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My Kaleidoscopic Journey in Science

If you observe carefully, you’ll find a similar pattern in science and life. Both teach you the same lessons. The lessons that you learn from science help you solve problems in life as well.

CSM Lab

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 – Aswathi Ashok, M.Tech – 

[su_boxbox title=”About” box_color=”#262733″]Aswathi completed her master’s degree in Biotechnology in 2016 from Vellore Institute of Technology, in Vellore, India. She aspires to become a future researcher and academician. She is also a trained and passionate Bharatanatyam dancer and Karnatic singer. She enjoys blogging during her free time. You can check out her blog on travel, food and musings on life. You can reach her via LinkedIn or email. [/su_boxbox]

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Key Points 

  • Sometimes, the things that you think you really want might not always be what you actually need.
  • Everything happens in life for a reason.
  • Trust that someday, everything will make perfect sense. Patience is one good characteristic to cultivate in science.
  • Science teaches you how to face challenges in life.[/su_boxnote]

Where it all began.

[dropcap]F[/dropcap]rom an early age, I have always been an avid reader. When I was in the fifth grade, I vividly recall hurrying to the library to get a new sequel of Nancy Drew’s books during one recess period. While browsing through the bookshelves, I stumbled on this huge book of science, which was misplaced and was instead kept in the fiction section. I am actually thankful that the book was misplaced. Why? Well, it was while browsing through the book that I first came across the word ‘camouflage’ in the context of how marine animals camouflage to catch their prey or defend themselves. I was so curious to know the meaning of the word that I took the book and ran to ask our school librarian, who explained the meaning of the word. I was thrilled to know such a behaviour/property existed. My inquisitiveness grew after this experience and I continually found myself running to the library when time permitted. I can honestly say that my passion in science began in that library all those years ago.

Everything happens in life for a reason. Trust that someday, everything will make perfect sense.

I grew up liking science and biology turned out to be my favourite. I had always dreamed of being a medical doctor because of my love for biology. I had a strong ambition to pursue medicine right from the seventh grade and passionately pursued this goal with everything that I did. 

My first major setback was when I couldn’t get into a medical college in India, despite my persistent efforts. I couldn’t understand what or where I went wrong. I did manage to get on the ranked list but my ranking wasn’t high enough to secure a seat for the incoming class. Well, it so happened that I ended up choosing to pursue a bachelor’s degree in biotechnology and biochemical engineering instead. I was heartbroken seeing the syllabus since it covered more of biochemical and engineering subjects instead of pure biology. 

Every time I looked at the syllabus, I regretted not getting a better rank for entry into medical school. I could see people around me happily enjoying their engineering studies, but despite my desperate efforts to try and blend in, I couldn’t.

Then I remembered what mom always said: “everything happens in life for a reason and that someday everything will make perfect sense.” That’s when I realised that making the most of what you are given is one of the keys to happiness. I wasn’t happy because I was failing to take advantage of all the other wonderful things that were happening around me. If I really loved the biological sciences, medicine was not the only path.

Slowly, I started to notice that there was beauty in every subject. All I needed to do was to be open to learning new things. I finally entered my third semester and from then on, it has become a beautiful journey. I then went on to pursue my master’s degree in Biotechnology, which was a real eye-opener for me. It was what I needed.

If you observe carefully, you’ll find a similar pattern in science and life. Both teach you the same lessons. The lessons that you learn from science can help you solve problems in life as well.

Over the course of my study, I realised I had this genuine curiosity and passion for research in molecular biology. I was intrigued by the term ‘molecular cloning’. It was in my masters program that I first got the chance to actually work on a molecular cloning project. This was like a dream come true. I cherished every moment spent in the lab working on the project where I conducted a functional analysis of the aspartyl protease gene. Long story short, it was a molecular cloning project done on E. coli DH5 and E. coli BL 21 bacterial strains.  I absolutely enjoyed every aspect of the project.

The main objective of the project was to study the protein expression of aspartyl protease gene after it was introduced into the prokaryotic system, E. coli and analysing their role in Oryza sative against biotic and abiotic stresses. I had finally found my true passion in life, which was in molecular biology research. I understood that, for me, true happiness was in learning through research.

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Patience is one good characteristic to cultivate in science.

Fortunately, I got an opportunity to do my final year masters dissertation for 10 months at CSIR-National Institute of Oceanography, Goa, India, where I was involved in molecular work on microalgae. The project was titled “Molecular identification of biofuel potential microalgae and PCR detection of their triacylglycerols.”

Molecular work is quite interesting, but I never said it was easy. There were times when the experiments didn’t give me the expected results. Sometimes, days – even months – would pass with no progress on my project and it always seemed to have hit rock bottom. Unlike bacteria, working with microalgae was tough. Most protocols for microalgae had not been optimised yet. Consequently, I had to repeatedly try different trial and error methods to optimize the 16S and 18S rDNA extractions and PCR amplification protocols for my samples.

There were numerous limitations throughout the process.

  • Firstly, unlike bacteria that divide rapidly, microalgae cells take about a month to grow and become visible to our naked eyes.
  • Secondly, for any molecular work, the culture must be a pure culture. Symbiotic association of microalgae with bacteria made it almost impossible for me to prepare axenic (pure) culture.

I was in a dilemma. There were days I felt my project was on a stand still mode without any progress. However, after working diligently for months to tackle the problems, I finally successfully completed my master’s thesis.

I owe it to my guide, Dr. N. Ramaiah, Chief Scientist at CSIR NIO, for his consistent support throughout my dissertation period. Something he said struck me: “if one approach doesn’t work, try solving the problem from a different perspective and that every result counts when it comes to research, be it positive or negative.” Sometimes, it so happens that – notwithstanding your meticulous efforts – you might still end up with negative results. This is still useful data.

For me, molecular biology is like oxygen. I thrive on it. I moved to Singapore in 2016 after I got married. I took the GRE exam and applied to universities in Singapore for PhD graduate programs. Additionally, I applied for jobs in the biotech sector.

After several rigorous efforts in sending applications, both for jobs and PhD studies, I finally started getting responses from the institutes I applied to. Unfortunately, I received no invitations for interviews. It was rejection after rejection.

A year later, I was overjoyed to get an interview letter from the Mechanobiology Institute, NUS for admission into the graduate program for August of 2018. The interview date was a week later. I was really hopeful that I’d get accepted since my interview went quite well. Sadly, a few days later, I received a letter informing me that my application was rejected. I felt like my world came crashing down all of a sudden. It was my dream to do a PhD in Stem Cell/Molecular Biology. This was a dream that almost came true for me and now it was gone. Tears rolled down my eyes. It really hurt.

Being an optimist, I have always tried to find something positive in everything that happens around me. As we all know, ‘no one is perfect.’ There have been times when I have felt completely devastated and have struggled to find a spark of hope in life. I knew this was another such phase. My husband, who is also my best friend in life, reminded me that things will work out at the right time and asked me to never quit trying.

So, that’s where I am right now.  I know the undying commitment and passion I have in me for molecular biology will definitely ensure that I’ll keep trying and patiently wait for things to work out. In the interim, I am also focussing on my favourite hobbies like blogging, dancing, singing, swimming, and reading, which has definitely been a great stress buster.

My message to people struggling through their tough times in life is to never resort to self-pity over your situation in life. Ups and downs are an inevitable pattern of life. Remember that if you are going through a rough patch, things will definitely get better soon. Work hard and hope for the best. Hope is the key to getting through the days of uncertainty in life.

Cover Image by Gerd Altmann from Pixabay

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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 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 maysInternational Journal of Molecular Sciences, 23 (8):4293–4312.

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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