How to Design Your Research Question

By: Matthew Lin, OUR Peer Research Ambassador

For centuries, man has attempted to find immortality to no avail. Juan Ponce de Leon couldn’t find its Fountain; alchemists threw together chemicals to manufacture an elixir of life. Yet, in the rocky depths of the ocean there exists a creature that seems to have found the secret to endless life.

No, it’s not an ancient dinosaur nor a mutant monster. Nor is it a small microscopic organism. In fact, it’s the humble lobster.

Lobsters have been known to be what’s called “biologically immortal.” Their rate of mortality and cellular aging appears to be decreased or even stable when compared to its chronological age. Reports have said that older lobsters are even more fertile than younger ones. The oldest reported lobster was 140-years-old.

What’s their secret?

In this week’s blog, I want to talk about how you can construct your own research questions and even, perhaps, your own research project. I think the recipe for an effective research question consists of four important ingredients:

  1. A good question starts with bad questions
  2. It tells a story
  3. It should make sense
  4. It should be ambitious but attainable

 A good question starts with bad questions.

 Lobsters are wonky creatures. Have you ever looked at a lobster? I mean, really looked at one? Their legs are bunched up underneath an abdomen that is plated, they have a tail that seems to serve little purpose, their claws are monstrosities that don’t even act to catch prey – and they have beady little eyes that sit atop stalks.

How were these traits evolutionarily advantageous? What causes a brown and blue lobster turn red when cooked? How does the process of molting even occur? Are lobsters friends with other lobsters? Seriously though, what’s up with the eyes?

In all seriousness, the process of coming up with a good question is much like learning how to blow your first bubblegum bubble. You’re going to look and sound weird at the beginning, but eventually you’ll figure out what works and what doesn’t. Don’t be afraid to think outside the box or really question the fundamental basis of how, what, or why something is the way it is. Your question – however stupid you might think it is – is still a question. Once you arrive at one that’s worth answering, you might be surprised at your journey to that question, and then you can begin to think about the next steps in honing your research question.

Question: How are lobsters immortal?

A research question tells a story.

 In order to study immortality, we must define what it is not. Thankfully, mortality has been studied extensively. Cells are limited by what is called the Hayflick limit. This limit states that a cell has a certain number of divisions it can go through before it can no longer replicate itself faithfully. Hayflick researched this limitation and discovered that it was around 40 to 60 generations.

In addition, a protein within cells known as telomerase acts to extend the ends of chromosomes (kind of like the aglets of a shoelace), so that when they are copied, the full DNA sequence is preserved. Aging and cancer are pathological states of cells wherein the telomerase functions aberrantly or to a lesser degree than other healthy cells.

Once you’ve landed more concretely on a research inquiry, do some background digging to find out the context in which you might be able to frame your question. Give body and a skeleton to the intriguing thing that’s captured your attention – can it be expanded out to effect a broader population, or can you narrow the focus even more to study it in a more in-depth way? Furthermore, what has the scientific community already discovered about the topic?

So, back to our lobster scenario. Perhaps our shelled friends are using telomerase to their advantage and avoid the obstacle of cells that otherwise lose telomerase function? Is it the case that all lobsters have somehow turned on this protein more than other animals?

Question: Is lobster immortality related to its ability to surpass the Hayflick limit, and if so, is it due to high telomerase activity and efficiency?

It should be testable and verifiable.

Just as you learned in fourth grade, the scientific method requires a hypothesis that can be tested through experimentation that will produce data to support or reject your claim.

Let’s expand on our question from the previous step a little bit more. Can we think of any ways to observe and perhaps even manipulate the function of telomerase within a lobster? From a genetic and molecular biology perspective, yes. By isolating cells from a lobster and growing them in petri dishes (what we call in vitro), we are able to change different parameters of the cells. Using a certain type of experiment (in the scientific world this is often called an “assay”), we can in fact cause the telomerase protein to increase in activity, decrease in activity, cease activity, and measure the activity using fluorescence. In addition, if we can monitor the number of times a cell divides as a result of increasing or decreasing telomerase activity, then we can answer the first part of our question.

This is probably the most daunting step that you will face in the design of a good research question, and as a young scientist you might feel unqualified and unequipped to begin thinking of answers to these issues. Don’t fear! Ask for some guidance and consult the internet. Read papers related to your topic, talk with professors doing similar work, ask upperclassmen what they think. You might strike up a nice conversation with a potential mentor that you can follow up with later on (See how to here!)

Question: Will changing the activity of telomerase in lobster cells affect their ability to divide indefinitely? More specifically, is lobster cell generation numbers are directly proportional to telomerase activity?

Hypothesis: By decreasing telomerase activity (through knockdown methods known as miRNA/siRNA/shRNA), a significant decrease in cell generation turnover will be observed.

It should be ambitious but attainable.

Lastly, your project should at this point be infinitely interesting to you. You’ve thought about several avenues of exploration that are not being done currently, you’ve done the background work in providing the context to the topic at hand, and you’ve looked into how to make it quantifiable and measurable.

If you haven’t reached out to a faculty member to maybe complete your well-thought-out project, this is a good point to identify those mentors. Conversely, you could start by reaching out to faculty and then designing a research question that fits their research work and lab (if you’re following our advice on how to secure positions within labs, this process should make sense).

The important thing to remember is that time is valuable and you must be aware of the limitations. You may not have all the time in the world to conduct research full time; your group may not have all the expertise or equipment to run the assays that you would like to complete. That’s fine! Work with your lab professor or your graduate students to make your goals manageable and achievable. The last thing you want is to design an awesome project that no one in a million years can compete.

Final Thoughts.

Ok. Now that you’ve seen my process of figuring out a good research question about lobsters, I hate to break it to you but lobsters are in fact not immortal. Older lobsters are typically prone to death from slower molting, slowing body functions, and the increased chance of being caught and eaten by us. So, if you thought my research project was one that you also found interesting – I hate to break it to you. If you do happen to find the key to immortality or the serum that will stop aging, let me know.

Have fun, think big.

Matthew Lin is a senior completing a major in Biological Sciences and minor in Chemistry. Click here to learn more about Matthew.