNA through intercalation-mediated turn-on luminescence in O2 saturated aqueous buffer. Brief irradiation with visible light (490 nm) was also found to drastically increase the activity of CF3LPtCl, with photocytotoxicity increased up to 87% against a variety of human cancer cell lines. Mechanistic studies highlight significantly improved cellular uptake of CF3LPtCl compared with cisplatin, with localization in the nucleus and mitochondria triggering effective apoptosis. Photosensitization experiments with 1,3-diphenylisobenzofuran demonstrate CF3LPtCl efficiently mediates the generation of singlet dioxygen (1O2), highlighting the potential of RLPtCl in photodynamic therapy
Identification of bioplastic degradation abilities and associated genes in Burkholderia with synthetic biology tools
No full textThe Burkholderia genus exhibits a dual nature; while some species are opportunistic pathogens, others hold immense biotechnological potential due to their vast metabolic capacity. Harnessing the beneficial traits of Burkholderia while mitigating risks would require genetic tools to elucidate gene-to-function relationships and enable genetic manipulation. This thesis focuses on developing and utilizing genetic tools for Burkholderia and applying them to study bioplastic degradation, specifically medium-chain-length polyhydroxyalkanoates (mcl-PHA).
To address some of the limitations in existing genetic tools, a CRISPR-associated transposase system, RhaCAST, was developed as a targeted DNA insertion platform for Burkholderia. RhaCAST enables loss- and gain-of-function applications and allows for iterative genetic manipulations by excising and reusing selection markers. The system was applied to three species, B. cenocepacia K56-2, B. multivorans ATCC 17616, and B. vietnamiensis LMG 16232, demonstrating its versatility across different Burkholderia strains. RhaCAST increases the genetic toolkit available for studying non-model bacteria.
Building on this genetic tool development, the extracellular mcl-PHA degradation capacities of various Burkholderia strains were explored. Screening revealed that strains such as B. gladioli, B. multivorans, and B. vietnamiensis could degrade mcl-PHA, highlighting the genus’s diverse metabolic potential. In order to elucidate the genetic basis of this activity, transposon mutagenesis coupled with Tn-seq analysis was performed on B. vietnamiensis LMG 16232. This analysis identified genetic elements involved in mcl-PHA degradation, including lipase and chaperone genes, type II secretion system components, and regulatory elements such as transcriptional activators and repressors of PHA synthesis. Further validation of mutants generated with RhaCAST confirmed the involvement of these genes in the extracellular mcl-PHA degradation activity, highlighting the role of lipases as enzymes with substrate ambiguity.
Overall, this thesis demonstrates how the development of genetic tools can drive functional genomics studies in non-model bacteria such as Burkholderia. RhaCAST's versatility extends beyond bioplastic degradation, allowing its use in various biotechnological fields, including metabolic engineering and pathogenicity studies. The insights gained into extracellular mcl-PHA degradation mechanisms provide opportunities for enzyme engineering and industrial applications in bioplastic waste management, paving the way for sustainable biotechnology innovation.October 202
Mapping grassland distribution and aboveground biomass in Manitoba’s Prairie Ecozone using multisensor satellite images
No full textGrasslands are one of the most widespread and endangered ecosystems, offering essential services such as food supply, carbon sequestration, soil fertility, biodiversity conservation, water and soil retention, and cultural benefits. Grasslands in the Canadian Prairies have been increasingly degraded by human interventions, leading to native species loss, environmental issues, and biodiversity decline. Therefore, monitoring grassland distribution and biophysical characteristics, like aboveground biomass (AGB), is vital for assessing ecosystem health and supporting sustainable land management. The main goals of this study were (1) to differentiate grasslands into native, tame, and mixed classes using a novel artificial intelligence approach, and (2) to estimate grassland AGB in Manitoba’s Prairie region using diverse remote sensing datasets. For grassland mapping, three advanced machine learning (ML) algorithms—random forest (RF), gradient tree boosting (GTB), and support vector machine (SVM)—were evaluated with input variables derived from Landsat 8-9, Sentinel-1 (S1), Sentinel-2 (S2), and Shuttle Radar Topography Mission (SRTM) data. Finding an optimal data combination (S1 + S2) and using multi-temporal imagery were key components of satellite data processing to improve grassland classification accuracy. Approximately 1,430 optical and radar images and 3,000 grassland samples were used to map grassland classes across Manitoba Prairie Ecozone. RF and GTB achieved the highest performance, with an overall accuracy of around 72%. The impact of multisensor image fusion on grassland classification accuracy was also assessed when multi-temporal data composition was not feasible. For the second objective, both parametric regressions (linear and exponential) and ML methods—RF, support vector regression (SVR), and artificial neural networks (ANN)—were applied to predict grassland AGB. Incorporating environmental variables such as temperature, precipitation, and elevation significantly enhanced model performance. Spectral data from PlanetScope (3 m), Sentinel-2 (10 m), and Landsat 8–9 (30 m) were used as inputs to evaluate sensor performance in biomass estimation. Model training and validation was based on newly derived biomass samples from daily Planet’s Biomass Proxy products, which captured AGB dynamics at 10 m resolution across multiple growing seasons. Results showed that parametric models (R²=0.63–0.65) underperformed compared to ML methods (R²=0.78–0.90).the Canadian Forage and Grassland Association (CFGA)October 202