Date of Award

5-2015

Level of Access

Campus-Only Thesis

Degree Name

Master of Science (MS)

Department

Microbiology

Advisor

Robert T. Wheeler

Second Committee Member

Carol H. Kim

Third Committee Member

John T. Singer

Abstract

Candida spp. are opportunistic commensal gastrointestinal and mucosal pathogens commonly found in patients undergoing radiation therapy. There are few studies that explore the mechanisms by which patients undergoing radiation treatment become increasingly susceptible to Candida. This study utilizes the transparency of the larval zebrafish to explore the dynamics between radiation and infection in a live host. My work reveals that radiation-enhanced susceptibility to candidemia in this model is associated with an overall decrease in both neutrophils and macrophages. Radiation induces high levels of tp53- dependent apoptosis, which may account for the alteration in innate immune cell homeostasis. This phylogenetically conserved tp53 dependent apoptosis pathway appears to utilize caspase 3, and may also involve caspase 8. Expression of both casp3 and casp8 was increased by radiation, as seen by immunostaining or global gene expression analysis and qPCR respectively. The unique advantages of the larval zebrafish model enabled these combined studies on irradiation and infection in the zebrafish that provide insight into how irradiation affects immune gene regulation, immune cell homeostasis, and infection susceptibility.

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