This preface describes a personal and professional journey studying the molecular biology of brain function and complex behavior. Even with rapid advances in technology, we still don't understand the genetic and environmental interactions that give rise to complex diseases and behavior with small effect size. Approaches that use behavioral genomics or data science methods to answer questions are often criticized for lacking explicit hypotheses and predictions. Neuroscience experiments are criticized for lacking behaviorally relevant manipulations and being too reductionists. Senior scientists everywhere are saying that inadequate computational training is the most significant impediment to scientific advances. For my thesis, I attempted to overcome all of the problems mentioned above in modern biology to identify molecular links between brain and behavior.
The ecosystem surrounding my research was multi-disciplinary and multi-institutional. Because a broad audience my influenced research, I have a strong motivation to write my research for a broad audience. I hope that all my colleagues and future researchers can find a least one thing of use in my body research, whether it be related to a biological phenomena or technical innovation. Before I devolve into the domain-specific details of research and its implications, let me first describe the ecosystem where I worked and thank all the people who have made significant contributions to my growth and development as a scientist.
First and foremost, this thesis would not exist without my graduate supervisor, Dr. Hans Hofmann, who in his eternal optimism, always insisted that 'failures' were successes in one shape or form. Though not technically part of my graduate research, the three years I worked as a lab manager in the Hofmann lab (2009-2012) played a defining role in shaping my brain and my view of the world. Lauren O'Connell was an incredible mentor who taught me numerous molecular protocols and gave great advice that jump-started my academic journey. Misha Matz, Carly Kenkle, and Sarah Davis adopted me into their evolutionary genomics journal club where I discovered some of the analytical methods I still use today. Steve Phelps, Kim Hoke, and Ron Oldfield supported my professional development those early years by writing numerous letters of recommendation for travel awards and fellowships. I'll never forget how many great ideas were sparked during the Friday "Brain, Behavior, and Evolution Seminars" and the "Friday Afternoon Rooftop Socials" which lead to funded research proposals and published papers.
Eventually, I enrolled as a graduate student in the Department of Cell and Molecular Biology in the fall of 2012. For the next five years, Rachel Wright was my "partner-in-crime" when it came to studying for exams, writing grant proposals, doing yoga, seeing live bands, and navigating life's hurdles. In the classroom, Rick Russel, Jeff Gross, Ruth Buskirk, and Ed Marcotte helped me develop a deep understanding of genetics, molecular biology, systems biology, and evolution that I've carried with me throughout my career. Claus Wilke never formally taught or mentored me, but his online blog and virtual books were a constant information and advice. I am grateful to Vishy Iyer, Andrea Gore, and John Mihic, Nancy Moran for their service on my qualifying examination and thesis proposal committees. The summer of my first year in grad school, Hans introduced me to a beautiful community of neuroscientists that are united by the historic "Neural Systems and Behavior Course", which takes place for eight weeks every summer at the Marine Biological Laboratory in Woods Hole Massachusetts. It was here that I developed my thesis project and gained valuable experience mentoring students. There was undeniable synergy between teaching and doing science in the highly productive Neural Systems and Behavior environment. Proximity to my collaborator was critical for interpreting experimental results while questions from students pushed me to understand my approach even better.
I want to thank the other Co-Director and my collaborator, André Fenton, for all the wisdom, creativity, and patience he brought to my thesis research projects over the years. I thank Hsin-Yi (Maddy) Kao, Ain Chung, and Juan Marcos Alarcon for their tireless dedication to these collaborative research projects we conducted during the summers of 2013-2016. I think it is incredible that we were able to walk into an empty room and build a laboratory designed specially to carry out the research described in my thesis (Appendix A1). The experiments from the first summer (Appendix B) and second summer were foundational in that they helped us identify strength and weakness of our collaboration.
As for teaching, my goal at the Neural Systems and Behavior Course was to build a new 2-week module where students could learn molecular approaches to complement behavioral and electrophysiological methods used in non-traditional species. Primarily, I taught students how to use quantitative real-time PCR and bioinformatics for RNA sequencing analysis1–3. I thank David Shultz and Eva Fischer for being a 'shining beacons of humanity' and demonstrating how to foster learning in a molecular biology teaching lab. There are too many to name individually, but I want to thank all the NS&B students, faculty, and staff who spent nearly every waking moment in the laboratory in pursuit of scientific knowledge and discovery.
The spring of my second year in graduate school, Hans hired me to be the training and outreach coordinator for the Center for Computational Biology and Bioinformatics, and it was here that I met a diverse community of scientists who use and love bioinformatics. I thank all the graduate students who volunteered their time leading the peer-led working groups where I shared our newfound knowledge and helped each other troubleshoot problems in R and Python. I thank Scott Hunicke Smith, Dhivya Arrassappan, Anna Battenhouse, Benni Goetz, and Dennis Wylie for developing the bioinformatic consulting group, which helped me build a strong foundation in data-driven discovery. I especially thank Laurie Alvarez and Nicole Elmer for orchestrating all the social events that brought us together.
I'm so grateful April Wright introduced me to the wonderful Software Carpentry and Data Carpentry Communities in the winter of 2015 at the exact moment when I needed and wanted it most. I was looking for role models who taught reproducible bioinformatics, and I hit the jackpot. I'm especially grateful to Greg Wilson and Tracy Teal who recognized my potential and opened doors that I didn't even know existed. Kate Hertweck became my constant companion for teaching, mentoring, and organizational governance (sometimes in real life but usually through virtual meetings). Christina Koch, Erin Becker, and Sue McClatchy helped me learn educational pedagogy, which allowed me to start thinking about the science of learning in the classroom and how it relates to the neuromolecular basis of learning and memory. I can't wait to see how the Carpentry communities continue to grow and spread the best-practices for research and teaching to people all around the world.
I want to close by thanking the thesis committee members and the Hofmann lab members who have guided me across the finish line. I thank Laura Colgin for the most elegant descriptions and illustrations of how the hippocampus works. I thank Boris Zemelman for keeping me up to date on cutting-edge research in molecular neuroscience. I thank Mikhail Matz always responding to my request for new functions or helping me troubleshoot errors associated with various R packages. Again, I thank André Fenton for the wisdom, creativity, patience, and dedication he brought to this research. I want to thank Rebecca Young-Brim, Tessa Solomon Lane, Mariana Rodriguez-Santos, Caitlin Friesen, Eric Brenner, and Isaac Miller-Crews for helping me craft perfect figures at our 'figure it out' meetings and for making the Hofmann lab such a friendly and productive environment.
I also feel like its worth thanking all the people I follow on Twitter. Thanks for sharing your stories and tweeting links to cool things. I feel like Twitter gives me access to a world-wide community of scientists, teachers, artists, and writers that give me advice and inspiration for my work. I feel so strongly about connecting with colleagues in geographically diverse places that I even wrote a blog post it . Finally, I want to thank my family, friends, and colleagues who attended my public thesis defense. Your support and insightful comments inspire me to continue exploring scientific unknowns and sharing my findings.