“Why do you want to get involved in research so early? Can’t you at least wait for a few months to get adjusted to classes?” my dad asked while taking exit 37B into Ann Arbor. We had debated it for a while on the ride from our house to my new dorm room, but I was eager to experience biology in a way very different from high school lectures. Since the first week of college, conducting experiments at the lab bench and learning more about the questions and methods in the literature have been fixtures of my schedule.
Glancing over the sequence on SnapGene, I nearly missed it. Within the middle of hundreds of nucleotides was a six base pair deletion that led to a premature stop codon. It seemed like a minute change, but zebrafish larvae with that gene mutation differed in their response to certain stimuli. As a freshman in a lab in the MCDB department, I was excited by how lectures on DNA and the genetic code were directly applicable to the creation of gene knockouts.
One of the most interesting parts of research is learning how scientists creatively use theories and concepts to develop methods for investigating various questions. Scientific questions can be big, small, commercially relevant, or extremely abstract. But all are questions that have not yet been well answered.
“Scientific questions can be big, small, commercially relevant, or extremely abstract. But all are questions that have not yet been well answered. “
Over the past summer, I spent nearly two weeks thinking about doing intron removal assays and discussing various methods and what information they could yield with a postdoc in the lab. I sketched possible experiments during lunch and thought about various controls while at home talking with my roommate. Ultimately, the postdoc and I decided that the approach wouldn’t yield much information on what we were studying; I had nothing to show for a little over 80 hours of work. Unlike in a class or lab-based course, you or the mentors who you work with are deciding which questions to address. That leads to some of the most difficult and enjoyable aspects of doing research. It is difficult to know which questions are worth asking or how to answer them. So why do research?
I remember standing at the lab bench with a graduate student, puzzling over a surprising result to an assay. My brain awash with facts about the mechanisms underlying the experiment, I struggled to come up with a clear hypothesis. The controls looked good and the result was clear, but no one had predicted it. Well maybe, uh… hmmm. Huh. I had no luck with cogent thoughts, but was intrigued by the data. In trying to investigate the question, you try to design approaches to yield new insight, often conducting experiments no one has done before. How was I going to move ahead from this experiment? I am still trying to answer that. Determining which questions to ask and subsequently designing these experiments requires learning a great deal about what has previously been done.
And that requires reading. Scrolling through a list of references on retrotransposition during my first week in a new lab, I felt overwhelmed by the sheer number of journal articles. Ever ready to procrastinate, I organized them by sub-topic and called it a day. Over the next few weeks, I thought that I was beginning to understand which aspects of retrotransposons were characterized and how scientists had studied them. Taking notes on frequency of retrotransposition in mammals, I hesitated and opened a previous article. The two frequencies were different and had been used to argue for distinct conclusions. Which should I trust? Talking with graduate students, postdocs, and the professor in the lab helped me work towards critically examining an article, reviewing the data, methods, and interpretations in addition to noting the author’s arguments. It’s a work in progress, but academic papers engage me more than textbooks, and I appreciate the guidance of more senior scientists.
The questions others in the field have asked and the pieces of information that remain unknown shape what I examine. Trying to develop experiments for these investigations is difficult. I often propose a “simple” method, only to realize its shortcomings or complications in interpreting the results of such an experiment. However, the methods others have employed spur me to try various approaches to a question. Once I decide on a question and the experiments I would like to try, the only thing left to do is carry them out and analyze the data. Right? At least in theory. But as I am often reminded when I draw up plans for a new experiment, theory does not always translate into practice.
Evidently the third try is not always the charm. It was around my 60th attempt before I finally managed to dissect out an intact larval fly brain. A few weeks later, it was clear that a certain genetic cross of fruit flies was not working, and that different experiments would have to be conducted to confirm the nature of a gene mutation. I frequently tell myself to persevere or modify my approach to a question. I remind myself that easy and relevant experiments rarely present themselves.
“Evidently the third try is not always the charm. It was around my 60th attempt before I finally managed to dissect out an intact larval fly brain.”
However, not all issues can be identified or answered with current knowledge and techniques. When I started asking other members of the lab about how an RNA of interest was transported back into the nucleus, they explained to me why the question was good but extremely difficult to address. No clear template exists for inquiry into detailed mechanisms or factors that play a role in a cellular phenomenon. I still struggle with accepting the everyday failures during experiments and the questions that must be shelved for a date to be determined, but they are necessary parts of working on unknown aspects of a scientific field.
So is it worth going to lab between classes or reading a paper during the last good weather days of fall while your friends play frisbee outside? Depends on your interests. While I am far from being able to design experiments well, I enjoy trying to creatively design an approach to answer a specific question. Unexpected results can be due to technical errors or unexplained phenomenon, and trying to determine which one forces me to consult mentors within the lab and published papers. My favorite part is trying to determine which of the possible explanations for the data is the most likely mechanism. I am occasionally frustrated by a lack of progress in my experiments. Ok, perhaps more than occasionally. But the process of research is challenging and engaging in a way unlike any of my classes.