Biology Theses and Dissertations

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Open Access
A Bacterial Lytic Polysaccharide Monooxygenase GbpA Promotes Epithelial Proliferation in Drosophila melanogaster
(University of Oregon, 2022-10-26) VanBegue, STEPHANIE; Guillemin, Karen
Animals are colonized by a consortium of microbes that sense and respond to their immediate environments. These microbes, collectively called the gut microbiota, promote epithelial proliferation in a diversity of animal hosts. While the effect of this relationship is well established, the mechanism underlying this response is less understood. In this work, we establish a molecular connection between colonization by the microbiota and the resulting increase in gut epithelial proliferation. We show that different homologs of a highly conserved chitin degrading enzyme promote epithelial proliferation in both zebrafish and fruit flies. Probing the mechanism of this conserved relationship in flies, we show that other enzymes that compromise the chitin lining of the gut will also stimulate epithelial proliferation. Finally, we find that proliferation is a result of innate immune sensing of increased concentration of luminal GlcNAc monomers which are the product of chitin-cleaving enzymes. The comparative work presented in this dissertation explores a new way of thinking of host-microbiome relationships that focuses on microbial function over identity or abundance of specific species.
Open Access
A Developmental Framework for Coupling Neurogenesis to Circuit Formation in Drosophila
(University of Oregon, 2020-02-27) Mark, Brandon; Doe, Chris
Two central questions in neuroscience are how the brain is capable of both generating the diversity of neurons necessary for generating appropriate behaviors and how developmental programs are capable of then wiring these diverse populations of neurons together into functional circuits. While a great deal of progress has been made towards understanding the mechanisms that specify neuronal diversity, it is less clear how these mechanisms might also regulate neuronal morphology and connectivity. In this dissertation, we identified a novel mechanism for diversity generation in the Drosophila central brain. Next, we mapped the developmental origins of seven lineages in the Drosophila ventral nerve cord into a serial-section electron microscopy (SSEM) volume and used this connectome to examine how lineage, hemilineage, and birth order correlate with synaptic targeting and connectivity. Finally, we combined the same SSEM volume with single-muscle calcium imaging to explore how these functional circuits are capable of generating distinct locomotor behaviors. In chapter two, we show that the hormone ecdysone is required to down-regulate early neuroblast temporal identity factors as well as activate later temporal identity factors. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors. In chapter three, we map the developmental origin of neurons from seven neuroblasts and identify each neuron within a complete EM reconstruction of the Drosophila larval CNS. We find that lineages generate a sensory and motor processing hemilineage in a notch-dependent manner. Within each hemilineage, we observe a birth order dependent “tiling” of the neuropil, and neurons with similar temporal identity are enriched for shared connectivity. Thus, diversity generating mechanisms progressively restrict neuropil targeting, synapse localization, and connectivity. In chapter four, we characterize neural circuits generating Drosophila forward and backward locomotion. We show that a subset of MNs change recruitment timing for each behavior. Next, we used a SSEM volume to reconstruct a comprehensive larval PMN-MN connectome. We conclude that different locomotor behaviors are generated by multiple mechanisms: muscle recruitment differences, dedicated PMN/MN connectivity; asymmetric PMN/MN morphology, and behavior-specific PMN activity. This dissertation contains unpublished co-authored material.
Open Access
A Microsporidian Parasite Infects Ribbon Worms of the Genus Maculaura on the Eastern Pacific Coast
(University of Oregon, 2019-04-30) Robbins, Kara; von Dassow, George
The small nemertean Maculaura alaskensis is used as a model for studies of pilidiophoran development. During several microinjection experiments, it became clear several batches of oocytes obtained from wild-caught females contained an intracellular pathogen. Infected oocytes have large vesicles containing dozens to hundreds of refractile oval objects. Examination of oocytes with DIC and confocal microscopy showed the spores within the vesicles were diplokaryotic and contained a coiled tube, traits that are diagnostic of the phylum Microsporidia. The Microsporidia are a group of obligate intracellular parasites that infect cells of protists and animals. No other microsporidian has ever been found infecting cells of nemerteans and the association between M. alaskensis and this microsporidian is, thus far, undocumented. For my thesis, I described morphological characteristics, molecular phylogeny, and geographic range of the microsporidian. Additionally, I observed parasitic influences on development of infected M. alaskensis and explored other potential host species.
Open Access
A Tale of Two Tunicates: Didemnum vexillum and Botrylloides violaceus as Biofouling Agents in Aquaculture
(University of Oregon, 2018-09-06) Knorek, Zofia; Galloway, Aaron
Invasive colonial tunicates pose substantial economic threat to the shellfish aquaculture industry, but their population dynamics and ecological impacts are highly variable and region-specific. This thesis contributes to our regional understanding of two such tunicates in Oregon. The first chapter explores the population dynamics of Didemnum vexillum, one of Oregon’s top 100 most dangerous invasive species, at an oyster farm. From May 2011 to 2016 the population fluctuated extensively, though did not exhibit any net growth over the study period. In the second chapter, I demonstrate that Botrylloides violaceus had no impact on the growth, condition, or organic composition of oysters and mussels grown in a simulation of longline aquaculture. Together, these studies paint a cautiously positive outlook for the shellfish aquaculture industry in Oregon. This thesis includes previously unpublished co-authored material.
Open Access
Actomyosin Spatiotemporally Regulates Par Polarity Dynamics To Create Neural Stem Cell Asymmetry
(University of Oregon, 2021-09-13) Oon, Chet Huan; Prehoda, Kenneth
Pattern formation, or specifically symmetry breaking, is a fundamental process essential for proper asymmetric cell division. In asymmetrically dividing stem cells, the evolutionarily conserved Par polarity complex localizes to a discrete Par domain to facilitate unequal distribution of fate determinants into the daughter cells–thereby ensuring a binary cell division outcome where daughters will acquire distinct fates. Hence proper asymmetric cell division requires the spatiotemporal distribution of Par proteins to be precisely coordinated. While a number of studies have been conducted to understand how Par activity creates downstream asymmetry, how the Par complex acquires asymmetry remains unclear. Two standing models exist to explain for how Par proteins can become polarized. In the one-cell stage C. elegans embryo, gradients of contractile force created by the cortical actomyosin cytoskeletal network generates cortical flow towards the anterior pole. Concurrently, symmetrical Par proteins that are entrained within the network becomes advected via bulk motion of the cortex, consequently becoming anteriorly segregated. In Drosophila neuroblasts, Par complex exchanges between the unpolarized, cytoplasmic and polarized, apical states; it is thus thought to become polarized to the apical domain via a direct, asymmetric targeting mechanism. In this dissertation, we examined the spatiotemporal distribution profile of cortical Par proteins and actomyosin in mitotic neuroblasts using a full volume, rapid live imaging approach to capture change in cortical protein distribution as they transition from an unpolarized to a polarized state. In the second chapter, we characterized the Par protein dynamics and investigated if the actomyosin network is essential for Par dynamics. This study demonstrated that Par polarization is a dynamic, multistep process, consisting of asymmetric targeting of cytoplasmic Par into discrete, apical foci and F-actin dependent coalescence of Par foci at the apical pole. In the third chapter, we determined the cortical dynamics of actomyosin and identified that coalescence is spatiotemporally linked to myosin II driven flow. Our studies suggest a conserved role for actomyosin in Par polarity in C. elegans embryos and Drosophila neuroblasts. This dissertation contains previously published and unpublished co-authored material. Live imaging movies of Par proteins and actomyosin are attached in the supplemental files associated with this dissertation.
Open Access
An Actin Cross-Linking Effector of the Vibrio Type Six Secretion System Increases Intestinal Motility Through Macrophage Redistribution
(University of Oregon, 2024-03-25) Ngo, Julia; Guillemin, Karen
Host-microbe interactions within the gastrointestinal tract have long been recognized as pivotal for maintaining physiological balance. However, the intricate mechanisms underlying these interactions remain enigmatic. This study delves into the complex world of host-microbe relationships, focusing on the Vibrio type VI secretion system (T6SS), particularly the actin cross-linking domain (ACD) of the valine-glycine repeat G (VgrG-1) protein. We explore the role of the ACD in altering intestinal motility in larval zebrafish. Our findings reveal a fascinating mechanism underlying these interactions. Vibrio, known for its pathogenic potential, instigates cellular death and tissue damage within the vent region of the zebrafish intestine. This destructive action triggers an immune response within macrophages from their typical habitat in the midgut to the affected vent region. This revelation emphasizes the disruptive influence of bacterial pathogenesis on macrophages and, by extension, their role in regulating intestinal motility. Our findings provide valuable insights into the intricacies of intestinal motility regulation in the context of host-microbe interactions. In conclusion, this research broadens our understanding of the mechanism by which gut microbes influence host physiology, specifically in the context of intestinal motility. The presence of bacterial pathogenesis and its influence on macrophages, coupled with insights into the intricate dynamics of host-microbe interactions, underscores the significance of this work. This intricate interplay between microbes and host systems not only reveals microbial influences on host physiology but also highlights the mechanisms employed by the host to maintain homeostasis.
Embargo
Analysis of active neural circuits and synaptic mechanisms of memory
(University of Oregon, 2018-10-31) DeBlander, Leah; Kentros, Clifford
One feature of the brain is that different parts of it respond to different stimuli. This means not all brain regions or neurons within those regions are active at a given moment. This feature of the brain gives it the ability to encode and store a wide range of stimuli that are then used to make predictions about a changing external environment. Activation of non-overlapping neural populations is fundamental to the ability to encode a wide range of stimuli to represent a changing environment. To examine the limits of this idea we used genetic tools to label active cell populations following a neutral stimulus presentation or a learned negative association with the same stimulus. The study examined the degree of similarity between these active populations by comparing key features of the active neurons including gene expression and monosynaptic inputs. Another feature of the brain is its ability to store information. In a neural population recently activated by a salient stimulus, molecular processes occur that result in the formation and maintenance of a memory. Collectively these processes are referred to as plasticity, and act on short and long time scales to strengthen the connections between active neurons and weaken the connections between inactive ones. Plasticity processes are not only necessary for the formation and storage of memories but also for wiring up the nervous system during development. A molecule called ZIP has been shown to erase memories months after formation and specifically affects plasticity on longer time scales. However, the effects of ZIP on the developing brain are not well understood and difficult to study using ZIP’s typical delivery method of injection into the brain. To facilitate a developmental study of ZIP’s effects, we made a genetic tool that can specify where and when ZIP is delivered to the brain. Results of the study indicated that males were particularly vulnerable to ZIP during early development while females were unaffected. Together these results provide insight into the limits of information coding potential at the anatomical level and reveal a fundamental difference in plasticity processes in males and females.
Open Access
An analysis of the distribution of a commensal polynoid on its hosts
(Thesis (Ph.D.)--Oregon, Dept. of Biology, 1968) Palmer, John Beach, 1941-
Open Access
Analysis of the lower distributional limit of callianassid shrimp in South Slough National Estuarine Research Reserve
(Thesis (M.S.)--University of Oregon, 1993., 1993) Miner, Jonathan Neal, 1969-
The lower distributional limits (fronts) of callianassid shrimp populations were observed at five sites in South Slough, Coos Bay estuary, Oregon. Fronts at four sites exhibited similar shoreward-seaward movements while the remaining site showed drastic population reductions. Shrimp density and body size were found to be significantly greater above than below the front. There was no consistent pattern found in grain size or interstitial water content across the front. In a controlled predator-exclusion experiment, resulting shrimp densities were not significantly different among treatments. Front shifts showed no pattern in response to treatments. These results imply that fish predation is not responsible for front placement. Trawls taken on both sides of the front produced similar densities of a predatory fish, Leptocottus armatus. Because predation pressure was calculated to be roughly equal above and below the front, Leptocottus is not expected to be responsible for position and movements of these fronts.
Open Access
An analysis of the maintenance and control of a polymorphism in the limpet Acmaea digitalis Eschscholtz
(1968-12) Giesel, James Theodore, 1941-
Open Access
Argon-nitrogen ratios in the swimbladder of physostomous fishes with particular reference to the rainbow trout, Salmo gairdnerii
(Thesis (Ph.D.)--University of Oregon, 1973, 1973-06) Buell, James Whitton, 1944-
Open Access
Aspects of antennal gland function in the dungeness crab, Cancer magister (Decapoda, Brachyura)
(University of Oregon theses, Dept. of Biology, Ph.D., 1978, 1978-06) Holliday, Charles Walter, 1946-
Open Access
Assembly of microbial communities associated with the developing zebrafish intestine
(University of Oregon) Burns, Adam; Bohannan, B. J. M.
The communities of microorganisms associated with humans and other animals are characterized by a large degree of diversity and unexplained variation across individual hosts. While efforts to explain this variation in host-associated systems have focused heavily on the effects of host selection, community assembly theory emphasizes the role of dispersal and stochastic demographic processes, otherwise known as ecological drift. In this dissertation, I characterize the communities of microorganisms associated with the zebrafish, Danio rerio, intestine, and assess the importance of microbial dispersal and drift to their assembly. First, I describe changes in the composition and diversity of the zebrafish intestinal microbiome over zebrafish development and show that while host development is a major driver of community composition over time, there remains a large amount of unexplained variation among similar hosts of the same age. I go on to show that random dispersal and ecological drift alone in the absence of host selection are sufficient to explain a substantial amount of this variation, but the ability of these processes to predict the distribution of microorganisms across hosts decreases over host development. Finally, I present an experimental test of dispersal in host-associated systems, and show that not only does dispersal among individual zebrafish hosts have a large impact on the composition and diversity of associated microbial communities, but it can also overwhelm the effects of important host factors, such as the innate immune system. As a whole, this work demonstrates that the composition and diversity of microbial communities associated with animal hosts are not solely the result of selection by the host environment, but rather dispersal and stochastic processes have important and often overwhelming effects on their assembly. To fully understand the assembly of host-microbe systems, we must broaden our focus to include scales beyond that of an individual host and their associated microorganisms.
Open Access
Associative behavior of the arrow goby, Clevelandia ios (Jordan and Gilbert) and the ghost shrimp, Callianassa californiensis Dana
(University of Oregon theses, Dept. of Biology, M.S., 1980, 1980-12) Hoffman, Carol Jane, 1956-
Open Access
Atypical protein kinase C regulates Drosophila neuroblast polarity and cell-fate specification
(University of Oregon, 2008-09) Atwood, Scott X.
Cellular polarity is a biological mechanism that is conserved across metazoa and is used in many different biological processes, one of which is stem cell self-renewal and differentiation. Stem cells generate cellular diversity during development by polarizing molecular determinants responsible for directing one daughter cell to maintain stem cell-like qualities and the other daughter cell to initiate a specific cell fate. The stem cell self-renewal versus differentiation choice is critical to avoid overproliferation of stem cells and tumor formation or underdevelopment of tissues and early animal death. Drosophila neural stem cells (neuroblasts) undergo asymmetric cell division (ACD) to populate the fly central nervous system and provide an excellent model system to study processes involving cellular polarity, ACD, stem cell self-renewal, and differentiation. Neuroblasts divide unequally to produce a large, apical self-renewing neuroblast and a small, basal ganglion mother cell that goes on to divide and form two neurons or glia. In this way, a small population of neuroblasts can give rise to thousands of neurons and glia to generate a functional central nervous system. Atypical Protein Kinase C (aPKC) is critical to establish and maintain neuroblast polarity, ACD, stem cell self-renewal, and differentiation. aPKC is part of the evolutionarily conserved Par complex, whose other members include Bazooka and Par-6, and they localize to the neuroblast apical cortex and function to restrict cell-fate determinants into one daughter cell. How aPKC is asymmetrically localized and how its activity translates into cell-fate specification are of incredible importance as apkc mutants where localization is disrupted no longer segregate cell-fate determinants. This work will show that Cdc42 recruits the Par-6/aPKC complex to the neuroblast apical cortex independent of Bazooka. Once there, aPKC phosphorylates the cell-fate determinant Miranda to exclude it from the apical cortex and restrict it basally. Par-6 and Cdc42 regulate aPKC kinase activity though inter- and intramolecular interactions that allow high aPKC kinase activity at the apical cortex and suppressed activity elsewhere. Cdc42 also functions to keep aPKC asymmetrically localized by recruiting the PAK kinase Mushroom bodies tiny to regulate cortical actin and provide binding sites for cortical polarity determinants. This dissertation includes previously published co-authored material.
Open Access
Audiovisual Integration in the Saccadic System of the Barn Owl
(University of Oregon, 2006-12) Whitchurch, Elizabeth A., 1976-
Survival depends on our ability to detect and integrate sensory information from multiple modalities, allowing for the most efficient behavioral response. For example, barn owls must combine sights and sounds from the environment to localize potential prey. A vole scurrying through a drift of dried leaves is more likely to meet its doom if a nearby owl can both faintly see and hear it. How does the brain take two physically discreet inputs and combine them into a unified representation of the surrounding multisensory world? Moreover, how is this internal representation transformed into the most efficient behavioral response? This dissertation comprises original research addressing these questions in the barn owl with two distinct approaches: First, Chapters II and III describe orientation behavior in response to auditory, visual, and audiovisual stimuli. Chapter II probes the effect of stimulus strength on saccadic behavior and the nature of audiovisual integration, and was taken from a co-authored publication. Chapter III explores the behavioral consequence of an induced stimulus asynchrony in audiovisual integration and was taken from a co-authored manuscript being prepared for publication. The second experimental approach is described in Chapters IV and V. These chapters probe the physiological basis of saccadic behavior by measuring single-neuron responses to auditory, visual, and audiovisual stimuli. Chapter IV describes how auditory responses of neurons from the external nucleus of the inferior colliculus depend on sound pressure level. Chapter V describes activity of optic tectum neurons in response to auditory, visual, and audiovisual stimuli. The behavioral findings described herein suggest that barn owls often incorporate both the speed of the auditory system and the accuracy of the visual system when localizing a multisensory stimulus, even when the two modalities are presented asynchronously. The physiological studies outlined in this dissertation show that sensory representations in the midbrain can be used to predict general trends in saccadic behavior: Neuronal thresholds were within the range of observed behavioral thresholds. Responses to multisensory stimuli were enhanced relative to unisensory stimuli, possibly corresponding to enhanced multisensory behavior. These data support fundamental rules in multisensory integration that may apply across species.
Open Access
Autoinducer-2 Quorum Sensing Regulation of Bacterial Colonization and Population Distribution in the Zebrafish Intestine
(University of Oregon, 2021-04-29) Banuelos, Maria; Guillemin, Karen
Quorum sensing is a mode of bacterial communication that relies on the production and secretion of signaling molecules known as autoinducers. Group-wide detection of autoinducers gives rise to collective gene expression patterns that make coordinated group behaviors possible. Behaviors vary across bacterial species but often include: secretion of virulence factors, changes in motility, and biofilm formation. While many autoinducers exhibit high specificity and are used to foster intraspecies communication, one molecule known as Autoinducer-2 (AI-2) is produced and detected by numerous bacterial species. Interestingly, while AI-2 is known to mediate aggregation and biofilm formation of bacteria through the traditional gene regulatory mechanisms, it uniquely can also do so through the use of chemotaxis signaling. For example, Helicobacter pylori perceives AI-2 as a chemorepellent and in turn this chemorepulsion response results in cell dispersal from biofilms. Conversely, in Escherichia coli AI-2 induces cell aggregation via gene expression changes and by serving as a chemoattractant that recruits cells to aggregates. Currently much of the research involving AI-2 has been carried out in monoculture in vitro biofilms and has focused on the role of AI-2 as a mediator of biofilm formation and biofilm membership. Here we investigate the role of AI-2 in colonization and spatial distribution of bacterial communities inside an animal host. To address this we colonized larval zebrafish with wild type E. coli, an AI-2 synthesis mutant luxS, or an AI-2 signaling mutant lsrR. We then used a combination of plate based assays and live imaging to determine the abundance and spatial distribution of the gut bacteria. We observed that in a mono-association, E. coli mutants lacking the ability to produce or detect AI-2 showed increased intestinal abundance. Additionally, we observed differing spatial localizations between populations of luxS bacteria that had been untreated or treated with AI-2. Populations exposed to AI-2 localized more distally along the axis of the intestine, consistent with increased displacement. Further, we showed that native gut bacteria of the zebrafish exhibit analogous responses to AI-2, indicating that interspecies AI-2 signaling could play an important role in microbiome composition and biogeography. This dissertation includes previously unpublished co-authored material.
Embargo
Bacterial Colonization Dynamics and Ecology of the Developing Zebrafish Intestine
(University of Oregon, 2013-10-03) Stephens, William; Eisen, Judith
Human intestinal microbiomes exhibit a large degree of interindividual compositional variation. Animal models, such as the zebrafish, facilitate the design of controlled and highly replicated studies that allow us to understand the normal variation in vertebrate intestinal composition and to study the rules guiding normal assembly of these complex communities. The smaller intestinal size and high fecundity of the zebrafish allow us to fully sample the intestinal contents of many animals, while the optical transparency allows direct in vivo observation of fluorescently labeled bacterial species within the intestine. The studies in this dissertation utilize these advantages to investigate the composition, colonization dynamics and functional requirements for colonization in the vertebrate intestine. We first describe the taxonomic composition and diversity of the zebrafish intestinal microbiota from wild-caught and domesticated zebrafish. In the process, we identify a set of core bacterial genera that are consistently present in zebrafish intestines. We then use species from two of these genera in subsequent studies to gain a detailed understanding of the colonization dynamics and genetic requirements of the two species. We initially describe the application of light sheet microscopy to imaging the zebrafish intestine and associated colonizing bacteria. We find that a single species, Aeromonas veronii, does not occupy the entire intestinal space and that competition within the same species appears to prevent further colonization. These results are extended to a zebrafish isolated Vibrio species as well as A. veronii by tagging bacteria with transposon insertions and tracking the changes in colonizing population sizes. These insertion libraries also identify genes in each bacterial species that are important in the process of colonization, highlighting the key role for motility and chemotaxis in this process. The descriptions and methods discussed in this dissertation advance the use of this important model organism towards the understanding of vertebrate host-microbial interactions. This dissertation includes previously published co-authored material as well as unpublished co-authored material.
Open Access
Bacterial Regulation of Host Pancreatic Beta Cell Development
(University of Oregon, 2018-04-10) Hill, Jennifer; Guillemin, Karen
Diabetes is a metabolic disease characterized by the loss of functional pancreatic beta cells. The incidence of diabetes has risen rapidly in recent decades, which has been attributed at least partially to alterations in host-associated microbial communities, or microbiota. It is hypothesized that the loss of important microbial functions from the microbiota of affected host populations plays a role in the mechanism of disease onset. Because the immune system also plays a causative role in diabetes progression, and it is well documented that immune cell development and function are regulated by the microbiota, most diabetes microbiota research has focused on the immune system. However, microbial regulation is also required for the development of many other important tissues, including stimulating differentiation and proliferation. We therefore explored the possibility that the microbiota plays a role in host beta cell development. Using the larval zebrafish as a model, we discovered that sterile or germ free (GF) larvae have a depleted beta cell mass compared to their siblings raised in the presence of bacteria and other microbes. This dissertation describes the discovery and characterization of a rare and novel bacterial gene, whose protein product is sufficient to rescue this beta cell developmental defect in the GF larvae. Importantly, these findings suggest a possible role for the microbiota in preventing or prolonging the eventual onset of diabetes through induction of robust beta cell development. Furthermore, the loss of rare bacterial products such as the one described herein could help to explain why low diversity microbial communities are correlated with diabetes.
Open Access
Bacterial Stimulation of Intestinal Proliferation via the Wnt Pathway in Zebrafish
(University of Oregon, 2011-12) Neal, James Thomas
This dissertation describes research into microbial influences on host signaling in the zebrafish intestine. Vertebrate organisms are consistently exposed to microbes, especially on epithelial tissues that are exposed to the environment, such as the skin and the gastrointestinal tract. The close association between these tissues and microbes over time has resulted in a symbiotic state, whereby microorganisms have gained the ability to utilize vertebrate epithelia as a niche for replication and the acquisition of nutrients. These associations run the gamut from beneficial to exceedingly pathogenic and often involve complex bidirectional signaling between microbe and host. Microbial signals can interact with host cell pathways involved in a wide range of cellular processes. Here, we describe our investigations into one such pathway, the Wnt signaling pathway, and how microbial activation of Wnt signaling can translate into alterations in cell proliferation and homeostasis in the intestinal epithelium of the teleost fish Danio rerio. We report that epithelial cell proliferation in the developing zebrafish intestine is stimulated both by the presence of the resident microbiota and by activation of Wnt signaling and demonstrate that resident intestinal bacteria enhance the stability of β-catenin in intestinal epithelial cells, promoting cell proliferation in the developing vertebrate intestine. We also describe how transgenic expression of the bacterial effector protein CagA from the human gastric pathogen Helicobacter pylori is capable of causing significant overproliferation of the intestinal epithelium and adult intestinal hyperplasia, as well as significant upregulation of the Wnt target genes cyclinD1 and the zebrafish c-myc ortholog myca. We show that co-expression of CagA with a mutant allele of the β-catenin destruction complex protein Axin1 resulted in a further increase in intestinal proliferation, while co-expression of CagA with a null allele of the essential β-catenin transcriptional cofactor Tcf4 restored intestinal proliferation to wild-type levels. These results suggest that CagA activates canonical Wnt signaling downstream of the β-catenin destruction complex and upstream of Tcf4. Our studies provide in vivo evidence of Wnt pathway activation by CagA and implicate this activation in CagA-induced epithelial overproliferation, an early step in gastrointestinal cancer development. This dissertation contains both my previously published and unpublished co-authored material.