Phone:
(207) 581-2803
Email/web:
carolkim@maine.edu
Address:
University of Maine
Department of Molecular and Biomedical Sciences
Orono, ME
04469
Ph.D. Cornell University
Zebrafish as a Model for Infectious Disease: Throughout history infectious diseases have played a major role in the human condition worldwide. Pathogens also have tremendous environmental and economic impact in agriculture and aquaculture. To counter these agents, vaccines, antibiotics, and new intervention strategies are continually being developed. Although these methods have largely proven to be effective as we have sought to keep pace with microbial adaptation and environment-triggered emergence of new diseases, investigation into alternative methods for controlling infectious disease is clearly warranted.
Through our disease studies with zebrafish, we hope to better understand the myriad immune factors that augment, extend, and prolong the immune response to infection. In order to develop more effective vaccines and to understand host response to pathogens, an infectious disease model is essential. In our studies, zebrafish are exposed to bacterial and viral pathogens that are known to cause disease in other fish species that live in similar environments (e.g. temperature, freshwater vs. marine). Once we have identified the bacteria or viruses that cause disease in the zebrafish, we can study host responses to infection and devise methods to boost host immune response.
Characterization of Zebrafish Toll Signal Transduction Pathway: Recent recognition of the intrinsic importance of the innate immune response, in addition to its regulatory role in subsequent adaptive immunity, suggests that this system plays a crucial role in protection against agents of infectious disease. Our goal is to better understand the innate immune response through the Toll signal transduction pathway. Evidence suggests the existence of Toll receptors, described as "pattern recognition receptors," with the ability to detect a variety of indicators of infectious organisms, and which feed into a common activation pathway. Activation of either the invertebrate or vertebrate signaling pathways results in a cascade of events that leads to the subsequent translocation of a transcription factor (Dorsal or NF-kb, respectively) into the nucleus and regulates synthesis of either antimicrobial/antifungal peptides or cytokines. Through molecular dissection of this pathway in the zebrafish, a vertebrate with a less complex immune system than that of mammals, we seek to identify factors that influence regulation of the innate immune response as well as its role in regulating the adaptive immune response. Ultimately, we hope to learn enough about the Toll signaling pathway to begin to develop methods for intervention that can be applied to mammals and other fish species.
Environmental Toxicants and the Immune System: We recently have become interested in the effects of environmental toxicants, such as arsenic, on the host’s ability to fight infection. In our initial studies, zebrafish were exposed to relatively high levels (50 and 100 uM) of arsenic and have shown that these levels severely compromise the host’s ability to mount an appropriate antiviral immune response. We have continued these studies with very low levels (2 and 10 ppb) of arsenic – levels that are considered safe in drinking water. In these studies, the overall innate immune response was dramatically dampened and the zebrafish were unable to contain and combat either bacterial or viral infection.
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