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Recherche uO, le dépôt numérique de l'Université d'Ottawa, réunit le matériel de recherche et d'enseignement créé par notre communauté universitaire et nos partenaires. Le savoir de l'Université est ainsi disponible à long terme et en accès libre, ce qui lui procure de la visibilité et facilite sa diffusion.

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A Holistic Assessment of Trace Metal Mobility Near Abandoned Mine Sites in the Wheaton River Watershed, Yukon, Canada
(Université d'Ottawa / University of Ottawa, 2026-09-23) Rorabeck, Katelyn; St. Pierre, Kyra
The Wheaton River Watershed, located in southern Yukon, feeds Bennett Lake and ultimately the Yukon River, and has been heavily impacted by recreation and mining activities dating back to the Klondike Gold Rush (1896). This watershed is within the Traditional Territory of the Carcross/Tagish First Nation (C/TFN), who have stewarded these lands since time immemorial, and hold concerns over impacts of point source contamination on broader ecosystem health. Despite the common understanding of ecosystem connectivity among locals, assessments of trace metal mobility across multiple environmental media are overlooked when approaching research using perspectives exclusively rooted in Western Science. Despite this knowledge, no assessment of trace metal mobility has been conducted in the watershed, leaving questions surrounding the extent of contaminant point source impacts on the catchment as a whole largely unanswered. Co-created with C/TFN staff and community members, this thesis took a holistic approach to assess the current distribution and potential for trace metal mobility on a watershed scale. Water, plant, scat and sediment samples collected at mine-impacted and downstream sites were analyzed for trace metals, focusing on those posing known risks to human and animal health (As, Cd, Hg, Pb, and Sb) to investigate the extent of metal mobility between media and throughout the catchment, supported by sequential extraction and stable isotope analyses. There were both region and metal-specific patterns of trace metal distribution and mobility, with most trace metals stored in sediments at mine-impacted sites. Metals in water samples followed similar trends to solid samples; however, lower concentrations, especially in the mainstem Wheaton River relative to mine-impacted samples, suggested either or both low mobility and dilution from other water sources as driving factors at this time. Flux analyses and yield calculations indicated that the cumulative Wheaton River trace metal exports into Bennett Lake were comparable or below western Arctic references. This thesis explores trends of multi-media metal mobility from mine-impacted sites on a watershed scale, informed by perspectives rooted in Western Science and Indigenous knowledge, highlighting the complex, connected, and dynamic nature of the watershed. Findings from this thesis will help inform land planning and stewardship initiatives led by C/TFN, remediation efforts, and guide future research in the region.
Solving Undiagnosed Neuromuscular Disorders: Uncovering Causative Genotypes Beyond Known Genes and Beyond the Exome
(Université d'Ottawa / University of Ottawa, 2026-09-23) Sivasankar, Malaichamy; Lochmüller, Hanns
Neuromuscular disorders (NMDs) are a group of inherited diseases that are highly heterogeneous both clinically and genetically. The global prevalence is approximately 1 in 1,000. To date, ~700 genes have been identified to be associated with NMDs. The genetic cause of inherited NMDs in many families remains elusive even after extensive investigation, indicating the possibility of novel genes and genetic mechanisms that have yet to be explored. In addition, lack of a definitive diagnosis can interfere with disease prognosis, classification, and therapeutic options. This thesis aimed to identify the genetic cause of unsolved NMD cases by combining systematic genomic reanalysis with detailed phenotype assessment and functional studies. This would provide patients with a confirmed diagnosis, improved disease management, and access to therapy or inclusion in therapeutic trials. As part of this work, pre-existing NGS datasets from 101 previously unsolved NMD families were systematically reanalysed using updated bioinformatic approaches and phenotype-driven variant prioritization strategies. This led to a diagnostic yield of 16.83%, with causative variants identified in 17 families. In five cases, intronic variants in known NMD genes (COL6A3, SGCA, DOK7, DYSF, CHRND) were considered causative following in silico predictions and careful correlation with the phenotype. One case had an extended phenotype (PTPN11), and one case had a dual diagnosis (MYH2, KIF21A). A novel ATP2A2 missense variant was identified in two unrelated families, establishing ATP2A2 as a new NMD gene. This thesis also identified and characterized a distinct pathogenic mechanism underlying congenital myasthenic syndrome (CMS) caused by variants in the intracellular M3-M4 cytoplasmic loops of acetylcholine receptor (AChR) subunits encoded by CHRND and CHRNA1. Unlike classical AChR-related CMS, these variants showed preserved surface expression and largely normal channel kinetics in conventional functional assays. However, agrin-induced clustering assays in genetically modified C2C12 myotubes demonstrated markedly impaired AChR clustering, establishing defective postsynaptic receptor aggregation as the primary disease mechanism. In addition, this work established a novel association between a heterozygous ATP2A2 missense variant and dominantly inherited recurrent rhabdomyolysis. Functional studies showed impaired SERCA2-mediated calcium reuptake and abnormal intracellular calcium homeostasis in skeletal muscle, supporting the pathogenicity of the identified variant. Overall, this thesis showed that research-based reanalysis of pre-existing NGS data improved the diagnostic yield of previously unsolved cases consistent with previous literature, reinforcing the utility of in-depth, phenotype-driven reanalysis with expert review. The findings highlight the evolving nature of genomic reanalysis and interpretation, demonstrating that previously unsolved cases may become diagnosable as our knowledge of disease genes, variant interpretation and analytical tools continues to improve.
Human-Centered Urban Intelligence through Context-Aware Recommendation Using IoT and Digital Twins
(Université d'Ottawa / University of Ottawa, 2026-09-23) Alharthi, Saeed; El-Saddik, Abdulmotaleb
Rapid urbanization has increased the need for intelligent urban systems that can support context-sensitive decisions for individuals operating under changing environmental and infrastructural conditions. This thesis addresses the lack of an integrated operational framework that connects Internet of Things sensing, artificial intelligence, and Digital Twin representations for personalized services in smart urban environments. The research is motivated by the fragmentation of existing smart-city systems, in which sensing, analytics, recommendation, and simulation are often developed as separate components and are commonly evaluated mainly through accuracy-oriented metrics. To address this gap, the thesis proposes a unified framework that combines IoT-based context acquisition, structured context modeling, context-aware predictive and recommender models, and interoperable Digital Twins of users, points of interest, and urban environments. The framework transforms heterogeneous urban data into multi-dimensional contextual representations spanning environmental, spatial, temporal, and activity-related factors. It employs a hybrid wide-and-deep learning architecture to support prediction and recommendation under dynamic conditions. Within the proposed pipeline, Digital Twins extend recommendations beyond immediate ranking by enabling simulation-based reasoning over alternative actions and their anticipated consequences. The evaluation combines offline model assessment with scenario-based and productivity-oriented analysis. Under the reported evaluation setting, the proposed context-aware wide-and-deep model achieved the strongest predictive performance among the evaluated models, attaining an RMSE of 0.3695 and explaining approximately 81.9% of the variance in observed preference scores. Compared with matrix factorization, neural collaborative filtering, and collaborative filtering baselines, the proposed model reduced prediction error and captured contextual variation more effectively. The broader system-level analysis further indicates that contextual recommendation and Digital Twin-based reasoning can support recommendation relevance, activity planning, decision interpretation, and alignment between user goals and available urban resources. The thesis also identifies important constraints related to data quality, sensing coverage, privacy, scalability, and transferability across urban contexts. Overall, the work shows that personalization in smart cities can be framed and assessed as an integrated, human-centered decision-support problem rather than as an isolated recommendation task.
The Evolutionary Consequences of Mate Competition: Adaptation, Purging and Sexual Conflict in Drosophila melanogaster
(Université d'Ottawa / University of Ottawa, 2026-09-23) Osijo, Adeyanju; Rundle, Howard D.
Mate competition is a widespread feature of sexual reproduction that can have diverse evolutionary consequences. By generating sexual selection, competition for mates can favour healthier and more vigorous males, potentially promoting adaptation and the purging of deleterious alleles. However, traits that increase male reproductive success can also reduce female fitness as a by-product, generating sexual conflict and male-imposed harm. These evolutionary consequences are not fixed because both the potential benefits and costs of mate competition may vary depending on how mating interactions unfold, the environment in which they occur, and the evolutionary history of the populations involved. Drosophila has been a model system for studying sexual selection, sexual conflict, and male harm. Much of this work has been conducted using laboratory-adapted populations maintained and assayed in highly simplified environments. Because both sexual selection and male harm can influence adaptation, purging, and population fitness, environmental effects on mate competition can have broad evolutionary consequences. Yet we know relatively little about how mating environments alter the strength of selection and the expression of male harm, or how these effects should influence our interpretation of past work. In this thesis, I examined how the physical mating environment and population evolutionary history shape selection through males and the expression of male harm in Drosophila. In my first experiment (Chapter 2 of this thesis), I tested whether selection through D. melanogaster males was stronger in a larger, structurally complex mating environment than in smaller, structurally simple environment (standard Drosophila vials) by comparing the fitness of inbred and outbred flies. Selection against inbred males was strong, but the evidence that this selection was stronger in complex environments was inconclusive: one experiment showed an effect in this direction that approached, but did not achieve, statistical significance, whereas a second experiment found no difference between environments. In my second experiment (Chapter 3), I examined which features of the mating environment reduce the expression of male harm in D. melanogaster. By separately manipulating fly density and structural complexity, I showed that structural complexity alone, and not density, reduced the expression of male harm; indeed, harm was essentially eliminated in the structurally complex treatment. In my third experiment (Chapter 4), I investigated whether male harm differed between lab-adapted and nature-derived populations in two species of Drosophila. Across three comparisons, lab-adapted males generally imposed greater fitness costs on females than did nature-derived males. This suggests that long-term adaptation to simplified laboratory environments may increase the expression of male harm, although the strength of this effect sometimes depended on species and male-female population combination. Taken together, my results show that the evolutionary consequences of mate competition can be context-dependent because both the physical environment and a population's evolutionary history can shape selection and sexual conflict. Mate competition may contribute to adaptation and purging, but it can also generate male harm, and the balance between these outcomes depends on the conditions under which mating occurs and the populations involved. Standard Drosophila laboratory assays may also overestimate the magnitude of male harm, particularly when they use long-term lab populations in structurally simple environments. A fuller understanding of sexual selection and sexual conflict will therefore require greater attention to mating environment, population history, and the extent to which laboratory findings reflect processes occurring in more natural contexts.
Development of Collagen-Like Peptide Hydrogel Biomaterials for Soft Tissue Repair
(Université d'Ottawa / University of Ottawa, 2026-09-22) Ross, Alex; Alarcon, Emilio I.; Suuronen, Erik J.
Unmet needs in soft tissue repair, such as chronic wounds, scarring, corneal blindness, and heart failure, urgently require new therapies. Hydrogel soft biomaterials offer a promising solution. While traditionally classified as polymers from natural or synthetic sources, advancements in chemical synthesis now enable the synthetic production of natural biofunctional molecules like peptides and proteins. Thus, bioinspired synthetic hydrogels can be designed as reliable, cost-effective and pathogen-free alternatives for soft tissue repair. Synthetic collagen-like peptides (CLPs) can form natural tissue structures and self-assemble into triple-helix trimers to create 3D hydrogels. In this doctoral dissertation, I developed CLP materials using supramolecular self-assembly and either spontaneous thiol-maleimide Michael addition or photoactivated radical thiol-ene reactivity. A low-volume, rapid combinatory screening approach identified ideal candidates from a library of synthetic peptides. Adjusting peptide concentration or structural properties like junction functionality and reactive group choice allows for hydrogel tuning. Ex vivo, in vitro, and in vivo assays assessed the materials' soft tissue repair capabilities. Collagenase degradation and live/dead assays showed suitable biocompatibility and biodegradability. Peptide hydrogels sealed corneal perforations or altered corneal shape. Skin adhesion tests showed strong wound closure strength comparable to commercial adhesives. In vivo wound treatment accelerated healing while reducing epithelial thickness and increasing collagen content. In a mouse model of myocardial infarction, CLP hydrogel-treated hearts preserved function at 28 days, while saline control lost function. These results suggest that peptide-based hydrogels are a promising platform for soft tissue repair of the skin, cornea, and heart.