Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (19 results)

  • Article
  • Peer Reviewed
UC Merced Previously Published Works (2018)
Prokaryotic viruses, or bacteriophages, are viruses that infect bacteria and archaea. These viruses have been known to associate with host systems for decades, yet only recently have their influence on the regulation of host-associated bacteria been appreciated. These studies have been conducted in many host systems, from the base of animal life in the Cnidarian phylum to mammals. These prokaryotic viruses are useful for regulating the number of bacteria in a host ecosystem and for regulating the strains of bacteria useful for the microbiome. These viruses are likely selected by the host to maintain bacterial populations. Viral metagenomics allows researchers to profile the communities of viruses associating with animal hosts, and importantly helps to determine the functional role these viruses play. Further, viral metagenomics show the sphere of viral involvement in gene flow and gene shuffling in an ever-changing host environment. The influence of prokaryotic viruses could, therefore, have a clear impact on host health.
    Cover page: Host-Associated Bacteriophage Isolation and Preparation for Viral Metagenomics
    • Article
    • Peer Reviewed
    UC Merced Previously Published Works (2017)
    Animals live in symbiosis with the microorganisms surrounding them. This symbiosis is necessary for animal health, as a symbiotic breakdown can lead to a disease state. The functional symbiosis between the host, and associated prokaryotes, eukaryotes, and viruses in the context of an environment is the holobiont. Deciphering these holobiont associations has proven to be both difficult and controversial. In particular, holobiont association with viruses has been of debate even though these interactions have been occurring since cellular life began. The controversy stems from the idea that all viruses are parasitic, yet their associations can also be beneficial. To determine viral involvement within the holobiont, it is necessary to identify and elucidate the function of viral populations in symbiosis with the host. Viral metagenome analyses identify the communities of eukaryotic and prokaryotic viruses that functionally associate within a holobiont. Similarly, analyses of the host in response to viral presence determine how these interactions are maintained. Combined analyses reveal how viruses interact within the holobiont and how viral symbiotic cooperation occurs. To understand how the holobiont serves as a functional unit, one must consider viruses as an integral part of disease, development, and evolution.
      Cover page: The Intra-Dependence of Viruses and the Holobiont
      • Thesis
      • Peer Reviewed
      UC San Diego Electronic Theses and Dissertations (2008)
      The Tec family non-receptor tyrosine kinase, Interleukin-2 Inducible Tyrosine Kinase (Itk), is an enigmatic enzyme that plays a key role in T cell receptor (TCR)-initiated signaling. In a kinase-dependent fashion, Itk directly and significantly affects the regulation of Phospholipase C gamma-1 (PLC[gamma]1) and the consequent mobilization of Ca²⁺. In a kinase-independent manner, Itk indirectly and significantly participates in the regulation of T cell cytoskeletal reorganization necessary to generate a productive T cell response. However, neither of these Itk functions lead to the complete activation of a T cell. Rather, Itk serves as an important mediator of T cell signals, enabling a tempered response to antigen necessary for the development and differentiation of a naïve T cell. The following dissertation includes a review of the scientific literature covering Itk, the characterization of the Itk protein domains necessary for its activation and localization through TCR engagement, the involvement of Itk in the modification of actin-mediated events emanating from the TCR, the discovery of a soluble ligand affecting Itk recruitment, and the development of an inhibitor specific for Itk activity. The collective incorporation of the data presented herein provides evidence that Itk serves as a modulator, or rheostat, critically fine-tuning the T cell response to antigen
        Cover page: Controlling T lymphocyte activation with a molecular rheostat
        • Article
        • Peer Reviewed
        UC Merced Previously Published Works (2015)
        While largely studied because of their harmful effects on human health, there is growing appreciation that viruses are also important members of the animal holobiont. This review highlights recent findings on viruses associated with Hydra and related Cnidaria. These early evolutionary diverging animals not only select their bacterial communities but also select for viral communities in a species-specific manner. The majority of the viruses associating with these animals are bacteriophages. We demonstrate that the animal host and its virome have evolved into a homeostatic, symbiotic relationship and propose that viruses are an important part of the Hydra holobiont by controlling the species-specific microbiome. We conclude that beneficial virus-bacterial-host interactions should be considered as an integral part of animal development and evolution.
          Cover page: Microbial ecology in Hydra: Why viruses matter
          • Thesis
          • Peer Reviewed
          UC Merced Electronic Theses and Dissertations (2024)

          RNA viruses are ubiquitous across diverse environmental ecosystems and are associated with a wide array of eukaryotic hosts. Ranging from their essential role in biogeochemical cycling to their pathogenic implications in causing animal and plant diseases, extensive insight into the RNA virome has been developed in association with eukaryotic supergroups Opisthokonta and Chloroplastida. Considering the diversity that spans the eukaryotic Tree of Life, animals, plants, and fungi capture only a small proportion of diversity otherwise characterized by unicellular eukaryotes. In this dissertation, studies expand the known diversity of protist-associated RNA viruses, and provide atomistic insight into the binding dynamics that constitute the effort to prevent early HIV-1 infection.

          Chapter 1 provides a review on the ubiquity of environmental protists, RNA viruses, and their interplay across diverse ecosystems. This work aims to highlight the current strategies and efforts to broaden understanding of the protist-associated RNA virome, and provide perspective as to future developments. The article puts into perspective the global distribution of unicellular eukaryotes and their diverse roles spanning from biogeochemical cycling to sustaining marine species biodiversity. This review highlights advancements in Next-Generation Sequencing (NGS) technologies, open-source bioinformatic programs, and provides perspective on how these tools will contribute to expansion of the global RNA virome.

          Chapter 2 explores the abundance and roles of environmental Riboviria associated with unicellular eukaryotic hosts. Based on 302 metatranscriptomes derived from soil and fresh-water protists (amoeba, ciliates, foraminifera, and euglenoids), discovery of novel RNA viruses was performed based on detection of the RNA-dependent RNA polymerase (RdRp) hallmark gene. This study applied a bioinformatic strategy which included identification of viral genomes using geNomad, detection of RdRp-encoding viruses using profile hidden Markov models (HMM), and maximum-likelihood phylogenetic tree construction. While results confirmed the presence of protist-associated Riboviria, analysis of newly identified members were not indicative of general auxiliary metabolic function. Instead, RNA viruses were largely associated with functions related to viral replication.

          Chapter 3 explores the efficacy of the antiviral lectin Griffithsin against early HIV infection. Based on the crystal structure of Griffithsin complexed with mannose glycans (PDB: 2GUD), classical molecular dynamics (MD) was applied to investigate the impact of mutating conserved residues within Griffithsin’s carbohydrate binding sites. Assessment of induced mutations were performed using programs such as Groningen Machine for Chemical Simulations (GROMACS),PyMOL, Avogadro, and Automated Topology Builder (ATB). Results reflected the delocalization of bound mannose glycans in mutant isoforms and validated MD as a robust method to study protein-ligand binding dynamics.

            • Article
            • Peer Reviewed
            UC Merced Previously Published Works (2019)
            The 2018 Cnidarian Model Systems Meeting (Cnidofest) was held September 6-9th at the University of Florida Whitney Laboratory for Marine Bioscience in St. Augustine, FL. Cnidofest 2018, which built upon the momentum of Hydroidfest 2016, brought together research communities working on a broad spectrum of cnidarian organisms from North America and around the world. Meeting talks covered diverse aspects of cnidarian biology, with sessions focused on genomics, development, neurobiology, immunology, symbiosis, ecology, and evolution. In addition to interesting biology, Cnidofest also emphasized the advancement of modern research techniques. Invited technology speakers showcased the power of microfluidics and single-cell transcriptomics and demonstrated their application in cnidarian models. In this report, we provide an overview of the exciting research that was presented at the meeting and discuss opportunities for future research.
              Cover page: Cnidofest 2018: the future is bright for cnidarian research.
              • Article
              • Peer Reviewed
              UC Merced Previously Published Works (2017)
              The last common metazoan ancestor (LCMA) emerged over half a billion years ago. These complex metazoans provided newly available niche space for viruses and microbes. Modern day contemporaries, such as cnidarians, suggest that the LCMA consisted of two cell layers: a basal endoderm and a mucus-secreting ectoderm, which formed a surface mucus layer (SML). Here we propose a model for the origin of metazoan immunity based on external and internal microbial selection mechanisms. In this model, the SML concentrated bacteria and their associated viruses (phage) through physical dynamics (that is, the slower flow fields near a diffusive boundary layer), which selected for mucin-binding capabilities. The concentration of phage within the SML provided the LCMA with an external microbial selective described by the bacteriophage adherence to mucus (BAM) model. In the BAM model, phage adhere to mucus protecting the metazoan host against invading, potentially pathogenic bacteria. The same fluid dynamics that concentrated phage and bacteria in the SML also concentrated eukaryotic viruses. As eukaryotic viruses competed for host intracellular niche space, those viruses that provided the LCMA with immune protection were maintained. If a resident virus became pathogenic or if a non-beneficial infection occurred, we propose that tumor necrosis factor (TNF)-mediated programmed cell death, as well as other apoptosis mechanisms, were utilized to remove virally infected cells. The ubiquity of the mucosal environment across metazoan phyla suggest that both BAM and TNF-induced apoptosis emerged during the Precambrian era and continue to drive the evolution of metazoan immunity.
                Cover page: Viruses and the origin of microbiome selection and immunity
                • Article
                • Peer Reviewed
                UC Merced Previously Published Works (2017)
                  Cover page: Hydroidfest 2016: celebrating a renaissance in hydrozoan research
                  • Article
                  • Peer Reviewed
                  UC Merced Previously Published Works (2021)
                  In recent years, our understanding of the importance of microorganisms on and within our bodies has been revolutionized by the ability to characterize entire microbial communities. No more so is this true than in cases of disease. Community studies have revealed strong associations between microbial populations and disease states where such concomitance was previously absent from aetiology: including in cancers. The study of viruses, in particular, has benefited from the development of new community profiling techniques and we are now realising that their prominence within our physiology is nearly as broad as the diversity of the organisms themselves. Here, we examine the relationship between viruses and colorectal cancer (CRC), the leading cause of gastrointestinal cancer-related death worldwide. In CRC, viruses have been suggested to be involved in oncogenesis both directly, through infection of our cells, and indirectly, through modulating the composition of bacterial communities. Interestingly though, these characteristics have also led to their examination from another perspective-as options for treatment. Advances in our understanding of molecular and viral biology have caused many to look at viruses as potential modular biotherapeutics, where deleterious characteristics can be tamed and desirable characteristics exploited. In this article, we will explore both of these perspectives, covering how viral infections and involvement in microbiome dynamics may contribute to CRC, and examine ways in which viruses themselves could be harnessed to treat the very condition their contemporaries may have had a hand in creating.
                    Cover page: The Viral Janus: Viruses as Aetiological Agents and Treatment Options in Colorectal Cancer
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2017)
                    Hydroidfest 2016 took place on September 23-25 at the UC Davis Bodega Marine Laboratory in Bodega Bay, CA. The meeting brought together cnidarian researchers, with an emphasis on those studying hydrozoans, from North America and other parts of the world. The scientific topics discussed were diverse, including sessions focused on development, regeneration, aging, immunology, symbiosis, and neurobiology. Thanks to the application of modern biological technologies, hydrozoans and other cnidarians are now fertile ground for research in numerous disciplines. Moreover, their amenability to comparative approaches is a powerful asset that was repeatedly showcased during the meeting. Here, we give a brief account of the work that was presented and the opportunities that emerged from the ensuing discussions.
                      Cover page: Hydroidfest 2016: celebrating a renaissance in hydrozoan research.Creative Commons 'BY' version 4.0 license
                      Top