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The Journey Continues: Finding My Questions in Science

If it had not been for my friends and the little voice inside telling me to focus on why I had started research in the first place and to keep going, I would have almost certainly given up. – Yasmine Raya Ayman

CSM Lab

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Yasmine Raya Ayman

[su_boxbox title=”About”]Yasmine Ayman is a rising junior at Columbia College double majoring in neuroscience and philosophy. She was raised in a multicultural household in Luxembourg that makes her especially fascinated by how borderless and global science is. She wishes to continue her journey in science through pursuing academic research and science advocacy in order to effect change in society on an individual and collective level. She is currently conducting research as an Amgen Scholar in the Axel Lab. The story below was edited by Fanuel Muindi. [/su_boxbox]

[su_boxnote note_color=”#d9d8d6″]Story Key Ideas

  • Dedicate your life to something far greater than yourself
  • Search for questions that compel you to keep going
  • Science is one tool for social empowerment [/su_boxnote]

[dropcap]C[/dropcap]ognitive Scientist Daniel Dennett once said that โ€œThe secret of happiness is: Find something more important than you are and dedicate your life to it.โ€ I would say that ever since I embarked on what is slowly unfolding as my story in science, I have hearkened back to that maxim, albeit with a minor edit. That โ€œsomethingโ€ I am searching must be a question I feel especially equipped and suited to answer, since there is a plethora of important causes deserving of our time and energy. It appears to me that one of lifeโ€™s struggles is learning to focus on your own path, while having faith that others will tackle the rest. As a matter of fact, that faith and collaboration is essential in practical science as well given the many mysteries in nature that still require us to unravel together.

Yasmine Raya Ayman

I would say there are three main episodes that come to mind when I think of what distinct stages have led me to my present state. The first episode took place all the way in Japan, where I was spending my 10th grade spring break with my family. One night at dinner, our family friend who lives in Kyoto was telling us stories about his work as lead molecular geneticist at Kyoto University. He was describing one type of cells called the Induced Pluripotent Stem cells which were the next big thing at the time. He was sharing his excitement at conducting research in the field as well as the tangible impact it would have on society. It is crazy to think that this was the first time I consciously registered that being a scientist was an actual profession I could pursue. I remember being so awestruck by this possibility that I remained glued to his stories for the rest of the evening.

Of course, I quickly pledged myself to becoming a future molecular geneticist. I started reading more about the field and stumbled onto Nessa Careyโ€™s book โ€“ The Epigenetics Revolution โ€“ which served as my first science book (little did I know 5 years later I would be working on a project centered on epigenetics). I remember being very fascinated by the human studies that were tracing various metabolic or neurological abnormalities to environmental factors. I thought to myself, what better way to delve into the perplexing, yet captivating โ€œNature vs Nurtureโ€ debate than to study epigenetics. I was unconvinced by statements such as โ€œWe are our brainsโ€, because just intuitively speaking, I felt like we were so much more.

Another portal to understandingย who we areย is Alzheimerโ€™s disease. ย This is paradoxical, since Alzheimerโ€™s erodes our sense of self by graduallyย stripping away our memory until we can no longer remember the most basic facts about our lives. I came to this realization the summer following my familyโ€™s trip to Japan when I did research in the Cognitive Neurology and Alzheimerโ€™s Disease Centre (CNADC) at Northwestern University. I worked on a project investigating the molecular hallmarks of Alzheimerโ€™s pathology in human brains. This experience marked the second episode that has led me to my present state: I was formally introduced to the field of neuroscience. During my time at the CNADC, I saw my first human brain and witnessed all the steps involved in preserving it โ€” from autopsies to tissue mounting.

Concurrently, a close family friend had just been diagnosed with Alzheimerโ€™s disease and I witnessed first-hand the overt behavioral changes arising from alterations in the brainโ€™s organic matter. This experience accentuated the mysterious divide between morphology and behavior, as well as the more uneasy disconnect between the emotional labor involved in witnessing Alzheimerโ€™s pathology, and the removed academic setting in which it is carefully studied. In an attempt to reconcile these opposing sides in my academic trajectory, I planned to double major in both philosophy and neuroscience in college. I believed that one needs both the introspective and objective measures to truly understand the human mind, and hence, the elusive self.

The questions we have that so deeply compel us to keep going only help us get back up after it feels like the whole world wants us to give up.

Throughout my studies, I was often told that neuroscience has two main mandates: studying nature and understanding disease. Upon first entering college, I was much more fascinated by the latter. Prominent scientists I had met and spoken to prompted me to start searching for my โ€œquestionโ€ i.e that โ€œsomethingโ€ I would dedicate my life to. Convinced my questions would be found in pursuit of understanding memory formation and Alzheimerโ€™s disease, I started working in a cutting edge Alzheimerโ€™s and Depression research lab. The lab used novel techniques such as optogenetics to stimulate the Dentate Gyrus (DG) of the Hippocampus, a region of the brain implicated in the formation of new memories. A paper published shortly before I joined the lab had shown that stimulating the DG caused the retrieval of previously found to be lost memories in Alzheimerโ€™s diseased mice โ€” a discovery that dawned many exciting new interpretations of the disease pathology.ย 

The findings were riveting, and I gained first hand exposure to research in a field I felt viscerally moved by. I learned a lot from this lab; not only in the realm of key techniques used in neuroscience research such as immunohistochemistry, brain sectioning and genotyping, but also in the realm of instrumental soft skills required in conducting scientific research effectively. I experienced my โ€œfirstsโ€ with pipettes, microscopes and mouse surgeries, and was more confused than ever before. I began to formulate my own questions with increasing sophistication, and learned how to approach forging a path to answering them.

The research path I was carving for myself was, however, tumultuous. Amid constant failure, I found myself foolishly comparing myself to those with far more experience than myself, and returned home many nights feeling defeated. Over the summer, where I worked full time in the lab for around two months, I came face to face with my deepest flaws. I questioned myself every day, wondering whether or not I was truly cut out for academic research in neuroscience. When everything else in the lab seemed to be running so smoothly, things werenโ€™t working out as such in my hands. I faced a multitude of new obstacles that took me weeks to surmount. If it had not been for my friends and the little voice inside telling me to focus on why I had started research in the first place and to keep going, I would have almost certainly given up.

Explore Next:  A Science Outreach Story

At the end of the summer, I felt grateful for the significant learning and growing I had done that had shaped my identity as a scientist. But ultimately, I wanted to keep exploring new research avenues and exposing myself to different lab environments. Instead of moving to another Alzheimerโ€™s or cognitive neuroscience lab, I chose to dig deeper in an effort to unearth the more molecular mechanisms underlying human nature and evolution. I felt that delving into a completely new realm of research would only complement my future inquiry into disease.

I switched to a new lab and started working on a project studying Transgenerational Epigenetic Inheritance (TEI). Epigenetics literally means โ€œabove genesโ€ and it describes how the environment impacts gene expression through so-called epigenetic markers. TEI refers to the transmission of these epigenetic markers from one generation to the next, so that the descendants of the individual who was initially exposed to that environment bear the scars of their ancestors. This hits home as my father was a refugee from Iran during the Revolution where he fled from the persecution of Bahรกโ€™รญs. Stories such as these harbor sadness and trauma that could lead to cultural, but perhaps also physiological, imprints on future generations.

Serendipity reunited me with the question I was initially interested in: what makes us who we are? Eager to understand trends in historically oppressed communities and frustrated by the impasse I was feeling with how we were tackling the mental health epidemics, I was determined to understand how these susceptibilities arose. In doing so, I hope to work towards cultivating strength and resilience in individuals in an effort to help them escape the specters of crime and poverty. Pivoting from understanding disease to studying nature marks the third, and present day, episode of my story.

Bringing clarity to the complex phenomenon of TEI seems to preside in the distant future, as there is much to be unearthed when it comes to human development. However, the general principle that there are aspects of ourselves that lie out of our reach because of the unfortunate circumstances we or our ancestors have been exposed rings true. Heightening our consciousness thereof can only alleviate the burden many members of society, such as veterans or refugees, face. Further, these insights can shed light into how we can best navigate criminal justice proceedings or (re)integration into society. To me, the very real impact this research can have on people around the world illuminates both the power of basic science research and the merit of interdisciplinary approaches to real world problems. From a philosophical standpoint, this research weds our internal states with the external world, reconstructing the notion of the self as a fluid, unbounded entity โ€” one with the world around it. As such, the most recent chapter of my story in science ended up feeling the most human.

Over the past year and into this upcoming summer, I will continue to hone my skills as an undergraduate researcher and absorb as much as I can about the academic research around me. I am seizing every opportunity that comes my way. I believe in the power of science to discover physical reality and gain insights into human conduct and the life of society. And I also trust in its faith to embolden individuals like myself to investigate the world around them fearlessly. Nothing about my journey so far has been smooth, nor providential. Rather, it has been characterized by hard work and personal faith. I am lucky to have supportive mentors today; however, there were far more voices telling me I was not qualified for large parts of my story. I therefore feel compelled to help others empower themselves through science and actualize their potential. In that regard, I find science is yet another tool for social empowerment, albeit one that should mainly come from within.

Today, whether through the UN IVY STEM Connect program, a project under the Girls Education Initiative, where I host weekly science workshops with young girls in Tanzania and Rwanda via Skype, or on campus through organizing panels and conferences, I strive to advocate for science in many forms. The main message I try to communicate hearkens back to advice Bianca, my postdoc mentor, gave me to me earlier this semester when I was doubting myself: you should never base your self-worth on science as it is a mystery for us to unfold and it does not care about you. This self-worth and confidence in your abilities must come from oneโ€™s own faculties, and the onus is therefore on each individual to reflect on what environment best conduces to strengthening those inner faculties. For me this meant switching labs, but that was an example of one decision out of the many I will still have to make to buttress my own journey. ย ย ย ย ย ย 

The bottom line is that before we can dedicate our lives to that โ€œsomething” far greater than ourselves, we have to have faith in our own abilities to contribute to scientific advancements. The questions we have that so deeply compel us to keep going only help us get back up after it feels like the whole world wants us to give up.

Cover image by PIRO4D from Pixabay | Pixabay License

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CivicSciTimes - Stories in Science

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

CSM Lab

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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 Masterโ€™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 โ€œFrequent spindle errors require structural rearrangement to complete meiosis in Zea maysโ€ 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 โ€ฆ 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.

Explore Next:  Growing Up in Science: Gyorgy Buzsaki

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 experimentsโ€ฆ. 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 maysInternational Journal of Molecular Sciences, 23 (8):4293โ€“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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