University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2020 The role of extracellular proteases, matrix metalloproteinase-2 and -9, in regulating the mammalian circadian clock Kathryn Halter University of Tennessee, [email protected] Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Recommended Citation Halter, Kathryn, "The role of extracellular proteases, matrix metalloproteinase-2 and -9, in regulating the mammalian circadian clock. " PhD diss., University of Tennessee, 2020. https://trace.tennessee.edu/utk_graddiss/5734 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Kathryn Halter entitled "The role of extracellular proteases, matrix metalloproteinase-2 and -9, in regulating the mammalian circadian clock." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Biochemistry and Cellular and Molecular Biology. Rebecca A. Prosser, Major Professor We have read this dissertation and recommend its acceptance: Jim Hall, Matthew Cooper, Cynthia B. Peterson, Theresa Lee Accepted for the Council: Dixie L. Thompson Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) THE ROLE OF EXTRACELLULAR PROTEASES, MATRIX- METALLOPROTEINASE-2 AND -9 IN REGULATING THE MAMMALIAN CIRCADIAN CLOCK A Dissertation Presented for the Doctor of Philosophy Degree The University of Tennessee, Knoxville Kathryn Abrahamsson Halter May 2020 Copyright © 2019 by Kathryn Abrahamsson Halter. All rights reserved. ii DEDICATION I would like to dedicate this dissertation to all of the strong women that have influenced me. To my kindergarten teacher, Mrs. Lowenstein, for recognizing my intellectual gift and giving my parents extra books for me to read as a child. To my high school volleyball coach, Kerri Morrison, who took me to my first Women in Leadership conference and taught me the value of coaching and mentorship. To my high school physics teacher, Mrs. Jennifer Gottlieb, who showed me the excitement that comes from a mathematical understanding of the rollercoasters. To my high school counselor, Michelle Kosi, who helped me find scholarships to pay for my undergraduate education. To Dr. Kate Teeter, who taught me to critically evaluate scientific literature and be inspired by evolution. To Paula Genovese, an inspirational laboratory instructor and mentor in the importance of volunteering. To Mary Martin, my determined genetics instructor dedicated to her students and getting to the bottom of each of their questions. To Marsha Lucas, my biochemistry laboratory instructor who challenged her students and imparted the necessity of keeping a good laboratory notebook. To the late Dr. Elizabeth Howell, an advocate of scientific ethics, visual communication methods and effective mentorship techniques. To Dean Theresa Lee and Dr. Rebecca Prosser, for forging the way for young women leaders in the fields of circadian rhythms and neuroscience. To Dean Cynthia Peterson, for creating a program for women and minorities to pursue scientific research and for being an example of “the Volunteer spirit”. To Ana Bernal Gomez, who taught me that professionalism can be incorporated to every life aspect. To Abby Trotter, who helped facilitate my introduction to advocating for science and for supporting comradery between academics and entrepreneurs alike. To Sheila Headrick Halter, for her advice and mentorship in navigating male-dominated professions. To Erika Halter, who taught me that successful women offer thoughtful and creative solutions. To my sister, Meagan Abrahamsson, who continues to be a reminder that education can be your passport to the world and that listening to others is the best way to lead. To my godmother, Donna Giannola, who lifts up women with her kindness and laughter. To my aunt, Rosemary Kadrich, who taught me the importance of our actions on the young people that look up to us and for supporting my independence. To my aunt, Loretta Abrahamsson, who has shown me that education is priceless, and persistence can get you anywhere. To my late iii grandmother, Eleanor Giannola, who taught me that a homecooked meal brings people together and heals all wounds. To the next generation of women scientists, including Alyssa Briggs, I hope that your curiosity continues to bring up exciting questions about the world we live in that still need to be answered. Importantly, I dedicate this dissertation to the strongest woman I knew, my mother, the late Tina Abrahamsson. She was the first one to notice that I was observant and curious. She facilitated my siblings and my learning throughout each summer by giving us extra workbooks to complete that were above our grade level. She spent hours in the library with us helping pick out books and late nights making sure we finished school projects. She taught me the importance of independence and gave me the freedom to follow my dreams. Most of all, she taught me that the strength of women lies within their capacity to love, and I am thankful that hers was unlimited. iv ACKNOWLEDGEMENTS Throughout the writing of this dissertation I have received a great deal of support and assistance. I would first like to thank my advisor, Dr. Rebecca Prosser, whose expertise was invaluable in formulating the research topic, methodology, and composition of dissertation in particular. Thank you for pushing my intellectual boundaries and for supporting my project. I would like to thank members of the Program for Excellence and Equity in Research (PEER). The mentoring and financial support I received early on in my graduate education was essential to make it through the first tough years. I also would like to acknowledge the PEER community, including Dr. Seekenia Haynes, for their encouragement and allowing me to mentor younger students as well. I would like to thank Dean Cynthia B. Peterson for introducing me to Dr. Prosser, and to the research opportunities at the University of Tennessee, Knoxville (and its football program). Thank you for seeing something in a young scientist and inspiring me to join the PEER family and the Department of Biochemistry & Cell and Molecular Biology (BCMB). I would like to thank Dean Theresa Lee of the College of Arts and Sciences, Dr. Jim Hall of the BCMB Department and Dr. Matthew Cooper of the Psychology Department for their mentorship, guidance and constructive critiques of my research projects and dissertation. I would like to thank my BCMB colleagues. First my lab members, Dr. Yukihiro Yamada, Dr. Jonathan Lindsay, and Dr. Joanna Cooper; thanks to each of you for your guidance, willingness to help, and to help make sense of my research findings. Thank you to Dr. Andrew Stafford for being our adopted lab member and a great source of support. Thank you to Ana Bernal Gomez for volunteering her time to help keep the BCMB Graduate Student Organization running and for her valuable friendship. Thank you to Debalina Acharyya for bringing a ray of sunshine to work every day. I would like to acknowledge the hard-working undergraduate students that assisted in the completion of many of the v experiments included in this dissertation, including Jessica Grenvik, Sarah Grace Lebovitz, Randy Carpenter, Jessica Bertram, Cynthia Ellis and Catherine Bagby. I would like to acknowledge Dr. Karen Gamble and Dr. Lauren Hablitz, trusted collaborators of our laboratory in the circadian rhythms field. I would like to thank the BCMB and UTK faculty for imparting on me a diversity of knowledge, especially to Dr. Tessa Burch-Smith and Dr. Brad Binder for giving their time and lab space during my laboratory rotations. Many thanks are due to Dr. Maitreyi Das and Dr. Mariano Labrador for allowing me to use their microscopes and for their technical support. I would also like to thank Dr. Keerthi Krishnan and Dr. Billy Lau for teaching me immunohistochemical techniques. I would like to thank Dr. James Fordyce for facilitating many stimulating discussions about statistics, likelihood, and for his extensive knowledge of binomial nomenclature. The BCMB staff (LaShel Brown, Cheryl Hodge and Lori Daniels) for helping support me and resolve a myriad of matters. I would like to thank my undergraduate mentor, Dr. Erich Ottem, for his inspiring lectures on neuroendocrinology, for taking the time to train me in performing “real” research, and for recognizing that I could successfully get through graduate school. I would like to thank my family, especially my brother Cameron Abrahamsson and sister Meagan Abrahamsson, for their heartfelt support and keeping our family foundation a solid part of all of our successes. To my late mother, Tina Abrahamsson and father, Robert Abrahamsson, for supporting my growth as a young woman. Thank you to Sara Briggs, for your support and kindness. Thank you also to the Halter family, as each of you have for lent sympathetic ear and provided priceless advice. Many thanks are deserved by my (mostly) loyal companion, Cubby B. Dog, for collecting the mail for me and spending many late nights curled by my feet while I wrote this dissertation. vi Most importantly, I would like to thank my husband, Mathew Halter, for his unconditional commitment. As my confidant and champion, thank you for helping me rise to the occasion and for reminding me of the greater goal. vii ABSTRACT Molecules existing in the extracellular space (ECS) make up a complicated network of structural proteins, signaling molecules, cellular adhesion molecules and transmembrane receptors. Many ECS molecules are implicated as active regulators of structural and functional brain plasticity.