Characterizing Neuronal and Cardiac Isoforms of Voltage-Gated CaV1.2 CACNA1C Calcium Channels Kristin Marie Webster B.A., Hamilton College, 2009 Dissertation submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in the Department of Neuroscience at Brown University Providence, RI May 2015 Copyright © by Kristin Marie Webster. All rights reserved. ii This dissertation by Kristin Marie Webster is accepted in its present form by the Department of Neuroscience as satisfying the dissertation requirements for the Degree of Doctor of Philosophy. Date ___________ ________________________ Diane Lipscombe, Advisor Neuroscience Department Brown University Recommended to the Graduate Council Date ___________ ________________________ Anne Hart, Reader Neuroscience Department Brown University Date ___________ ________________________ Eric Morrow, Reader Molecular Cell Biology & Biochemistry Department Brown University Date ___________ ________________________ Anjali Rajadhyaksha, Reader Pediatrics Department Weil Cornell College of Medicine Approved by the Graduate Council Date ___________ ________________________ Peter Weber Dean of the Graduate School Brown University iii Kristin M. Webster Born July 29th, 1987 Princeton, NJ Brown University Residence Box GL-N, Neuroscience Graduate Program 153 Governor St Unit 2 Providence, RI 02912 USA Providence, RI 02906 USA Phone: +1 (401) 863-2615 Phone: +1 (570) 575-3651 Email: [email protected] Email: [email protected] EDUCATION Brown University Providence, RI PhD candidate in Neuroscience 2009 - Present Advisor: Professor Diane Lipscombe, PhD Hamilton College Clinton, NY BA, magna cum laude, Neuroscience, Phi Beta Kappa 2009 FELLOWSHIPS Ruth L. Kirschstein National Research Service Award from the NIMH 2012-2014 "Neuronal-Specific Splicing of CaV1.2 L-type Calcium Channels" REFFERRED PUBLICATIONS Ruz, M., Moser, A., & Webster, K. (2011). Social Expectations Bias Decision-Making in Uncertain Inter-Personal Situations. PLoS ONE. 6(2). RESEARCH TRAINING The Genome Access Course 2011 Two day intensive course at Cold Spring Harbor Laboratories to familiarize participants with online tools for bioinformatics and analysis of genomic data RESEARCH EXPERIENCE Biology Department, Hamilton College 2008-2009 Research Assistant • Examined the role of the insect neurotransmitter octopamine in an olfactory learning paradigm in Drosophila melanogaster larvae • Completed a senior thesis with honors Brain and Cognition Lab, Oxford University Spring 2008 Research Assistant • Ran participants and performed data analysis in an experiment examining the role of social biases in decision making iv Biology Department, Hamilton College Summer 2007 Research Assistant • Conducted experiments on octopamine synthesis and the enzyme tyramine-β-hydroxylase through Western Blot analysis in Apis mellifera Biology Department, Misericordia University Summer 2006 Research Assistant • Tested coatings for glass medical containers INVITED SEMINARS Hamilton College 2013 POSTERS/PRESENTATIONS Webster, K and Lipscombe, D (2014). Different forms of calcium channel CaV1.2 proteins are expressed in brain and heart. Miami 2014 Winter Symposium: The molecular basis of brain disorders. Webster, K and Lipscombe, D (2013). Different forms of calcium channel CaV1.2 proteins are expressed in brain and heart. Society for Neuroscience Annual Meeting. Webster, K and Lipscombe, D (2013). Head vs. Heart: A Physiological Characterization of the Neuronal and Cardiac Isoforms of CaV1.2. Brown University Neuroscience Graduate Program Annual Retreat. Awarded 2nd place. CACNA1C calcium channels: Multiple isoforms expressed in different tissues. Brown University Neuroscience Graduate Program In House Seminar Series (2013). Webster, K and Lipscombe, D (2012). Investigating Nova-2’s Regulation of Alternative Splicing in CaV1.2 pre-mRNA and Neuronal Function. Brown-NIH GPP Retreat. Investigating Nova-2’s Regulation of Alternative Splicing in CaV1.2 pre- mRNA and Neuronal Function. Brown Univ. Neuroscience Graduate Program’s Seminar Series (2012). Webster, K, Andrade, A, and Lipscombe, D (2012). CNS- specific isoforms of the calcium channel CACNA1C gene regulated by Nova2. Society for Neuroscience Annual Meeting. Using Next Generation Sequencing to Investigate Nova-2’s Regulation of Alternative Splicing in CaV1.2 pre-mRNA. Brown Univ. Neuroscience Graduate Program Seminar Series (2011). v TEACHING EXPERIENCE Sheridan Center for Teaching and Learning, Brown University Certificate I: Sheridan Teaching Seminar – Reflective teaching • Program in developing a reflective teaching practice 2010-2011 • Discussion leader 2011-2014 Certificate III: The Professional Development Seminar 2013-2014 • Program in developing a teaching portfolio and preparing for the academic job market • Teaching portfolio includes: teaching philosophy statement, sample syllabus, cover letter, CV, broader impact statement Certificate IV: The Teaching Consultant Program • Learning to provide constructive, cross-disciplinary feedback and analysis as a teaching consultant • Teaching Consultant 2011-2012 • Head Teaching Consultant for the Life and Physical Sciences 2012- 2014 o Leads the Certificate IV training meetings with the Head Teaching Consultant for the Humanities and Social Sciences Faculty Trainer in Peer Observation 2012-2014 • Training faculty from various departments in the scholarship of cross-disciplinary peer observations Neuroscience Department, Brown University Teaching Assistant, Introduction to Neuroscience Fall 2010 • Led weekly recitation sections, graded exams, coordinated final review/fundraising event Psychology Department, Hamilton College Teaching Assistant, Statistical Methods in Psychology 2007-2009 Chemistry Department, Hamilton College Teaching Assistant, Intro to Organic Chemistry Laboratory Course Spring 2010 STUDENT MENTORING Barrett Weiss, undergraduate summer researcher Summer 2013 Sophia Lin, undergraduate senior thesis student Fall 2012-Spring 2013 Rachel Stevenson, rotating graduate student Fall 2012 Patrick O’Hern, rotating graduate student Summer 2012 Natalie Chavez, rotating graduate student Spring 2011 vi AWARDS Graduate Student Travel Award to attend ISSoTL conference 2013 Concentration Honors in Neuroscience, Hamilton College 2009 Elihu Root Fellowship, Hamilton College 2009 • Award to support graduate study Academic Fund for Seniors, Hamilton College 2008 • Award to support senior thesis research The Jeffery Science Fund, Hamilton College 2008 • Summer internship stipend Deans Lists, Hamilton College 2005-2009 Bristol Scholar, Hamilton College 2005-2009 • Half-tuition academic scholarship and research stipend UNIVERSITY SERVICE Graduate Student Representative to the Neuroscience Faculty 2012-2013 Neuroscience Graduate Program Admission Committee 2012-2013 Neuroscience Graduate Program Recruitment Weekend Coordinator 2012-2013 The Sheridan Center for Teaching and Learning Advisory Board 2012-2014 SOCIETIES 2013-Present International Society for the Scholarship of Teaching and Learning 2009-Present Society for Neuroscience 2009-Present Phi Beta Kappa, National Academic Honor Society 2009-Present Sigma Xi, National Scientific Research Society 2007-Present Psi Chi, Psychology National Honor Society vii ACKNOWLEDGEMENTS I would like to acknowledge my wonderful advisor and mentor, Diane Lipscombe. I thank her not only for her incomparable PhD training, but her commitment to mentoring all aspects of my graduate career. I value the time she spent personally teaching me how to do electrophysiology and her vibrant presence in the lab. She cultivates an environment in which it is not only safe to ask questions but exploration and risk taking are encouraged and supported. I appreciate her balance of support and guidance while encouraging my development into an independent scientist. Under her tutelage, I have developed into a stronger experimentalist, writer, mentor, and communicator. I am thankful to the past and present members of the Lipscombe lab including Sylvia Denome, Arturo Andrade, Summer Allen, Daniel DuBreuil, Erin Hoops, Cecilia Phillips Toro, Spiro Marangoudakis, Rachel Jiang, and Tom Helton; in addition to being excellent scientists and colleagues, I am thankful to count many of them as close friends who made my time in lab so enjoyable. In particular, I would like to thank Sylvia for patiently answering all of my questions and for sharing her vast knowledge of molecular biology. Tom was the first person I learned electrophysiology from and I have been fortunate to continue a collaboration with his group even after he left the lab. To Spiro- you left behind one of the most detailed experimental protocols I have ever seen and my Western blots benefited enormously. I would also like to thank Kishan Patel and Sophia Lin, two undergraduates who worked on the Western blots included in this dissertation. To my lab ‘big brother and sister’- Arturo and Summer, I owe them more thanks than space permits. They taught and mentored me in almost all of the experimental viii methodologies used in this dissertation and were key players in my graduate school support network. I also thank Dan, who made an excellent statistics guru. To my parents, Don and Laura Webster, I thank them for their unending support and encouragement. I would also like to thank my sister, Kimberly Webster. In addition to being my biggest cheerleader, hers were the first neurons that I ever thought about. Finally, I would like to thank