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    Development of Hybrid Non-Enveloped Viral Vectors Using the Bacterial Miniphagemid Platform
    (University of Waterloo, 2026-01-30) Hosseinali, Mehraveh
    Gene therapy holds significant promise for treating various diseases, with Adeno-associated virus (AAV) vectors being among the most widely used delivery systems. However, current standard AAV production methods relying on costly and inefficient mammalian cell culture limit scalability and clinical accessibility. A similar human virus, Torque teno virus (TTV), also holds great potential for gene therapy; however, it also suffers from problems in its production. To address this manufacturing bottleneck, this study aimed to develop a novel, cost-effective platform for hybrid viral vector production entirely within Escherichia coli. This work advances research on the use of miniphagemids, phages that package a minimal vector genome, to achieve in-bacterial assembly of novel hybrid AAV serotype 2 (AAV2)-based and TTV genotype 19 (TTV19)-based vectors. The hypothesis being tested is that the co-production of single stranded DNA using miniphagemid technology and key AAV or TTV proteins in Escherichia coli can result in AAV-based or TTV-based vectors. The key objectives were therefore: 1) showing recombinant expression of heterologous capsid proteins AAV2 VP1/VP2/VP3 and TTV19 ORF1 in E. coli; 2) producing ssDNA minigenomes flanked by either AAV2 inverted terminal repeat (ITR) or TTV19 untranslated terminal repeat (UTR) sequences; and 3) showing that co-producing protein(s) and ssDNA results in AAV2- or TTV19-based vectors. Results confirmed that AAV2 VP2 and VP3 could be produced in E. coli, albeit expressed primarily as insoluble inclusion bodies. Transformation of cells with a plasmid encoding VP1 resulted in reduced growth and no VP1 was recovered. Expression of TTV19 ORF1 in E. coli produced two histidine-tagged protein products approximately half the size of the expected protein (as previously reported). The ssDNA minigenomes were successfully produced and purified, exhibiting high purity (Objective 2). The central finding was the successful in-bacterial production and purification of functional hybrid vectors, termed AAV-based and TTV-based (Objective 3). Iodixanol gradient ultracentrifugation confirmed particle assembly and density separation. Subsequent qPCR quantification demonstrated high genomic titers in the purified fractions, providing strong evidence of successful ssDNA encapsulation by the heterologous capsids within the E. coli host. The study further found that the TTV19 UTRs likely enhance packaging efficiency in the TTV-based hybrid vector system. In conclusion, this research establishes a robust and scalable E. coli-based platform for producing non-enveloped hybrid viral vectors. This achievement represents a significant step toward revolutionizing gene therapy vector manufacturing, offering a pathway to highly purified, consistent, and affordable therapeutic vectors.
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    Household, Neighbourhood, and Community Contexts and the Mental Health of Immigrants and Immigrant Mothers: An Ecological Perspective
    (University of Waterloo, 2026-01-30) Khan, Tasneem
    Abstract There is growing recognition in the public health field that the determinants of mental health extend beyond biological aspects to include one’s living environment and social context. Research from an ecological perspective has emphasized the importance of contextual factors across multiple levels, such as households and neighbourhoods, in determining mental health. In addition, social positions such as immigrant status, being a woman, and motherhood shape exposure to different contexts and influence mental health outcomes. This dissertation investigates how household, neighbourhood, and community-level factors influence the mental health of immigrants as well as immigrant, racialized and ethnic minority mothers in Canada. In the empirical chapters of this dissertation, Statistics Canada’s survey data were analysed to examine the associations between contextual factors at multiple levels and mental health. First, the Canadian Community Health Survey 2015/16 and the Canadian Index of Multiple Deprivation (CIMD) were used to investigate the association between factors in the household, neighbourhood, and community contexts and the mental health of immigrants in Canada. Second, the General Social Survey 2016, 2017, and 2018 were used to explore how family structure, dwelling characteristics, and household contextual factors relate to the mental health of immigrant and Canadian-born mothers. The final study is a scoping review of the literature from Canada and the United States, focusing on identifying risk and protective factors within the neighbourhood and community contexts affecting the mental health of immigrant and racialized and ethnic minority mothers. Evidence emerged for some factors that can be considered risks and others that are protective of mental health across contextual levels. At the household level, socioeconomic disadvantage in the form of low income adequacy and low household income was related to poor mental health among immigrants and Canadian-born mothers. Being a single versus a partnered mother was also associated with poor mental health outcomes. Factors related to children, such as the age and number of children at home, were not associated with mental health outcomes. At the neighbourhood and community level, negative factors included a weak sense of belonging to the local community and living in an area with higher ethnocultural concentration, reflecting marginalization as measured in the CIMD. Negative factors also included a high proportion of dwellings in need of repair and lower education levels, captured using the situational vulnerability dimension in the CIMD. Findings from the scoping review suggested that deteriorated physical conditions and violence within neighbourhoods negatively impact mental health. On the other hand, a larger household size was associated with lower odds of having a mental health condition and was protective for both immigrant and Canadian-born mothers. While the empirical studies did not directly assess the role of social support and community programming, findings from the scoping review suggest that mental health outcomes are shaped by these factors. Community-based programs related to social and mental health services may help mitigate the effects of socioeconomic disadvantage and foster social inclusion. Social support from friends and family was also found to mitigate the relationship between poor neighbourhood environments and depression among racialized mothers. The findings from all three studies could be used to inform strategies for mental health equity at the community and neighbourhood levels in Canada. This includes interventions at the community level with tailored supports for diverse and larger families to promote the mental well-being of immigrant and racialized populations. In addition, affordable childcare and housing supports for single and low-income mothers could also be beneficial for protecting mental health.
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    Examining Enabling Conditions of Multi-loop Social Learning in Integrated Flood Risk Management: Evidence from Ontario’s Conservation Authorities in a Flood Management Network Context
    (University of Waterloo, 2026-01-30) Ciardulli, Paolo
    Flood risk remains a persistent societal challenge, as no existing measures can offer complete protection against its impacts. Despite advancements in forecasting technologies, infrastructure and policy, flood events continue to result in substantial economic, social and environmental consequences. The complexity of managing flood risk stems from the interaction of dynamic and interrelated factors such as land-use change, risk constructs, governance structures, stakeholder priorities and coordination mechanisms. Integrated Flood Risk Management (IFRM) offers a comprehensive approach, recognizing the need for coordination across governmental levels, sectors and stakeholders while adapting to changing conditions. Within these interconnected socio-ecological systems, continuous learning and adaptation are essential. Social learning, particularly Multi-Loop Social Learning (MLSL), is a key supportive element of IFRM, yet it remains underexplored in this context. This dissertation investigates the presence of theoretically grounded MLSL capacities and enabling conditions in the practices and collaborative processes of Ontario’s Conservation Authorities (CAs). Particular attention is given to their interactions with the broader Ontario flood management network. These MLSL factors are theorized to play a critical role in supporting the development and application of an IFRM strategy. The IFRM strategy used in this research is modeled after a multi-phased, bio-regionally based, iterative, real-world and documented example: the European Union’s Floods Directive. The study examines how MLSL capacities align with the demands of such an IFRM approach in the Ontario context. Therefore, it situates Ontario within a broader Canadian conversation about the intersection of river basin-based water resources management and MLSL. Ontario’s CAs, which are river basin–based organizations with legal mandates in flood risk reduction, served as embed units of analysis within the wider case study (i.e., the CA flood management network) for this research. A two-round Delphi survey was conducted with 20 flood risk management (FRM) experts. Survey questions were designed to reflect MLSL factors derived from a previously developed research framework which focused on said factors in the context of Québec’s watershed management organizations. The modified Delphi approach also made it possible to capture both consensus and divergence between academic and practitioner perspectives. Findings indicate that several enabling MLSL capacities are evident in Ontario’s IFRM setting. These include (1) collaborative partnerships and networks, (2) an intentional approach to learning regarding collaborative processes, (3) sustained participation with governmental stakeholders, (4) cross-sectoral collaboration, (5) internal technical expertise, and (6) learning related to project goals. Respondents attributed these capacities to the CAs’ pivotal roles in flood management networks, long-standing engagement with municipalities and the province, their ecosystem-based approach, and their ability to convene diverse stakeholders across watersheds. CAs were also recognized for their multidisciplinary teams, adaptive management practices, and facilitation skills. Conversely, the study identified several areas where MLSL capacities are lacking. These include (1) shared data access among governmental actors, (2) collaborative decision-making across governmental levels, (3) an enabling democratic environment, (4) in-depth project reflection using formalized assessments, and (5) access to external expertise. Respondents attributed these gaps to uncertainty about data access, staff and funding constraints, inconsistent capacity among CAs, governance limitations, and unclear roles of external experts. These gaps highlight both institutional and policy limitations that impact the potential to fully transition toward IFRM in Ontario. This research isolates and analyzes specific MLSL themes, thus, making it possible to assess specific conditions that enable capacity for MLSL. Two key dimensions emerged: (1) the extent to which MLSL capacities are present and (2) how they manifest across IFRM phases. Together, these insights reveal the degree to which MLSL supports IFRM strategy development and implementation. A cross-comparison with a seminal study found convergence on 9 of 11 MLSL themes. This degree of alignment suggests that MLSL capacity challenges are broadly consistent across Canadian river basin-based water resources management contexts; particularly between Ontario and Québec. This study contributes to scholarly discourse by advancing understanding of MLSL in IFRM settings and offering practical insights for flood management organizations seeking to transition toward more integrated and adaptive approaches. The broader problem this research addressed is the extent to which watershed management agencies, or similar institutions, can effectively transition from one management model to another, particularly when such a transition necessitates the development of specialized MLSL capacities required for implementing the new strategy or model. In parallel, the research highlights policy needs by showing where Ontario’s flood strategy can be reinforced: shared data systems, inclusive decision-making, reflexive evaluation, expanded expertise and sustained multi-sectoral collaboration.
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    Laurentide Ice Sheet dynamics across multiple glacial-interglacial cycles from Quaternary stratigraphic records in the western Hudson Bay Lowland, central Canada
    (University of Waterloo, 2026-01-29) Hodder, Tyler
    Understanding the terrestrial Quaternary stratigraphic record is necessary to reconstruct regional- to continental-scale paleo-ice sheet fluctuations and compare how these events relate to oxygen isotope proxies derived from marine sediments, sea level change, and contemporary ice sheets. Regions that contain an extensive stratigraphic record beyond the last glacial maximum are key to understanding the long-term behaviour of ice sheets and provide field-based constraints for ice-sheet reconstructions and modelling. The Hudson Bay Lowland (HBL) is one of these key regions situated in central Canada that contains a fragmented stratigraphic record of at least the last four Laurentide Ice Sheet (LIS) glaciations. The main objectives of this thesis are to 1) reconstruct the spatio-temporal evolution of the LIS from the Quaternary stratigraphic record of three relatively understudied regions of the western HBL and 2) determine the timing and climate conditions that persisted during ice-free periods across multiple glacial-interglacial cycles. To better understand the fragmented stratigraphic record that is dominated by glacial sediments (till), this thesis developed a hybrid lithostratigraphy-allostratigraphy approach that relies on multi-parameter characterization of tills to establish sediment provenance and the ice-flow direction that deposited the sediment. This included detailed study of 70 sections, the collection of 193 stratigraphic ice-flow indicators (154 till fabrics and 39 lodged clasts) and analysis of 393 till samples. Once the till framework was established, the relative age of each nonglacial bed was then determined using the bounding surfaces of designated till units. At least 18 units have been identified this way and correlated across the western HBL. The nonglacial beds were further characterized to assess the timing of sediment deposition using radiocarbon and optical dating methods and paleo-environmental conditions that existed using pollen and foraminifera analysis. Lastly, stratigraphic frameworks presented herein did not rely on geochronology constraints to anchor correlations and the age of identified interglacial beds can be further tested to confirm the age of interglacial beds. The new stratigraphic framework for the western HBL provides important field-based constraints for LIS reconstructions. This includes evidence that there was asynchronous growth of the two major domes of the LIS during the last two glaciations, with accelerated early growth of the Quebec–Labrador Dome relative to the Keewatin Dome. In each glaciation, the Keewatin Dome becomes more active relatively later in glaciation and persists until deglaciation. During the last glaciation, ice-flowing from the Keewatin Dome likely did not occur until MIS 2 and this S-trending ice-flow transitions into late-glacial SW-trending ice-streams. During the penultimate glaciation (~MIS 6), till deposition by S- to SW-trending ice was extensive and one of the main ice-flow events across the western HBL when the Keewatin Dome was likely situated in northern mainland Nunavut. Furthermore, during deglaciation the Keewatin Dome or an ice divide was likely situated in the western HBL. There is widespread evidence across the western HBL that sediments belonging to at least three pre-Holocene interglacial periods exists, which provides an important archive to understanding past climatic conditions in central Canada. For two of these interglacials there is evidence of marine inundation which likely occurred during Termination II (~130 ka) and Termination III (~243 ka). In the Churchill River region, the marine limits for both marine incursions are higher compared to the Tyrrell Sea (Holocene) marine limit, providing important field-based constraints for LIS modelling. Importantly, new age estimations from the uppermost intertill nonglacial sediments, combined with consideration of the paleobotanical datasets in the western HBL stratigraphic record, suggest that the region was last deglaciated during MIS 5e. This implies that the HBL, and likely Hudson Bay, remained glaciated during MIS 3. The presence of weathered bedrock within the western HBL indicates that glacial erosion of bedrock was negligible in places during the Quaternary Period. Relict landscapes across northeastern Manitoba, such as preserved streamlined landform flowsets that are situated outside the margins of late-glacial ice streams, provide evidence of limited erosion following initial glacial advance into the area. The results of this thesis have provided an updated Quaternary stratigraphic framework for the western HBL, a key region for understanding the long-term evolution of the LIS. The Quaternary stratigraphic record is highly fragmented, which reflects patchy erosion and deposition over multiple glacial-interglacial cycles of the region. The new stratigraphic frameworks developed provide an increased understanding of the growth, evolution and retreat of the LIS during the past two glaciations and insights into pre-Illinoian glaciations, which are essential to improving reconstruction and modelling of the ice sheet throughout the Middle and Late Pleistocene.
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    Correlation-Aware Rendering: Improving Sampling and Denoising for Realistic Image Synthesis
    (University of Waterloo, 2026-01-29) Zhou, Weijie
    In realistic image synthesis, Monte Carlo integration is the foundation of most rendering algorithms, but it inevitably introduces noise. To reduce such noise, advanced sampling strategies—such as Markov chain Monte Carlo (MCMC), resampled importance sampling (RIS), and modern denoising techniques—have been proposed. However, these methods of ten introduce correlations that can manifest as new artifacts. This thesis investigates three distinct research directions, spanning from mitigating correlation to actively exploiting it. The first direction tackles correlation in MCMC methods. Traditional MCMC often suffers from low acceptance rates, producing visually “spiky” noise. We propose combining MCMCwithpathguiding techniques to improve acceptance probabilities, thereby reducing correlation artifact and improving image quality. The second direction addresses correlation artifacts in the widely used Reservoir-based Spatiotemporal Importance Resampling (ReSTIR) algorithm. While ReSTIR achieves ef f icient sampling by reusing samples across pixels and frames, this reuse can lead to blotchy artifacts, as many pixels may end up sharing only a few important samples. Observing par allels between ReSTIR and MCMC, we introduce a new spatiotemporal MCMC framework that replaces reservoir resampling. Applied to both direct illumination and path tracing, our approach significantly reduces correlation artifacts while retaining efficiency. The final direction shifts from reducing correlation to exploiting it. We present a gener alized combination framework that leverages spatial, temporal, and multiscale correlations to reduce error. This method enables robust cross-domain fusion, effectively suppressing systematic artifacts and improving temporal coherence—particularly crucial in animation. Through extensive experiments, we demonstrate that our framework enhances temporal stability, visual appearance, and residual error reduction across diverse rendering scenarios.