Date of Award

8-2010

Level of Access Assigned by Author

Campus-Only Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry

Advisor

Carol H. Kim

Second Committee Member

Robert E. Gundersen

Third Committee Member

Charles Moody

Abstract

[Description from paper's Discussion, pp 50-53] ...The zebrafish is becoming a well established model for studying not only development but also immunity. Drosophila has been used as a model for studying all aspects of science including development and immunity, however, its evolutionary 50 divergence from mammals has made transitions of findings into mouse and human models difficult. On the other hand, although the mouse model is well suited for molecular studies pertinent to human disease, cost and low breeding numbers have put restraints on the usability of mice. The zebrafish encompasses the benefits of both model systems in that cost is low, breeding cycles and number of offspring is high, and it appears that the zebrafish contain many of the same proteins present in the mammalian system...

...This work presents the first functional data demonstrating the presence of a MDA5-like signaling cascade in zebrafish. Data showing the ability of zMDA5 to recognize rhabdo virus infection suggests a new role for MDA5. It has been suggested that existed prior to RIG-I. It is quite possible that earlier in evolution, MDA5 was involved in the recognition of a wider array of viruses (48). Preliminary data suggest that SHRV has already devised a mechanism to evade MDA5 signaling, reinforcing the notion that zMDA5 plays a role in recognition of SHRV. Further studies of the MDA5 signaling cascade may give new insight into how viruses have evolved to evade immune recognition and how vertebrates have evolved to combat them. The use of the zebrafish model provides us with an evolutionarily more primitive, and theoretically less complex, system which may provide clues as to how the immune system has evolved over time to deal with changes in the environment and pathological communities.

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