Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item Phylogenomics, Systematics, and Evolution within the Nudibranch Group Cladobranchia (Mollusca: Gastropoda)(2017) Goodheart, Jessica Ann Marie; Cummings, Michael P; Collins, Allen G; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)To truly understand evolution, we must document patterns of variation in traits – ranging from anatomical features of individuals to geographic ranges of species – to gain insights into the mechanisms that lead to changes in diversity through time. This type of work requires a robust historical context of evolutionary relationships in order to make comparisons across taxa and inferences about past events. My dissertation provides a thorough phylogenetic analysis of the marine gastropod group Cladobranchia (Mollusca) to better understand the evolution of defensive capabilities within the clade. In the absence of a protective shell, lineages within Cladobranchia have evolved a diverse array of alternative defense mechanisms, including the use of stinging organelles (nematocysts) acquired from their cnidarian prey. It has been hypothesized that incorporation of nematocysts as a defensive strategy may have been an evolutionarily important event that led to large-scale diversification within this group. As such, understanding the steps involved in the evolution of this ability is necessary for evaluating this hypothesis. A major objective for my dissertation has been to use transcriptome (RNA-Seq) data from 37 species in Cladobranchia in order to generate a well-supported phylogenetic hypothesis of Cladobranchia. This research has produced the most highly supported phylogenetic tree of Cladobranchia thus far and contributes to confidence in the efficacy of genomic data to resolve relationships among gastropod lineages. As I have been able to expand this phylogenetic hypothesis with additional taxon sampling, including molecular data from a further 60 species, I have been able to provide context for understanding the evolutionary steps that led to the ability to sequester nematocysts. This phylogeny was then combined with morphological data from 50 nematocyst sequestering species within Cladobranchia to allow for a more detailed reconstruction of the evolution of nematocyst sequestration and prey preference within this clade. Overall, this work builds knowledge of the relationships among major lineages within Cladobranchia, and has substantially increased understanding of the evolution of morphological and ecological characters in this group.Item Simultaneous transcriptome profiling of Trypanosoma cruzi parasites and their human host cells.(2014) Li, Yuan; El-Sayed, Najib M; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The genome of the kinetoplastid parasite Trypanosoma cruzi, causative agent of Chagas disease, was published nine years ago, yet a systematic and comprehensive analysis of the transcriptomes of the parasite and the human host has not been conducted. The parasite responds rapidly to transmission between arthropod vectors and mammalian hosts by undergoing complex cellular differentiation processes that are not well understood. In this study, we generated the first transcriptome map for both T. cruzi and infected human host cells across the infection cycle including time points of 4, 6, 12, 24, 48 and 72 hours post invasion with the next generation RNA sequencing technology (RNA-Seq). We also captured the transcriptome of the parasite in its bloodstream form (trypomastigote) and its replicative form inside insect vector (epimastigote). We successfully mapped transcribed regions for the pathogen at single nucleotide resolution on a genomic scale and characterized the RNA processing (trans-splicing and polyadenylation) events across its various developmental stages. Here we report the prevalent heterogeneity of RNA processing sites across the genome. We also note the preference of different primary sites in various developmental stages presenting as a potential and interesting approach of posttranscriptional regulation, which may hypothetically contribute to the survival of the parasite across different environments. Our work has significantly enhanced the current genome annotation of T. cruzi. In addition, using the T. cruzi and human genome sequence as reference, we explored these data with informatics tools to identify genes with significant regulation and successfully profiled gene expressions from both species simultaneously. We examined the subsets of differentially expressed genes both in the parasite and the host cell over the course of the infection to understand the mechanisms of invasion and intracellular survival strategy as well as host-pathogen interactions. T. cruzi genes that were significantly regulated during the infection process might present as new targets for drug development, whereas human genes that were significantly regulated might signal the immunoinflammatory response triggered by the manipulation of the parasite. Furthermore, we investigated the gene expression patterns of T. cruzi across its different developmental stages, clustered gene with similar patterns, and identified possible sequence motifs in coexpressed gene clusters.Item Transcript assembly and abundance estimation with high-throughput RNA sequencing(2010) Trapnell, Bruce Colston; Salzberg, Steven L; Computer Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)We present algorithms and statistical methods for the reconstruction and abundance estimation of transcript sequences from high throughput RNA sequencing ("RNA-Seq"). We evaluate these approaches through large-scale experiments of a well studied model of muscle development. We begin with an overview of sequencing assays and outline why the short read alignment problem is fundamental to the analysis of these assays. We then describe two approaches to the contiguous alignment problem, one of which uses massively parallel graphics hardware to accelerate alignment, and one of which exploits an indexing scheme based on the Burrows-Wheeler transform. We then turn to the spliced alignment problem, which is fundamental to RNA-Seq, and present an algorithm, TopHat. TopHat is the first algorithm that can align the reads from an entire RNA-Seq experiment to a large genome without the aid of reference gene models. In the second part of the thesis, we present the first comparative RNA-Seq as- sembly algorithm, Cufflinks, which is adapted from a constructive proof of Dilworth's Theorem, a classic result in combinatorics. We evaluate Cufflinks by assembling the transcriptome from a time course RNA-Seq experiment of developing skeletal muscle cells. The assembly contains 13,689 known transcripts and 3,724 novel ones. Of the novel transcripts, 62% were strongly supported by earlier sequencing experiments or by homologous transcripts in other organisms. We further validated interesting genes with isoform-specific RT-PCR. We then present a statistical model for RNA-Seq included in Cufflinks and with which we estimate abundances of transcripts from RNA-seq data. Simulation studies demonstrate that the model is highly accurate. We apply this model to the muscle data, and track the abundances of individual isoforms over development. Finally, we present significance tests for changes in relative and absolute abundances between time points, which we employ to uncover differential expression and differential regulation. By testing for relative abundance changes within and between transcripts sharing a transcription start site, we find significant shifts in the rates of alternative splicing and promoter preference in hundreds of genes, including those believed to regulate muscle development.