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IRF4 Does the Balancing Act: a Dissertation University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2015-01-07 IRF4 Does the Balancing Act: A Dissertation Ribhu Nayar University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Cellular and Molecular Physiology Commons, Immunity Commons, and the Immunology of Infectious Disease Commons Repository Citation Nayar R. (2015). IRF4 Does the Balancing Act: A Dissertation. GSBS Dissertations and Theses. https://doi.org/10.13028/M2302T. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/746 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. IRF4 DOES THE BALANCING ACT A Dissertation Presented By RIBHU NAYAR Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY JANUARY 7, 2015 PROGRAM IN IMMUNOLOGY AND VIROLOGY IRF4 DOES THE BALANCING ACT A Dissertation Presented By RIBHU NAYAR The signatures of the Dissertation Defense Committee signify completion and approval as to style and content of the Dissertation Leslie J. Berg, Ph.D., Thesis Advisor Susan L. Swain, Ph.D., Member of Committee Eric. S. Huseby, Ph.D, Member of Committee Michael A. Brehm, Ph.D, Member of Committee Christine A. Biron, Ph.D, Member of Committee The signature of the Chair of the Committee signifies that the written dissertation meets the requirements of the Dissertation Committee Joonsoo Kang, Ph.D, Chair of Committee The signature of the Dean of the Graduate School of Biomedical Sciences signifies that the student has met all graduation requirements of the school. Anthony Carruthers, Ph.D., Dean of the Graduate School of Biomedical Sciences Program in Immunology and Virology January 7, 2015 Dedication This thesis is dedicated to my family. Without their support this journey would have never started. iii Acknowledgements I came to graduate school not to get to a degree; I came here to become a scientist. It is said that the thrill is in the journey, not in the destination. With graduate school, my journey has just started. Many people have participated in my journey, and I take this opportunity to thank them for their unending guidance, support and love, without which I would have never reached this far. “Guru govind dono khade, kaake lagu paaye, Balihari guru aapno, govind diyo bataye” - Kabir Translation - “Guru and God both are here, to whom should I first bow? All glory be unto the guru, path to God who did bestow” I would like to thank foremost, my mentor Dr. Leslie Berg. Leslie is a great scientist, a leader and a mentor. She has always made time to discuss science, plan experiments, encouraged me to think independently and above all interpret data un-biasedly. Most importantly, she put a lot of faith in me and was patient when things did not work for many years; a time during which even I lost faith in myself, but she was undeterred. She once told me that there are three types of experiments - type I gives you a novel biologically relevant outcome, no matter what the result is. With type II experiments you shall learn something about iv biology if they give a certain type of result. While type III experiments are just a re-affirmation of the facts already known. She told me to succeed I must always aim for the type I experiments. She is also a great role model for me in my personal life. She has set a great example of a strong female leader, and demonstrated to me how to establish ones identity. I shall carry forward with me her training, and I hope I shall never forget the life-lessons she has taught me. Someone once told me that you start college as young girls and finish as young ladies. I think my growth was largely stunted till I met Regina Whitehead. She may be the lab manager for everyone else, but to me she has always been my lab mom. She has counseled me at every step, personal or professional. When times were dark, she always showed me the ray of hope. But when I faltered, she helped me see my follies and fix them. I am so much more of a complete person than what I was when I started grad school. No wonder she is my lab mom! Thank you Regina! And as always, what would I do without you? I would also like to thank Amanda Prince, with whom I worked when I first joined the Berg lab. She is an amazing person and a great colleague. After I joined the lab, I started working with Hyun-Mu Shin, a post doc in our lab. He is also a great scientist and epitomizes that nothing is impossible if you really put your heart into it. I would also like to thank Megan Enos, a post-doc in our lab. I would always go up to her with questions, and I think I drove her crazy when I v was qualifying. Right before my qualifying exam, I walked up to her and said “OK Megan, last question for you”. She looked at me amusingly, and I corrected myself “last question, before the exam”. John Evans, Catherine Yin and Wen- Fang Wu also made the Berg lab a very happy place to be. John was also my go to person for all flow queries. The present members of the Berg lab make this an intellectually very stimulating environment to be in. I think I am very fortunate to have Elizabeth Schutten in the lab. She is a very hardworking and sincere student, and has been a great collaborator and a friend. She had also contributed immensely to the LCMV Clone 13 project described in Chapter V. Without her help, harvesting multiple organs from 20 or more mice at a time, doing 100 plate plaque assays and running on flow cytometer for some 16 hours would not have been fun. James Conley is also a great lab mate. He is really mature and usually laughs at Beth and I. I think we are mentally under-developed for him. But nonetheless, I love discussing project ideas with him and really admire this scientific acuity. It’s really fun to be around Hyoung-Soo Cho and Yves Falanga, and they too add a lot of flavor to our lab. A special thank you to Sharlene Hubbard who maintains our mouse colony. She is a great lab member. She has helped me keep records of the numerous lines of mice I have bred, assisted me with genotyping, sacrificing and making breeders. If she wasn’t in the mouse room looking out for me, I would not have been half as productive, as I have been so far. vi I would also like to thank other members of our department. Laurie Kenney, a senior student is a great friend of mine. She once told me “the point of an experiment is to get maximum useful information out”. That’s when I started thinking more critically about my LCMV experiments and as to what all information can be gathered without compromising the quality of the data. I would also like to thank Stephen Waggoner who helped me get started with the LCMV experiments, and was my go to person for all questions, no matter what time of the day or night it was. Steve also inspired me to work hard, read and showed to me that getting a faculty position was not impossible! Brian Stadinski is another great role model. He is extremely focused, dedicated and hardworking. I have learnt a lot from him and he is my late night and Friday evening go to buddy! I would also like to thank Dave Moquin and Kenta Moriwaki. They are great friends, and I would sometimes join them for their Friday night beer session in the break room. Its great to have Stina Urban and Bianca Bautista in our department, both have helped me in my projects, and I have had many wonderful discussions with them. I would also like to thank members of the Kang lab - Nitya Jain, Kavitha Narayan, Nidhi Malhotra, Katelyn Sylvia and Bing Miu. The Kang lab is such a great neighbor, and our go to place for antibodies and reagents. Nitya and Kavitha are one of the most hardworking and intelligent students I have known. They have inspired me to not give up in grad school, and shown to me that if you vii work hard enough, you shall succeed in the end. Katelyn and Bing are my coffee and chat buddies. This acknowledgement would be incomplete without thanking members of my TRAC committee. Ray Welsh, who is also my chair, has mentored me on my LCMV projects. I would just walk into his office and he always made time for me. Mike Brehm was also my go to person for all LCMV questions. I have spammed his inbox many times with my data, and he has always patiently responded to all my queries. Joonsoo Kang has always encouraged me to think a step beyond the obvious. What I liked most about talking to him was that he never gave me an answer, rather he always lead me to it. Of course all this happened before 6 PM, after which the conversations were always more philosophical than scientific.
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