Document Type

Honors Thesis

Publication Date

Spring 5-2016

Abstract

The SHIP1 gene is a member of the inositol polyphosphate-5-phosphate (INPP5) and its expressed protein functions as a negative regulator of myeloid cell proliferation, survival, and migration. Mutations in this gene are associated with various defects and cancers of the immune system. Previous studies have shown that in response to wound formation, ship1-deficient zebrafish have increased neutrophil motility while overexpression of ship1 resulted in decreased neutrophil migration (Lam et al. 2012). From this research, it is suggested that SHIP1 is a key brake that limits neutrophil motility through a PI3K signaling-dependent pathway. While the role of SHIP1 during a wound response has been categorized, its function during a viral infection has been left uncharacterized. The goal of this present study is to examine the role of ship1 during an innate immune response to an influenza infection.

Using the zebrafish, Danio rerio, as an in vivo model organism, we hope to reveal the role of SHIP1 in the innate immune response to a viral infection. It was initially discovered that upon viral infection, SHIP1 is upregulated, promoting further research into the role of SHIP1 in the antiviral innate immune response. Morpholino-mediated SHIP1 knockdown resulted in increased zebrafish survival upon influenza infection, suggesting that SHIP1 is a critical part of the antiviral immune response. Furthermore, SHIP1-KD in zebrafish exhibited decreased production of ROS, indicating that SHIP1 plays a role in pathogen killing.

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