University Archives

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Welcome to the University Archives electronic records community. The University Archives community in Scholars’ Bank is for university records in digital form. The material contained in Scholars’ Bank represents a small portion of the institutional records housed in University Archives. If you are interested in other historic or contemporary records not seen here, please contact Special Collections and University Archives at spcarref@uoregon.edu or 541-346-3068.

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Open Access
Cell Specific Responses to Microbiota Play Global Roles in Host Development & Homeostasis
(University of Oregon, 2022-05-10) Massaquoi, Michelle; Guillemin, Karen
Resident microbes are a fixture within all animal life and impact diverse aspects of host biology ranging from metabolism, training of the immune system to identify pathogens but tolerate commensals, and tissue development. An animal host’s microbiota encompasses the consortium of bacteria, fungi, archaebacteria and viruses that live on and within them. Animal intestines harbor the highest density of microbes and across model organisms the microbiota has shown to play important roles in the development of organs both proximal and distant to the digestive system. Although pioneering work has significantly increased our understanding of the intricate dynamics within host-microbe interactions and has fundamentally altered how we define animal biology, the mechanisms behind these interactions and the extent that they influence host tissues globally is largely unknown. This dissertation describes the work that characterizes which cell types of the developing host are responsive to the microbiota in the model vertebrate, the larval zebrafish. This work also investigates the mechanism by which a bacterial-secreted protein induces the proliferation and development of the insulin-producing beta cells in the larval pancreas.
Open Access
Fish Out of Water: Understanding the Impacts of Regional Species Pool Variation on Local Community Assembly in a Host-Microbiome Model System
(University of Oregon, 2024-08-07) Evens, Kayla; Cresko, William
The host-microbiome is essential to many aspects of host health and function, and acts as a useful model system in which to investigate broader questions of community assembly. Since the composition of host-microbiomes is, in part, determined by the input of microbes from the surrounding environment, it is integral to understand how variation in the environmental microbiome may influence host-microbiome assembly. For my dissertation research, I used a species pool conceptual framework to investigate drivers of variation in the microbiomes of aquaculture research facilities and the fish they house. Zebrafish (Danio rerio) are used extensively as model organisms in scientific research, especially in studies investigating host-microbiome dynamics. For in-vitro experimentation utilizing model organisms, we rely on the reproducibility of results to make broadly applicable conclusions about the host-microbiome. However, evidence suggests that inter-facility variation may influence zebrafish gut microbiome composition via acquisition of microbes from the environment, potentially leading to phenotypic differences among fish housed at different aquaculture facilities. To investigate the relationship between aquaculture facility water and fish gut microbiomes, I first characterized spatial and temporal variation across multiple aquaculture facilities on the University of Oregon campus. Facility water microbiota not only varied over time, but patterns of spatial variation in each facility were consistent despite differences in host species. I then used this information to guide an expanded, intensive sampling of water and fish across four zebrafish facilities in Oregon and Norway. I observed significant variation in microbiome composition both within and between facility water systems and zebrafish gut samples. Further, there was evidence that variation in the water microbiome was a source of variation in zebrafish gut microbiomes. Finally, as differences in facility management and technical specifications can make directly linking microbiome variation in the water to variation in fish difficult, I attempted to isolate the effects by experimentally manipulating the water microbiome in a laboratory study using germ-free larval fish. My results indicate that microbial inputs from live feed overwhelmed any potential influence of water microbiome variation in early-life microbiome assembly. Overall, this dissertation provides a comprehensive look at the drivers of environmental microbiome variation and how these may mediate aspects of host-associated microbiota. My results have implications for fish microbiome research and suggest that research conducted with zebrafish sourced from a single facility may be heavily influenced by facility-specific effects.
Open Access
Investigating Multi-Species Interactions and Spatial Structure of Gut-Bacterial Communities using Live Imaging
(University of Oregon, 2022-10-26) Sundarraman, Deepika; Parthasarathy, Raghuveer
Animal intestines harbor hundreds of microbial species that play a crucial role in host health and development. Despite their importance, many questions about the rules that govern community assembly in these complex environments remain unanswered and almost impossible to study in humans. For example, is it possible to construct multi-species communities from an understanding of pairwise interactions? What is the role of spatial structure and timing in community assembly? How do species' spatial structure and interactions affect the host? We focus on addressing these questions using a consortium of gut bacterial species, native to the vertebrate model organism of larval zebrafish. We first characterize pairwise interactions between a consortium of 5 gut bacterial isolates in 2-species and 5-species competition experiments using an interaction model and find evidence for higher order interactions that dampened strong pairwise competition and enabled coexistence in 5-species communities. We next focus on a specific pair showing strong pairwise competition in 2-species experiments.Using light sheet fluorescence microscopy, we illuminate on the role of spatial structure in the competition between two highly aggregated species localized in the intestinal midgut, namely strains of genera \textit{Aeromonas} (AE) and \textit{Enterobacter} (EN). We test whether altering aggregation and localization behavior impact this interaction using a bacterial strain \textit{Aeromonas-MB4}, derived from parental AE and composed mostly of planktonic cells that are anterior localized. When AE-MB4 invades fish colonized with EN, it induces disaggregation of the highly aggregated EN strain, an effect weakened in the presence of the other 4 species. Additionally, we observe that AE-MB4 induces increased inflammation compared to the aggregated parental AE strain, suggesting possible links between spatial structure and host inflammation. These studies illustrate the complex ways in which species interact with each other and impact the host and that multi-species gut bacterial communities are capable of showing resilience by dampening strong competition effects.
Open Access
Learning Biophysical Rules of Gut Bacterial Communities Through Live Imaging of Zebrafish
(University of Oregon, 2020-09-24) Schlomann, Brandon; Parthasarathy, Raghuveer
Vast communities of microorganisms inhabit the gastrointestinal tracts of humans and other animals, where they influence diverse aspects of animal health and disease. Our understanding of the types of microbes present in the intestine and the genes that they carry has grown tremendously in recent years, but despite this progress, we are still unable to predict the abundances of microbial strains in the gut and their impact on host phenotypes. This deficiency limits our abilities to uncover causal mechanisms mediating host-microbe interactions and to rationally design novel therapeutic strategies. A major barrier to achieving these goals is our limited ability to experimentally probe the spatial organization of gut bacterial communities, which is thought to be a key driver of microbiota dynamics, but which is largely inaccessible in most systems. This dissertation work addresses these knowledge gaps by combining quantitative theory with controlled experiments in a model system that can uniquely surmount these technical challenges. The larval zebrafish is an optically transparent, model vertebrate that is amenable to live imaging studies, in which bacteria in the gut can be directly visualized and studied in situ. Through this approach, we discovered that the biophysical properties of bacteria in the gut, especially their aggregation and swimming behaviors, coupled to intestinal fluid flows, determine in robust but probabilistic ways several large-scale features of whole bacterial populations. These features include global spatial distributions of bacteria throughout the gut, bacterial population dynamics, both at baseline and in response to perturbations like antibiotics, and the ability of bacteria to stimulate immune responses. Through the study and validation of phenomenological models, we argue that these effects are generic and manifest in other animals, including humans, and suggest new strategies to harness these effects for precision microbiome engineering.
Open Access
The Role of Cilia Motility in Axial Morphogenesis
(University of Oregon, 2024-08-07) Irons, Zoe; Grimes, Daniel
The spine is the core of the vertebrate body axis, providing structural support and playing a role in establishing body shape. The linearity of the spine is essential for proper function. Scoliosis, or curvature of the spine, is present in 3-4% of the human population and can cause chronic pain as well as compression of the lungs and heart in severe cases. In this dissertation, I used zebrafish to study the role of cilia motility in morphogenesis of the body axis and the development of scoliosis. Previous work has established cilia motility as essential for zebrafish embryos to uncurl their bodies from around the yolk during the first 24 hours post fertilization. In Chapter I, I found that the protein Daw1 regulates the timely onset of cilia motility, and that embryos are able to remodel their body axes up to 3 days post fertilization. In Chapter II, I investigated factors functioning downstream of cilia motility that control body and spine morphogenesis. The Reissner fiber assembles downstream of cilia motility. Using zebrafish lacking Daw1, I showed that this fiber also assembles in response to a delayed cilia motility cue. The expression of the Urotensin-like peptides, Urp1 and Urp2, is increased as a result of cilia motility in the central canal. By generating mutants lacking both peptides, I showed that these peptides are dispensable for early body morphogenesis, but critical for the maintenance of spinal straightness in adulthood. This work revealed new components of spinal morphology that could be playing roles in human scoliosis. Lastly, in Chapter IV I investigated the mechanism stops further morphogenetic tissue movements once a linear body axis is generated. This occurs in embryos lacking Pkd2, a calcium ion channel known to play a role in flow sensory pathways. Using epistatic tests, I showed that pkd2 acts in a pathway independent of cilia motility and fluid flow to prevent axis over-straightening. Collectively, this dissertation advances our understanding of the role of cilia motility, fluid flow, and downstream factors in body axis straightening and the maintenance of spinal straightness. This work contains both unpublished and published co-authored materials.
Open Access
The Social Brain of Zebrafish
(University of Oregon, 2020-02-27) Stednitz, Sarah; Washbourne, Philip
Social behavior is arguably one of the most complex forms of behavior exhibited by animals. It requires active attention to dynamic multisnsory cues, recall of past experiences, and the generation of situationally appropriate responses. Given the swath of different cognitive systems required, it is unsurprising that social behavior is disrupted in many neurological disorders. Autism spectrum disorders (ASD) are particularly notable, as social impairment is a required diagnostic criteria. Efforts using animal models to both understand the etiology and improve behavioral outcomes for human ASD patients are complicated by the difficulty of replicating the genetic environmental causes. Similarly, measuring deficits in complex behaviors like social interaction is challenging and their neuroanatomical correlates are not yet fully described. To address these issues, I utilized the highly social and genetically tractable zebrafish (Danio rerio) as a model system. I developed a novel assay that shows social engagement requires a behavioral visual stimulus provided by another socially-engaged fish. I demonstrated that both pharmacological manipulation of dopaminergic systems and ablation of a portion of the ventral telencephalon produce predictable deficits in social behavior. Our results also provide evidence that an as yet uncharacterized population of cholinergic neurons in the ventral forebrain are critical for social interactions in zebrafish. This region corresponds to mammalian forebrain regions implicated in social behavior, suggesting an evolutionarily conserved population of cells may drive social orienting in zebrafish and mammals. Further, I identified the time points in early development when specific social behaviors are first observed, suggesting a progressive acquisition of increasingly complex social behaviors over a rapid timescale. This highly variable and early stage in development represents an opportunity to further understand how genetic and environmental factors affect the assembly of the neural circuits underlying complex behaviors.

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Browsing University Archives by Subject "zebrafish"

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