Looking back at the past ten weeks, I spent interning at Gladstone Institute for Virology Research. I am so grateful to have had this incredible opportunity and learned so much about the science world. One of my main goals, this summer, was to try to understand what it is like to be a researcher and connect with some of the Lab members, in order to learn about both the challenges and excitements of working in a lab. One of the Research assistants, who is currently applying to medical school after two years doing research, took the time to talk with my lab partner and me about his experience. As someone not so much older than me, who am relatively new to the research world, I found his comments really insightful. One thing he spoke a lot about was that while labs are often friendly places and there is collaboration to some extent within and between labs, research for the most part is a very individual field. Each researcher is exploring a very specific question that likely no one else is pursuing in the same way. Thus, the individual is likely the expert on that particular question, so if they are stuck, they can ask others for technical help or advise on new procedures. However, the ultimate decision making is left to the individual. This responsibility can be extremely empowering in that one must realize that in order for their project to succeed it is up to them as individuals to make it happen. Simultaneously, this pressure can be very overwhelming especially since breakthroughs are rare and not guaranteed. Not every experiment leads to a revolutionary discovery, and though, you may be on time; you may never discover something significant. Additionally, many important scientific discoveries occurred by accident while exploring a different question.
Paradoxically, though the research process is very individualized, the accumulation of knowledge is collective. All researchers depend on the research of others to build off and develop new questions. They are always reading journals and staying up to date with new discoveries both specifically related to their question and, more generally, in the field. As each new discovery is uncovered, it is added to the ever growing body of knowledge that constitutes our collective understanding of the world. Though, sometimes, it is hard to understand the value of a particular piece of information at a given time, the same fact may lead to an important revelation when looked at alongside a future discovery. In some ways, I view research as one of those Scratch Art projects, where you scratch a way a black paper to slowly reveal an image underneath. Slowly, slowly as we continue to research and explore the world over thousands of years, we are beginning to see a clearer picture. At the same time, research seems to me like a Jawbreaker. Every time you break through a layer you reach a new one. For every answer, we seem to discover that there are a hundred new questions. The more we learn, the more we realize we don’t know; each new discovery is just a scratch on the surface of what there is to find out.
While I have really enjoyed my time in the lab, I do not think I am going to pursue a career in research. I like the creative aspects of it; coming up with new questions, analyzing results, and thinking of new approaches but the slow nature of research and the emphasis on repetition would be challenging for me. I think that I am more suited for a career in science education. The last few weeks of the summer, I interned in the Teacher Institute at Exploratorium Museum. The Teacher Institute runs seminars for science teachers to help them develop curricula and classroom practices that promote inquiry based learning and get students excited about science. Thinking about these two experiences together makes me reflect on how information is accumulated, compiled, and transmitted. Everything we know in science has come from observation and research. Slowly, with tiny discovery after discovery, we have begun to reveal a more complete picture of the world. I was talking to my mom recently, and she said that when she took biology, even though it wasn’t that long ago, there was so much less material because the science knew so much less about how the body works and that some of the things that are considered common knowledge today had not even been discovered at the time. I have been thinking a lot about the main goals of science educations: to what extent is it about teaching content and transmitting the ever growing body of what we consider basic scientific knowledge, and to what extent is it about providing the tools for future exploration? I hope to take what I learned, this summer, and what I will hopefully learn in the coming years to pursue a career in science education, in order to provide students with the skills and information necessary to produce new ideas and discoveries.
These last few weeks in the lab have been both really exciting and challenging. After completing the first main step of the transformation, inserting a galactose sequence into the virus DNA, we began attempting the second phase. The process is very similar but has a much lower efficiency rate, so we had to be very precise in our technique. We prepared the sample and repeated the transformation procedure, this time, seeking to replace the galactose sequence with a DHFR sequence. Having already performed the procedure twice, we were a little more comfortable with the equipment; the process went a lot smoother. Unfortunately, we missed an important step in the protocol, and recovered our samples for only an hour (as we did in the first step) not for four hours as it was necessary, here. We decided to continue with the process - with the hope that even though the samples did not recover for the desired amount – maybe, we would get lucky and get a colony from transformed bacteria. However, after growing the samples on plates and sequencing the DNA, we determined that the colonies did not contain the desired sequences. A few days later, we repeated the entire procedure; this time, we had no major mistakes. Although after sequencing the DNA we discovered that not only was there no DHFR - and we noticed that the GalK had been removed by the negative selection from the plates - our viruses were back to how we started.
This was a little discouraging but our mentor ensured us that this was completely normal and that it usually takes a few tries. Thus, we began the process again. This time, we got some growth on our control plates, so we were not so optimistic. However, we continued with the DNA purification. The gel results came out very unclear, but we weren’t sure what the problem was. We tried many different things to figure out what the problem was by using different ladders, agarose percentages, and voltages. After 5 rounds on the Gel, we were able to get clear bands, and much to our surprise, they looked very promising. We sent the DNA to sequencing; they confirmed that the transformation was successful! Our mentor told us that he was very proud and that many professional researchers give up on this process because the procedure is so long. This was extremely gratifying and exciting that our work could be used in future experiments.
Another project we have been helping with is a ligation experiment to create viruses that each expresses a specific guide RNA. To do so, a bacterium is cut with restriction enzymes at specific locations, and then, ligation is done with a pool of guide RNA that, then, attach to the bacteria. This process is done many times until every represented guide RNA is incorporated into at least one bacteria colony, and then, each one is transfected into a virus. I have really enjoyed working on this experiment and hearing about its applications and guiding principles.
Additionally, over the last few weeks, I have been thinking a lot about how science is discovered, presented, and shared. Every Friday, the Gladstone institute hosts a seminar for all the summer interns in the building to discuss relevant topics in science and research. This past Friday, the chief editor of all Gladstone research publications came to talk to us about what makes good scientific writing. Reading scientific journals has always been something I have struggled with because - between the dense language and obscure jargon - I often have a difficult time just figuring out what concept or idea is being explored. During the workshop, we spent time discussing and rewriting sentences from scientific papers, in order to ensure that the text clearly presented the ideas. She emphasized that while there is often pressure to use complicated language and sentence structure in the scientific field; it is often detrimental to clearly convey the research. I found this really interesting and appreciated how her focus was on the best way to present research, so that it can be understood and built off on.
Working in the Weinberger lab, this summer, has been an incredible experience. I have not only been gaining lab skills and experience, but also, I have been introduced to the dynamics of the research world, where I have had the opportunity to meet passionate and committed scientists. My lab co-intern and I have been given an experiment to work on over the summer under the guidance of a postdoc, who has been encouraging us to attempt as much as possible our own trial and error. While this is challenging, and frustrating at times, it has been really exciting to dive right in and learn from our mistakes. When I was first introduced to the experiment that I would be working on: a DNA cloning and transformation experiment to create a new strain of virus, some of the concepts sounded familiar from Bio Lab in school. However, I couldn’t quite grasp their applications, and was not quite clear on the bigger picture of the project. Thankfully, everyone in the lab is super knowledgable and extremely helpful. They encouraged me to ask questions; each time someone explained something to me, it started to become clearer. I realized that, although I had learned some basics of virus anatomy and function in class, I did not know nearly enough to start comprehending more of the complicated procedures and experiments being conducted in the lab. So, I spent much of the first week, reading portions of a lab textbook on virology and watching lectures and procedures on youtube.
My next challenge was making sense of the protocol. My supervisor handed me a packet that was a hodgepodge of procedural steps, notes, and calculations composed by different researches over time. As a somewhat obsessively organized person, I knew that one of my main goals for the summer was to rewrite the protocol in a clear and direct way that contained all of the necessary information without any contradictions or confusing anecdotes. To tackle this problem, I began by reviewing the protocols, organizing them into steps, and highlighting any contradictory information. Additionally, after many conversations with other lab researchers, my co-intern and I created a pictorial schematic of the experiment that demonstrated the major processes. With each step of the experiment, we returned to our protocol and made changes and clarifications. The process itself has been at times extremely gratifying and, at times, extremely frustrating. The DNA is very sensitive; the efficiency of the transformation is pretty low, so we have had to make multiple attempts of almost every step. With this being said, we learned crucial things from each mistake and approached the next attempt much more prepared. It has been really exciting to see how the lab techniques I learned in school that seemed somewhat irrelevant and useless, at the time, actually have really important uses in labs.
While the hands-on lab work has been very interesting - probably the most eye-opening part of the summer - so far, it has been getting a glimpse of how the research world runs and witnessing the relentless pursuit of scientists to understand the world. I had the privilege, a few weeks ago, of sitting down with Dr. Weinberger and hearing about his vision and approach to scientific research. His lab is really exciting in which he has many dedicated researchers all exploring very different questions; questions that are all related by a common thread and shed light on fate decisions in viruses. Additionally, over the last few weeks, I have been able to sit down with some of the members of the lab and hear about their projects. It has been really fascinating to learn about some of the really exciting questions being explored, and the potential applications of their findings. Every Wednesday, the whole lab meets and two lab members present their research and data. Then, everyone in the lab has the opportunity to provide constructive criticism, new ideas, and discussions on future steps. Until now, I never really thought about how scientific journal articles were composed and the thought that goes into every figure, heading, and format. It has been really cool to witness how questions goes to an experiment which results in data that is then analyzed and formatted and published. There is so much thought put into every single step including presenting the data in a way that really provides the reader with an understanding of the findings. Additionally, the Gladstone institute has seminars and lectures with researchers from all over the country. It has been really interesting to see how thousands of different researches, each exploring very specific question, come together and build off each other to come to a clearer picture of how the world works. With each new finding, new questions emerge that can then be pursued. To me, it seems that successful research works almost paradoxically. You have to, at once, be extremely creative, think of new questions, new approaches, new applications that have never been considered or explored, while conducting credible experiments and reliable data in which you need to have an extremely disciplined routine and very repetitive procedure. It is often very exciting conceptually but can be very monotonous in terms of actual procedure.
Over the next few weeks, I hope to continue to meet with other members of the lab and hear about their research and their ideas. I also would like to continue in taking advantage of all the amazing resources that the Gladstone Institute offers and, successfully, complete my transformation experiment.