Characterizing the biochemical and toxicological effects of nanosilver in vivo using zebrafish (Danio rerio) and in vitro using rainbow trout (Oncorhynchus mykiss) by Andrey Massarsky

Thesis submitted to the Faculty of Graduate and Postdoctoral Studies University of Ottawa In partial fulfillment of the requirements for the PhD degree in the Ottawa-Carleton Institute of Biology

Thèse soumise à la Faculté des Études Supérieurs et Postdoctorales Université d’Ottawa En vue de la réalisation partielle du doctorat à L’Institut de Biologie Ottawa-Carleton

©Andrey Massarsky, Ottawa, Canada, 2014

This dissertation is dedicated in loving memory of my grandmother Valentina Tulina. I am eternally grateful for her efforts to ensure my academic success from the first day I started school. I have no doubt that she is smiling from up above as I acquire my PhD.

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Acknowledgments It is hard to believe that five years of graduate studies have passed by so quickly. There are many people, whom I would like to thank from the bottom of my heart for everything they have done for me throughout my journey as a graduate student. First and foremost I would like to thank my supervisor Dr. Thomas W. Moon for ever so patiently instilling in me the love for scientific research. His outstanding guidance and mentoring throughout the years have not only opened my eyes to the vast research tools, but also dramatically improved my abilities to think critically and write and present scientific knowledge. My accomplishments would have been impossible without Dr. Moon, and for this I will forever be indebted to him. Secondly, I would like to express my sincere gratitude to my co-supervisor Dr. Vance L. Trudeau, who despite having multiple students in his own lab, always found the time to inquire about my progress and make valuable suggestions pertaining to my experiments. Dr. Trudeau also played a pivotal role in reviewing all of my manuscripts, often pointing out things that were missed by other editors, thus ensuring the high quality of the final product. Furthermore, I would like to extend my thanks to my committee members: Drs. Jules Blais, William Willmore, and Paul White, for stimulating discussions that helped to shape this thesis into an interesting narrative. I would also like to recognize the input of many collaborators and colleagues, including Dr. Chris Metcalfe, Dr. Greg Goss, Dr. Azam Tayabali, Kathy Nguyen, and Dr. Antoine Morin. Special thanks also go to Bill Fletcher and Vishal Saxena for taking excellent care of the fish facility and ensuring that my experiments ran as smoothly as possible.

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I would like to express my gratitude to the Department of Biology personnel. Dr. John Basso always had a great advice when I was in doubt, including his recommendation to pursue an Honors project with Dr. Moon. Moreover, my numerous teaching assistantships with Dr. Basso have not only taught me a great deal of microbiology and molecular biology techniques, but also improved my skills to instruct undergraduate students. Lise Belanger and Yves Genest helped tremendously with the organization of my mini-courses, which were my summer highlights for the past three years. Finally, Doreen Smith, Isabelle Morissette, and Gita Kangas booked my numerous committee meetings and processed a myriad of documents and contracts. I would also like to acknowledge my labmates over the past five years, who shaped my PhD studies into an unforgettable adventure. These include Dr. Shahram Eisa-Beygi, Aziz Al-Habsi, Dr. Paul M. Craig, Kim Mitchell, Marilyn Vera Chang, Rand Pasha, Pamela Stroud, and Rance Nault. I was also fortunate to supervise very talented undergraduate students: Lisa Dupuis, Jessica Taylor, Ren Abraham, Laura Strek, and Justine Labarre, who contributed to the progress of my research. Finally, I would like to thank my family: my parents Elena and Michael, for their spiritual and generous financial support during my studies; my brother Alexey, for all the encouragement and great stress-relieving squash matches; my grandparents Lyudmila and Rudolf, who showed a lot of support from Germany; my in laws Pier and Letty, for their support and great company on Friday-gym evenings. Lastly, I would like thank my beautiful wife Cintia for putting up with my workaholic tendencies for the past five years and comforting me on the days when everything seemed hopeless.

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Abstract Many consumer and medical products contain engineered nanomaterials (ENMs) due to their unique properties arising from their small size of