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Discovering the Scientist Within Me

CSM Lab

Published

7 years ago

on

– Stefanie Morgan –

 – Doctoral Student in Cancer Biology at Stanford University –

[dropcap]T[/dropcap]he first time I met a scientist was in college. Prior to then, science seemed just an abstract concept that was reserved for the unusually intelligent. As a student at the local community college who’d fallen through many educational cracks and lacked a real high school diploma, I didn’t consider myself particularly intelligent. Further, as the first person in my religious and strongly traditional family to attend college, my choice to pursue formal higher education of any kind – especially to take science classes – was not strongly encouraged.

Full of self-doubt and uncertainty about whether I belonged in college, I was quite anxious about the introductory Biology class. I was quite certain everyone else knew far more than I did. But the course was required so there was no choice but to do it. Within a few short weeks, I was so glad that I’d enrolled in the class, because I got to explore magical biological processes I’d never heard of before. The course unveiled new worlds of vast wonder that got me engrossed in science. When the class was over, I looked for more classes in all areas of science that I could find, exploring psychology, chemistry, anatomy, statistics, and more. I learned that it didn’t take a genius to understand and excel in these fields. One simply needed to have a genuine curiosity about life. 

Stefanie Morgan

This interest in science sparked an enthusiasm for academia broadly, and I fell in love with education. I finished community college, transferred to a small 4-year state school, and studied both psychology and biology given my fascination with figuring out the underlying workings of the brain. I discovered the writings of Dr. Oliver Sacks, and spent many late nights between the jobs that paid for my classes reading the wild tales of Dr. Sacks’ medical adventures.

Within a few months at the 4-year college, a professor asked us if we were interested in joining her research group. Having no idea what this was, I went to find out. It was a choice that would change my life. If science was fascinating, research was incredible! I could manipulate finer processes of the concepts I’d studied in textbooks, and discover new truths about the dynamic environment. I could share these findings with others at meetings and in presentations, and teach others about the amazing scientific discoveries I’d found. It was a dream!  

After graduation, it was a struggle to figure out how to stay in science and do the “right” version of what I loved. The questions plagued me constantly: Did I want to complete more schooling? Should I be a nurse, a doctor, a researcher, or something else entirely? Was I even appropriately prepared for any of these things? Without family members experienced in these matters to advise and guide the way, the beautiful freedom of academia became overwhelming. I pondered deeply as I struggled to identify the best choice, and to prove to my family that I hadn’t made a wild, foolish, and slightly expensive mistake in going to college for a degree in two science fields. I knew I did not want to wait tables and tend bar forever. I knew I liked research. Slowly, I came to recognize I really loved research, and the choice became instantly clear – I could become a researcher! It would take a bit more work, but this did not frighten me. And when I was done, I would be a scientist forever.

The only thing the stood in the way of pursuing a career as a scientist was my anxiety about failing in the process. I had surprised myself with how well I’d done in school so far, but the sneaky fear that I’d reach my intellectual limit was always lurking. Though others saw me as a bright and talented young woman, I saw myself only as a poor small-town kid without a high school diploma. “Eventually they’ll find out I’m not that smart, and they’ll realize they made a mistake in letting me in,” I’d always think. So, instead of jumping in head-first, I chose to test the waters.

Never be afraid to push your limits and explore new paths in science.  It will be an extraordinary and life changing experience that might someday lead you to also be able to say, “I am a scientist.”

I figured could be a science assistant to a more senior scientist. Why? Well, I knew that the experience would allow me to see what the life of a scientist was like, and also to determine how I would fit in with real life scientists. The experience would allow me to determine whether I could keep up with them at all. It was also a good way to get more research experience, which I would need if I was to embark upon a career in science.

This was the second life changing decision about science I made. Even as a junior scientist, I was a scientist. I got to go to the hospital and receive samples from cancer patients, bring them back to my bench and analyze them to figure out how to best treat and save the life of this living person just a few hundred feet away. It was everything I hoped and more.

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As a junior scientist, I quickly realized I wanted to be a senior scientist. This meant I needed to get a doctorate. This seemed like a huge and committed step for someone whose relatives held only high school diplomas. Again, the fear of failure reared its ugly head. What if I wasn’t qualified enough to get into a doctoral program? I was coming from a small state school. How could I ever compete with students from fancier schools who had access to more opportunities and resources? And how would I ever afford 5+ more years of school?

I expressed my fears to my research mentor. She actually laughed! She assured me that I was every bit as qualified. May be even more qualified! She also explained that doctoral programs in science were almost always free, and they in fact paid you to go. So, I applied. At her urging, I included Stanford in the list of applications. No one was more shocked than I when the acceptance letter came. Here was going to be a whole new world of anxiety, potential failure, but also an enormous opportunity. I could not only become a fully-fledged scientist, but I had an opportunity to become one of the top scientists in my field. I moved across the country with two suitcases and began my journey to becoming a scientist in earnest.

Though my time at Stanford has not always been easy, I have had opportunities beyond my wildest imagination. Fear of failing relative to my extremely well-educated peers has reared its ugly head often. For example, in my first week of classes at Stanford, I learned a few of my classmates had worked with the teams that had made extremely notable breakthroughs with CRISPR technology just a few months earlier. I hadn’t even heard of CRISPR, and was far too embarrassed to ask. Everyone else clearly knew exactly what it was. Events like this piled up quickly in my first months of graduate school. Before long, I was sure Stanford was going to realize they made a mistake in admitting me and send me back home before the first year was over. Fortunately, they didn’t, and I studied harder than ever to catch up to my classmates in-order to build my knowledge base to match theirs. I’ve taken advantage of every opportunity, and often remind myself to push through when things are not going my way, because often the greatest reward lies just on the other side of the difficulty.

Though I never received a high school diploma, in a few short months I will receive a Ph.D. from Stanford University. It is extremely exciting to be on the frontier and explore the unknown aspects of science. I am honored to be able to share my exploration with others. Without overcoming the initial fear and trying something new, I would never have gotten this opportunity. My advice? Never be afraid to push your limits and explore new paths in science.  It will be an extraordinary and life changing experience that might someday lead you to also be able to say, “I am a scientist.”

Publications from Stefanie L. Morgan 

Morgan SL, Mariano NC, Bermudez A, Arruda NL, Wu F, Luo Y, Shankar G, Jia L, Chen H, Hu J, Hoffman AR, Huang C, Pitteri SJ, Wang KC. 2017. Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping. Nat Communications, 8:15993. doi: 10.1038/ncomms15993.

Morgan SL, Seggio JA, Nascimento NF, Huh DD, Hicks JA, Sharp KA, Axelrod JD, Wang KC. 2016. The phenotypic effects of royal jelly on wild-type D. melanogaster are strain-specific. PLoS One. 11(8): e0159456. doi: 10.1371/journal.pone.0159456. PMID: 27486863

Luo Y, Morgan SL, Wang KC. 2016. PICSAR: Long non-coding RNA in cutaneous squamous cell carcinoma. J Invest Dermatol. 136(8):1541-2. doi: 10.1016/j.jid.2016.04.013. PMID: 27450499.

Morgan SL, Medina JE, Taylor MM, Dinulescu DM. 2014. Targeting platinum resistant disease in ovarian cancer. Curr Med Chem. 21(26):3009-20. PMID: 24735363

Morgan SL, Wyant GA, Dinulescu DM. 2013. “Take it up a NOTCH”: novel strategies for cancer therapy. Cell Cycle. 12(2):191-2. doi: 10.4161/cc.23375. PMID: 23287472.

McAuliffe SM*, Morgan SL* et al. 2012. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc Natl Acad Sci U S A. 109(43):E2939-48. doi: 10.1073/pnas.1206400109. PMID: 23019585.

*Authors contributed equally to this work

Highlighted articles featuring recent publication:

Nature Methods: go.nature.com/2iNJPsk

Stanford Medicine SCOPE: shar.es/1TpCv8

SBI Marketing: https://www.systembio.com/crispr-cas9-systems/cloud9-gene-expression-regulation

Cover image by Avi Chomotovski  from Pixabay | CC0 Creative Commons

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CivicSciTimes - Stories in Science

Unexpected Stories and Spindle Mistakes: Discovering that Wild-type Cells are Full of Surprises

CSM Lab

Published

3 months ago

on

July 5, 2024

By

Natalie Nannas

Natalie Nannas is an Associate Professor of Biology at Hamilton College in Clinton, NY. She teaches courses in genetics, molecular biology, and bioethics. Dr. Nannas graduated from Grinnell College with bachelor’s degrees in biological chemistry and French. She received her Master’s and PhD from Harvard University in molecular biology and genetics. Dr. Nannas conducted her postdoctoral research at the University of Georgia where she won a National Science Foundation Plant Genome Postdoctoral Fellowship. At Hamilton College, Dr. Nannas enjoys teaching and sharing her passion for microscopy with her undergraduate research students. When not glued to a microscope, she loves spending time with her husband and two daughters. The narrative below by Natalie Nannas captures the human stories behind the science from a 2022 paper titled “Frequent spindle errors require structural rearrangement to complete meiosis in Zea mays” which was published by her group in 2022 in the International Journal of Molecular Sciences.

Science never works out the way we plan. As scientists, we ask questions, hypothesize and outline our goals … then reality of science occurs. The reality of science is often full of failed controls, endless troubleshooting, and sometimes strange findings that lead us in new and unpredictable directions. Our publications give the impression that we planned these scientific journeys from the beginning and do not tell the human side of the process with all of its twists and turns, dead-ends and U-turns. I want to tell you the real story behind my first publication as a faculty member with my own lab. It did not go as planned due to the COVID-19 pandemic. My lab was shut down in the middle of our investigation, and my students and I were unable to generate new data. In the beginning, it seemed like we were stranded with only control data and no story to tell, but the time away from the lab allowed us to spend more time looking carefully at wild-type cells. What seemed like a dead-end suddenly became its own story when we found something unexpected hiding within microscopy movies. Our wild-type cells were making mistakes, attempting fixes and changing directions, just like we do as scientists.

My scientific journey began with flickering green lights and a microscope (you can read more about it here). As an undergraduate, I was mesmerized by the beauty of watching living cells shuffle fluorescently labeled proteins throughout their cytoplasm. I followed this passion for microscopy into my doctoral dissertation research at Harvard University where I investigated how yeast cells build the machinery needed to pull their chromosomes apart. This machinery is a dynamic collection of long protein tubes called microtubules and other organizing proteins that help move and shuffle microtubules. I loved watching the delicate dance of chromosomes interacting with microtubules of the spindle, and I wanted to continue studying this process in my postdoctoral studies.

During postdoctoral studies at the University of Georgia, I won a fellowship from the National Science Foundation to develop a new technique in microscopy. No one had ever watched plants building their spindles in meiosis, the specialized cell division that produces egg and sperm. Other scientists had performed beautiful microscopy studies observing how mitotic spindles function inside of plant cells, but due to the technical challenges, no one had ever observed live plant cells building spindles in meiosis. I was thrilled to take on this challenge by using version of maize that had fluorescently labeled tubulin, the protein that makes up microtubules of the spindle. With this line of maize, spindles would glow fluorescent green, allowing me to image if only I could extract the meiotic cells.

Dr. Natalie Nannas

We were so busy collecting data and prepping for our mutant studies that we never really took time to analyze the wild-type cells.

After almost a year spent dissecting maize plants, I finally managed to develop a method to isolate these tiny cells and keep them alive in a growth media long enough to image them. This new method of live imaging was going to serve as the foundation of my new lab at Hamilton College, a primarily undergraduate institution. With my students, I planned to investigate the pathways governed spindle assembly. Most animal mitotic cells have a structure called a centrosome that dictates how spindles are formed; however, female animal meiotic cells lack these structures and must use other pathways to direct spindle assembly. Plants also lack centrosomes, and I wanted to inhibit these known animal pathways in our plant live imaging system.

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As I set up my lab, my students and I collected live movies of wild-type maize cells building their spindles. I told my students and myself that these movies were not the main event, they were just the control cells so we would have a baseline comparison for our experimental conditions. We were so busy collecting data and prepping for our mutant studies that we never really took the time to analyze the wild-type cells. At the surface level, they built spindles and segregated chromosomes in a generally expected amount of time, so we focused on preparing for our upcoming experiments…. then March 2020 occurred.

The pandemic forced us to slow down and look more carefully at our wild-type data, and I am grateful for the detour.

My students headed home for spring break with a warning that there may be a delay in coming back to campus due to the spread of COVID-19. None of us were prepared for the shutdown that followed. Like many colleges and universities, our campus was closed for the remainder of the spring 2020 semester and the summer of 2020. My students and I began meeting on Zoom, trying to make a new plan for our research. The only data we had to work with were the microscopy of wild-type maize cells, so we decided to spend time digging more deeply into these movies. Originally, we had only measured the total time it took to build a spindle as it would be a baseline for comparison to our mutants. We had not looked carefully at any of the intermediate time points in the assembly process. When my students looked more closely at our movies, they discovered that wild-type cells built an incorrectly shaped spindle over 60% of the time!

We found that maize meiotic cells often built spindles with three poles instead of two, and they had to actively rearrange their spindle structure to correct this mistake. We also found that in these cells, there was a delay in meiosis as cells refused to progress until this correction had been made. This is an exciting discovery as it showed that plants are error-prone in their spindle assembly, much like human female meiotic cells. Our findings also suggested that meiotic cells were monitoring their spindle shape when determining if they should move forward in meiosis. Previous work has shown that cells monitor the attachment of chromosomes to the spindle to make this decision, but our work adds a new dimension, showing that they also monitor spindle shape. As we continued to analyze our videos, we also learned that cells corrected their spindle morphology in a predictable way. They always collapsed the two poles that were closest together, creating a single pole and resulting in a correct bipolar spindle.

The image shows the first page of the paper which can be accessed here.

My students and I had begun our scientific journey planning to breeze over wild-type cells, moving on to what we envisioned would be a more exciting story of spindle mutants. The pandemic forced us to slow down and look more carefully at our wild-type data, and I am grateful for the detour. I rediscovered my love of closely watching flickering green fluorescent lights, the dance of microtubules sliding into place or making missteps and shuffling into new arrangements. Watching life attempt a complicated process, make mistakes, and try again, is a lesson that never grows old. It reminds me that our scientific journeys are just the same, they start in one direction but are fluid and constantly changing, and hopefully, they end with a functional spindle!

Read the Published Paper

Weiss, J.D., McVey, S.L., Stinebaugh, S.E., Sullivan, C.F., Dawe, R.K., and N.J. Nannas. 2022. Frequent spindle errors require structural rearrangement to complete meiosis in Zea mays. International Journal of Molecular Sciences, 23 (8):4293–4312.

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ABOUT: Stories in Science is a special series on the Civic Science Times. The main aim is to document the first-hand accounts of the human stories behind the science being published by scientists around the world. Such stories are an important element behind the civic nature of science.

SUBMISSION: Click here to access the story guidelines and submission portal. Please note that not all stories are accepted for publication. After submission, we will let you know whether we have selected the story for the review process.

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