Department of Biology Graduate Theses

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    Understanding the Regulation and Function of CDK8 Using Saccharomyces Cerevisiae
    Anbalagan, Bhuvan; Biology; Aristizabal, Maria
    Cdk8 is a conserved protein kinase and a member of the Mediator transcription co-activator complex. Accumulating evidence highlights CDK8 as an oncogene in colorectal cancer, emphasizing the need to understand its function and regulation. Notably, CDK8 amplification or overexpression is observed in approximately 60% of colon cancer tumours and has been detected in melanoma, leukemia, as well as breast, pancreatic, and prostate cancer. Collectively, this evidence has stimulated efforts to develop Cdk8 inhibitors for cancer therapy. Despite a growing interest to target Cdk8 for anti-cancer treatment we have limited information about Cdk8 regulation, a knowledge gap that may complicate efforts to block its activity. To understand the function and regulation of Cdk8, I used the budding yeast model system and leveraged disease-associated variability and recent insight from structural and biochemical analyses. Specifically, using information from primary cancer studies and ClinVar I identified a cluster of CDK8 missense mutations that localize to the kinase ATP binding pocket and sites of interaction with proteins known to regulate Cdk8 kinase activity, that affect CDK8 function. Careful examination of these mutants suggests the existence of a feedback mechanism that regulates Cdk8 protein and mRNA levels. In addition, my work also showed that the interaction between Cdk8 and Med12 regulates CDK8 function in a condition-specific manner. Collectively, this research sheds light on the function and regulation of Cdk8, work that will inform the development of targeted therapies and enhance our understanding of the mechanisms by which Cdk8 contributes to cancer development.
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    Identifying Candidate Genes for Flowering Time and Floral Development in Genome and Transcriptome Assemblies of the Non-Model Plant Lythrum salicaria.
    Fuentes-Vergara, Mabel S.; Biology; Colautti, Robert
    Climate change is leading to environmental shifts, challenging the survival of many organisms. Some invasive species like Lythrum salicaria (purple loosestrife) can rapidly adapt to new conditions and thrive in human-altered habitats, offering a valuable model for studying the ecological and genetic factors that enable species survival under global change. While the ecological factors promoting the invasion and spread of L. salicaria are well-studied, the genetic basis for ecologically important traits is less understood. The aim of this thesis was to develop an annotated genome and transcriptome to investigate the genetic architecture of L. salicaria and the genetic basis of adaptive traits. A draft genome of a diploid ancestor from the native range was assembled using paired-end and mate-pair libraries sequenced on the Illumina HiSeq and MiSeq platforms. Ten transcriptomes were sequenced, representing four tetraploid individuals from the introduced range, and included different samples from the stem, floral meristem, flowers, and fruits of early and late-flowering phenotypes. Additionally, the genome assembly was annotated using the transcriptome as well as sequence-based predictions. The genome assembly was approximately 0.8 Gb in size across 648 scaffolds with 60,656 potential genes. A re-assembly of the transcriptome using the annotated genome resulted in 120,565 transcripts derived from 66,445 potential genes, including isoforms. An enrichment analysis identified 1,946 genes potentially involved in flowering processes, with 1,399 showing protein matches to 124 reviewed flowering-related proteins in the UniProtKB database. Additionally, matches were identified for genes related to stress response and defense metabolites. A key focus was the differential expression analysis of transcripts related to flowering time and floral tissues, providing insights into the genetic factors influencing these traits in L. salicaria. This research enhances the understanding of the genetic architecture of L. salicaria and identifies candidate genes for future investigations into plant genomics and adaptation strategies in changing environments.
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    Assessing the Toxic Effects of “Eco-Friendly” Road De-Icer Alternatives on Freshwater Plankton Communities
    Martin, Troy A.; Biology; Arnott, Shelley
    Increasing use of de-icing salt on roads and paved surfaces is contributing to rising salinity in freshwater, threatening aquatic ecosystems. In response, novel road de-icers advertised as “eco-friendly” have been developed and are widely used in cities across North America. Despite this, testing of the toxicity of road salt alternatives rarely extends beyond individual aquatic species, and community and ecosystem-level testing remain limited. We used outdoor mesocosms at the Queen’s University Biological Station to test how zooplankton communities, important primary consumers in aquatic systems, responded to multiple levels of three de-icers: road salt (NaCl), an organic alternative (beet-juice & salt-brine), and an inorganic alternative (NaCl, CaCl2, MgCl2). We found that both alternatives were toxic to zooplankton and decreased total abundance and affected community indices. Cladocerans and copepods were more sensitive than rotifers to all de-icers. We saw various impacts at the zooplankton species level, indicating differential sensitivities that could impact community composition, species interactions, and ecosystem function. However, the mechanisms of toxicity among de-icers may have differed; a decline in oxygen in the organic alternative correlated with the decline in zooplankton abundance not observed in the other de-icers tested. The inorganic and road salt de-icers also increased the chlorophyll a concentration at the end of the chloride gradient, while the organic de-icer decreased it. These results suggest that some de-icer alternatives might not be as environmentally friendly as advertised despite their recommended and growing use across North America, although more research is needed in impacted lakes.
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    The Impact of Wind Turbines on the Distribution of Wintering and Migrating Raptors
    Mitchell, Kate E.; Biology; Martin, Paul
    Renewable energy sources, including wind power, are rapidly expanding as governments aim to fight climate change. However, wind turbines may negatively affect surrounding wildlife. Raptors are birds of prey and are potentially susceptible to being negatively affected by wind turbines. Raptor collisions with wind turbines are well-studied, but the potential for their spatial displacement due to wind turbines has received less attention. Understanding both collisions and displacement is necessary to comprehend the overall effects of wind turbines on raptors. Amherst Island, Ontario, Canada is renowned for its number and diversity of wintering raptors. Wind turbines were built on the island in 2018. In this study, we used standardized surveys to record the presence, number, and precise location of raptors on Amherst Island during winter and spring migration for three years before (2015, 2016, 2017) and three years after (2019, 2022, 2023) the windfarm was built. We recorded 3,277 observations of raptors which we used to test whether the turbines affected raptor distributions, incorporating both spatial and temporal controls. We found no evidence that any of our six focal raptor species – Northern Harrier (Circus hudsonicus), Bald Eagle (Haliaeetus leucocephalus), Red-tailed Hawk (Buteo jamaicensis), Rough-legged Hawk (Buteo lagopus), Snowy Owl (Bubo scandiacus), or American Kestrel (Falco sparverius) – changed their distributions in response to wind turbines. Similarly, we found no evidence of changes in the distributions of different age classes of Bald Eagle in response to wind turbines. Changes in overall population sizes on Amherst Island for our six focal species, as well as for Short-eared Owl (Asio flammeus) and Northern Shrike (Lanius borealis), mirrored regional trends in abundance, suggesting no impacts of wind turbines on raptor abundance. Overall, despite some collisions between raptors and wind turbines recorded in monitoring studies, we found no evidence of negative impacts of wind turbines on how our focal species use Amherst Island during winter and spring migration. As the need for renewable energy grows, using strong methods to study potential effects of wind turbines on surrounding wildlife will help ensure appropriate sites are chosen for future windfarms.
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    Mapping pathogen distributions and population connectivity of a sentinel Arctic species, the polar bear (Ursus maritimus) across a changing North American Arctic
    Tschritter, Christina; Biology; Lougheed, Stephen C.
    Large-scale environmental shifts are expanding pathogen distributions making many northern species more vulnerable to disease. To understand such rapidly changing host-pathogen dynamics and potentially mitigate impacts of novel pathogens on northern peoples and ecosystems, I quantify population connectivity and pathogen presence in a sentinel Arctic species, the polar bear (Ursus maritimus). Polar bears are apex predators that can provide insight into pathogen distribution and prevalence across marine and terrestrial ecosystems. The focus of my dissertation was to develop molecular tools to monitor polar bear populations and to promote co-management through non-invasive and harvest-based sampling. More specifically I aimed to: (i) Delineate polar bear population structure using genome-wide panels of Single Nucleotide Polymorphic markers (SNPs) to interpret population connectivity that might impact pathogen spread; (ii) Develop and validate a sensitive multiplexed, magnetic-capture, and digital PCR tool for surveillance of five zoonotic pathogens (three bacteria Erysipelothrix rhusiopathiae, Francisella tularensis, and Mycobacterium tuberculosis complex (MTBC), and two parasites T. gondii and Trichinella spp.) relevant to wildlife and human health; and (iii) Quantify the spatial distributions of focal pathogens in polar bear tissues and observe associations between pathogen detections and predictors. Despite the mobility of polar bears and their large home ranges, I found three population clusters that coincide with Arctic ice ecoregions. I made novel pathogen detections (first detection of E. rhusiopathiae in a polar bear, first molecular detection of F. tularensis in the tundra, and the first detection of a MTBC member in Arctic wildlife) and provide insights on how populations might respond to future exposure to novel pathogens. Overall, we found that harvest season and human settlements were important predictors of presence for some pathogens. I envision the establishment of a long-term harvest-based monitoring program that incorporates the powerful molecular tools that we have created, enabling territorial governments to monitor changes in prevalence and/or the geographic advance of select pathogens. The continuation and expansion of this work into a monitoring program would present an unprecedented opportunity to provide critical, real-time, and community-based disease surveillance across the Arctic and ultimately improve opportunities for the co-management of the polar bear species.