UC Santa Cruz

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.