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Type d'Item : Item , A Study of Aegilops Genomes: Towards Understanding Their Evolution and Potential for Wheat Improvement(Université d'Ottawa / University of Ottawa, 2026-08-21) Shazadee, Hamna; Cloutier, Sylvie; You, Frank M.Crop improvement has historically relied on the continuous enhancement of yield, adaptability, and resilience, yet polyploidization, domestication and modern breeding have narrowed the genetic diversity of cultivated wheat. Wild relatives, particularly species within the genus Aegilops, represent a critical reservoir of untapped genetic variation with the potential to address emerging agricultural challenges. Despite their evolutionary and agronomic importance, genomic resources for many Aegilops species have remained limited, restricting comprehensive investigations of their genome evolution and utilization in wheat improvement. In this study, high-quality genome assemblies and gene annotations were generated for 18 diploid, tetraploid, and hexaploid Aegilops species, which, together with previously published genomes, complete a reference set for all 25 species within the genus. Assembly sizes ranged from 5.24 Gb in diploids to 12.65 Gb in polyploids, with high contiguity enabling detailed analyses of complex and repeat-rich genomic regions. Gene annotation provided a comprehensive overview of protein-coding gene content across all assembled Aegilops genomes. The annotated gene sets offer a consistent resource for comparative genomic analyses and functional exploration across the genus. Phylogenetic reconstruction based on near single-copy orthologs across Triticum and Aegilops genomes provided a well-resolved evolutionary framework and confirmed relationships between polyploid genomes and their diploid progenitors. Divergence time estimates further contextualized species evolution within the genus. Comparative analyses of structural variation revealed extensive genome restructuring following polyploidization, including insertions, deletions, duplications, and rearrangements, while maintaining overall syntenic conservation. These patterns highlight the dynamic nature of polyploid genomes and their divergence from ancestral states. Genome-wide characterization of transposable elements revealed that Aegilops genomes are dominated by long terminal repeat (LTR) retrotransposons, with evidence of both conserved and subgenome-specific patterns of expansion and contraction. Temporal analyses of LTR insertions indicated variation in insertion activity over time, reflecting differences in transposable element dynamics among species and subgenomes. Together, these results provide a comprehensive and integrative view of genome evolution in Aegilops, linking genome structure, transposable element dynamics, and evolutionary history across ploidy levels. The genomic resources and insights generated in this study not only advance our understanding of polyploid genome evolution but also provide a valuable foundation for harnessing Aegilops diversity to improve the resilience, adaptability, and productivity of cultivated wheat.Type d'Item : Item , Advances in the Syntheses of Fusarium-Derived Natural Products: Progress Toward Immunomodulide and the Total Synthesis of Fusahexin(Université d'Ottawa / University of Ottawa, 2026-08-21) Natola, Claudia; Boddy, Christopher N.Fungal natural products represent a chemically diverse and pharmacologically rich source of bioactive scaffolds, yet the majority remain incompletely characterized at the level of structure, biosynthesis, and biological function. Across the 12-membered cyclic tridepsipeptide family, to which Fusarium-derived immunomodulide belongs, biochemically characterized biosynthetic gene clusters remain the exception rather than the rule, leaving stereochemical assignment dependent on total synthesis in the absence of reliable biosynthetic prediction. These structural and biosynthetic uncertainties place practical limits on real-world applications for these compounds. The development of immunomodulide as a sustainable plant immune potentiator has been limited by the absence of a validated pharmacophore model and unresolved polyketide stereochemistry, and investigation into fusahexin's proposed role in Fusarium virulence and cell surface hydrophobicity has been limited by the absence of synthetic access to both the natural product and its biosynthetic precursor. This thesis describes the use of total synthesis, comparative spectroscopic analysis, and biosynthetic investigation to resolve these structural and functional gaps for two macrocyclic fungal natural products. We have established the first pharmacophore model for the 12-membered cyclic tridepsipeptide class, identifying the native D-Trp/L-Pip macrolactam configuration as essential for immunomodulide's plant immunopotentiating activity and confirming that this activity translates into reduced bacterial colonization in planta. We have narrowed the stereochemical assignment of immunomodulide's polyketide-derived fragment from sixteen possible permutations to a single synthetic lead using comparative ¹³C NMR analysis, and have advanced its total synthesis to the macrolactamization precursor, providing a foundation for the future development of a lead scaffold for sustainable crop protection. Using a synthesis-supported workflow, CRISPR/Cas9 gene editing and comparative metabolomics, we have identified prefusahexin as the direct biosynthetic precursor to fusahexin and achieved the total syntheses of both natural products, with a reduction-triggered cyclization cascade delivering fusahexin's fused N,O-acetal in high yield. We have further shown that the fusahexin biosynthetic gene cluster is split across the genome and, through biomimetic oxidation of prefusahexin, implicated copper amine oxidases as the enzyme class responsible for the key oxidative transformation linking the two natural products. The synthetic and biosynthetic platforms presented in this thesis will be fundamental to pursuing further biological and translational investigations of these fungal natural products.Type d'Item : Item , Trends in Cardiovascular-Kidney-Metabolic Risk Factors and Diseases and in Ontarian Adolescents and Young Adults, 2006-2023: A Population-Based Cohort Study(Université d'Ottawa / University of Ottawa, 2026-08-21) Islam, Raidah; Sood, Manish M.Background: Evidence suggests that the burden of cardio-kidney-metabolic (CKM) disease is shifting to younger populations. The objective of this thesis is to analyze recent trends in various CKM risk factors and disease outcomes in young Ontarians over the past two decades. Methods: A retrospective population-based cohort study of Ontarians aged 13-40 years old was conducted using ICES data. Results: Incidence of CKM outcomes such as diabetes, congestive heart failure, and arrythmia all significantly increased from 2006-2009 to 2020-2023 (IRRs 1.23-1.79, 95% CIs 1.17-1.93), while hyperlipidemia and coronary artery disease decreased (IRRs 0.54-0.75, 95% CIs 0.50-0.78). CKM trends also varied across different age strata, with 13-18 year olds seeing the largest annual percent increases in several critical outcomes. Conclusions: Increases in key CKM risk factors and diseases have occurred in Ontario's younger population from 2006-2023. Future health strategies should focus on disease prevention in this population.Type d'Item : Item , De Novo Enzyme Design by Customizing Minimal TIM Barrels(Université d'Ottawa / University of Ottawa, 2026-08-21) Smith, Benjamin; Chica, Roberto A.Enzymes are the most efficient and selective catalysts known, and the ability to design an enzyme for a target reaction is a primary goal of protein engineering. Among natural enzymes, the TIM barrel represents the most prevalent and versatile protein fold, using extended loops and other structural elements to facilitate substrate binding, catalysis, and product release. While de novo TIM barrels have been successfully designed, their minimalistic architectures lack these essential structural elements. In this work, we present CANVAS, a computational framework for de novo enzyme design that introduces a structural lid into a minimal de novo TIM barrel to anchor catalytic residues and form an active-site pocket. To evaluate this workflow, we design TIM barrel enzymes with active sites for the Kemp elimination reaction. Four out of nine designs showed measurable activity, with the most active reaching a catalytic efficiency of 21,000 M⁻¹ s⁻¹ at pH 10. Crystal structures of this variant bound to a transition-state analogue confirmed the accuracy of the designed lid and identified a shift in the designed lid between bound and unbound forms, reminiscent of rearrangements in natural TIM-barrel enzymes. Using the X-ray structure of a lower-activity variant (19 M⁻¹ s⁻¹), we applied ensemble-based design to optimize its active site, increasing catalytic efficiency to 32,000 M⁻¹ s⁻¹. This optimized enzyme also demonstrated high regioselective preference for the target substrate. These results demonstrate that de novo TIM barrels can be customized with bespoke substrate binding pockets supporting efficient catalysis, establishing a platform for building de novo enzymes from minimal protein scaffolds. We propose strategies to push catalytic efficiency further by expanding CANVAS and combining it with complementary approaches, and we describe the next frontiers for de novo enzyme design.Type d'Item : Item , Plato's Criticism of Socrates(Université d'Ottawa / University of Ottawa, 2026-08-21) Cayer, Fabien; Gonzalez, Francisco J.This dissertation concerns the practical and methodological difference between Plato and his Socrates. Whereas Socrates pursues wisdom in oral conversation, directly and publicly examining, questioning, refuting, and reproaching his fellow Athenians, Plato creates wisdom by writing dramatic dialogues chiefly featuring Socrates. Typical explanations of this difference turn on the comparative effectiveness of written texts for Plato's philosophical and political aims, but these explanations have not yet adequately explored the ways in which Socrates' oral dialectic is ineffective. The purpose of this dissertation, then, is to explore the ineffectiveness of Socrates' oral dialectic. I do this by focusing on four dialogues in which Plato represents Socrates' interlocutor making an explicit critique of Socrates: the Apology, the Clitophon, the Euthydemus, and the Gorgias. These four critiques are related but not identical, occurring each in its own dramatic context and emphasising distinct aspects of Socrates' occupation. As such, I analyse and evaluate each critique individually. In general, I show that Socrates' critics mistake and misunderstand certain details of Socrates and his occupation, but are nevertheless on the right track with their critique. In Chapter 1, I show that Socrates' accusers are wrong to charge Socrates with impiety for the reasons that they do but that Socrates' defence speech itself nevertheless vindicates their accusations, demonstrating before the judges and Plato's readers that his occupation does in fact imply his guilt. Next, in Chapter 2, I show that Clitophon wrongly expects Socrates to resolve his aporia and teach him justice following his apparently protreptic speech because he is in fact ignorant of justice but that Socrates' ignorance belies his responsibility for Clitophon's aporia and so for his continued injustice. In Chapter 3, I show that Socrates' anonymous critic at the end of the Euthydemus rightly critiques Socrates for willingly submitting to Euthydemus and Dionysodorus in his conversation with them, and as such for risking the quality of Clinias's soul. Finally, in Chapter 4, I show that Callicles, despite wrongly promoting the tyrannical life of rhetoric, nevertheless rightly critiques Socrates for his inexperience with respect to human affairs and so his powerlessness in actually creating justice. I conclude by reflecting on the significance of these critiques for the difference between Plato and his Socrates: not that Plato's written dialectic is more effective but that it is safer. -- Cette dissertation parle de la différence pratique et méthodologique entre Platon et son Socrate. Tandis que Socrate poursuit la sagesse par la conversation orale, en examinant, questionnant, réfutant et réprimandant publiquement et directement ses camarades Athéniens, Platon crée la sagesse en écrivant des dialogues dramatiques mettant principalement en scène Socrate. Les explications habituelles de cette différence s'appuient sur l'efficacité comparée des textes écrits pour atteindre les objectifs philosophiques et politiques de Platon, mais elles n'ont pas encore suffisamment exploré les raisons de l'inefficacité de la dialectique orale de Socrate. L'objectif de cette dissertation est donc d'explorer cette inefficacité. Pour ce faire, je me concentre sur quatre dialogues dans lesquels Platon présente l'interlocuteur de Socrate formulant une critique explicite de ce dernier: l'Apologie, le Clitophon, l'Euthydème et le Gorgias. Ces quatre critiques sont connectés mais non identiques, chacune s'inscrivant dans un contexte dramatique spécifique et mettant l'accent sur des aspects distincts de l'activité de Socrate. Par conséquent, j'analyse et évalue chaque critique individuellement. En général, je démontre que les critiques de Socrate commettent des erreurs et interprètent mal certains détails concernant Socrate et sa profession, mais que leur critique reste néanmoins pertinente. Au Chapitre 1, je montre que les accusateurs de Socrate ont tort de l'accuser d'impiété pour les raisons invoquées, mais que son discours de défense, à lui seul, justifie leurs accusations, démontrant aux juges et aux lecteurs de Platon que sa profession implique bel et bien sa culpabilité. Ensuite, au Chapitre 2, je montre que Clitophon attend à tort de Socrate qu'il résolve son aporie et lui enseigne la justice après son discours apparemment protreptique, car il ignore en réalité la notion de justice. Mais cette ignorance révèle la responsabilité de Socrate dans l'aporie de Clitophon et, par conséquent, dans l'injustice qu'il perpétue. Au Chapitre 3, je démontre que le critique anonyme de Socrate à la fin de l'Euthydème le critique à juste titre pour s'être soumis volontairement à Euthydème et à Dionysodore lors de leur conversation, mettant ainsi en péril l'âme de Clinias. Enfin, au Chapitre 4, je montre que Calliclès, malgré sa promotion erronée d'une vie rhétorique tyrannique, critique néanmoins avec justesse Socrate pour son inexpérience des affaires humaines et, par conséquent, son impuissance à instaurer une véritable justice. Je conclus en réfléchissant à la portée de ces critiques quant à la différence entre Platon et son Socrate: non pas que la dialectique écrite de Platon soit plus efficace, mais qu'elle soit plus sûre.