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Open Access Publications from the University of California

Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC Santa Cruz Electronic Theses and Dissertations (2023)

The circadian clock is a cell autonomous clock that drives the daily rhythms of biological processes. Emerging literature shows a clear relationship between the circadian clock and the immune system, but the mechanisms behind this relationship are not well understood. Due to their genetic tractability and similarity to humans, zebrafish (Danio rerio) are an appealing model to study the connection between the clock and immunity. However, no studies have investigated how bacterial exposure affects the clock in this model organism. In this thesis, we show that heat killed (HK) Streptococcus pneumoniae (Spn) and Escherichia coli augment the expression of the light driven genes, per2 and cry1a, in zebrafish cells. Further investigation into the mechanism by which HK Spn alters circadian gene expression revealed that inhibition of reactive oxygen species (ROS) abolishes the response to HK Spn exposure, indicating an ROS dependent mechanism of per2 and cry1a augmentation by HK Spn. In addition to investing how zebrafish cells respond to bacteria, we also generated circadian reporter fish and tested how these reporters respond to bacteria. We found that the reporters behaved as previously reported in the literature in different lighting conditions, but that Spn infection did not alter their circadian rhythms. Together, these results illustrate how multiple environmental signals can converge via a common pathway to induce changes in circadian gene expression in zebrafish cells, and how live circadian zebrafish reporters can be used to study the circadian response to bacteria.

    • Article
    • Peer Reviewed
    UC Santa Cruz Previously Published Works (2022)
    Circadian clocks are universally used to coordinate biological processes with the Earth's 24-h solar day and are critical for the health and environmental success of an organism. Circadian rhythms in eukaryotes are driven by a cell-intrinsic transcription-translation feedback loop that controls daily oscillations in gene expression which regulate diverse physiological functions. Substantial evidence now exists demonstrating that immune activation and inflammatory responses during infection are under circadian control, however, the cellular mechanisms responsible for this are not well understood. The zebrafish (Danio rerio) is a powerful model organism to study vertebrate circadian biology and immune function. Zebrafish contain homologs of mammalian circadian clock genes which, to our current knowledge, function similarly to impart timekeeping ability. Consistent with studies in mammalian models, several studies in fish have now demonstrated a bidirectional relationship between the circadian clock and inflammation: the circadian clock regulates immune activity, and inflammation can alter circadian rhythms. This review summarizes our current understanding of the molecular mechanisms of the zebrafish clock and the bi-directional relationship between the circadian clock and inflammation in fish.
      Cover page: Immunity, Infection, and the Zebrafish Clock
      • Article
      • Peer Reviewed
      UC Santa Cruz Previously Published Works (2024)
      The circadian clock is a cell-autonomous process that regulates daily internal rhythms by interacting with environmental signals. Reports across species show that infection can alter the expression of circadian genes; however, in teleosts, these effects are influenced by light exposure. Currently, no reports analyze the direct effects of bacterial exposure on the zebrafish clock. Using zebrafish Z3 cells, we demonstrate that exposure to heat-killed Streptococcus pneumoniae (HK-Spn) augments the expression of core repressive factors in a light- and time-dependent manner. In constant darkness, HK-Spn highly upregulated cry1a, per3, and per1b expression. In the presence of light, HK-Spn exposure rapidly and strongly upregulated per2 and cry1a, and this was proportionally increased with light intensity. The combinatorial effect of light and HK-Spn on per2 and cry1a was not duplicated with H2O2, a known byproduct of light exposure. However, the ROS inhibitor N-acetyl cysteine was sufficient to block HK-Spn augmentation of per2, cry1a, and per3. These findings demonstrate that exposure to an inactive bacteria influences the expression of zebrafish clock genes under different light conditions.
        Cover page: Heat-inactivated Streptococcus pneumoniae augments circadian clock gene expression in zebrafish cells.
        • Article
        • Peer Reviewed
        UC Santa Cruz Previously Published Works (2022)
        Project-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources to facilitate effective project-based coursework for students. We have developed a framework for facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host an experiment for many students around the world simultaneously. Experiments on this platform can be run on long timescales and with materials that are typically unavailable to high school classrooms. This allows students to perform novel research projects rather than just repeating standard classroom experiments. To investigate the impact of this program, we designed and ran six user studies with students worldwide. All experiments were hosted in Santa Cruz and San Francisco, California, with observations and decisions made remotely by the students using their personal computers and cellphones. In surveys gathered after the experiments, students reported increased excitement for science and a greater desire to pursue a career in STEM. This framework represents a novel, scalable, and effective PBL approach that has the potential to democratize biology and STEM education around the world.
          Cover page: Cloud-controlled microscopy enables remote project-based biology education in underserved Latinx communities
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