Discovering Where Two Paths Cross: A Quest in Protein Functioning

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As a transfer student to Northwestern, I knew I wanted to become involved in research in some capacity. I joined a molecular biosciences lab as an undergraduate researcher during my junior year to study the structure and function of proteins. I wanted to investigate how proteins work, and particularly how the molecular structure of a protein relates to its function.

My research focused ­on a specific protein, what scientists call a protein of interest. My protein of interest was the suppressor of defective silencing 3 or Sds3 for short. Sds3 forms a long, extended helical structure, sort of like a long, loose spring. At each end of the long helix, Sds3 is attached to a large protein complex. One of Sds3’s particular functions is that it can overlap with other Sds3 molecules, bringing two of these larger complexes into close proximity to one another.

Think of two long Sds3 proteins coming together like two bike paths merging in the woods. The paths start out separately, and at one point come together. The paths travel along concurrently for some time and, after a while, they go off in their separate directions. Scientists knew that two SdS3s paths overlap somewhere along their long spirals, but we didn’t know exactly where. My job was to chart the Sds3 trail map to find this point of overlap.

Sds3 is a long, extended helix made up of smaller sub-sections called domains.  I wanted to know specifically about domain 1 and domain 2. What role do both – or either – of the domains play in the overlapping of two Sds3 proteins?

I predicted that two Sds3 proteins would overlap at domain 1 – I thought of it as my first mile-marker along the path. This hypothesis came from other research, which found a sister protein (with two similar domains) overlaps at domain 1. To test my hypothesis, I made mutations to my protein to disrupt the function of its first domain. If I was correct, the paths wouldn’t cross anymore. But disrupting domain 1 didn’t affect the overlap in my experiments. My paths still crossed despite my changes, so domain 1 could not be where the crossing occurred. Based on previous research, these results were shocking but not discouraging. I was motivated and had even more questions. What is the overlapping region of Sds3 if it’s not domain 1?

I turned my attention to domain 2. I made mutations, altering its function just like I had with domain 1, testing to see if this would affect the paths crossing. As it turns out, the results I got were pretty interesting. My experiments showed that altering domain 2 did disrupt the ability of Sds3 to overlap with itself.

It turns out that mile-marker two is where Sds3 paths cross. These results were interesting since my initial, inaccurate prediction was based on existing research. While unexpected, these surprising results were welcome. This new information is one more piece of a larger puzzle, telling us how Sds3 behaves and the role that it plays in the larger protein complex -- which, in turn, tells us about the structure and function of large multi-protein complexes and the important roles they play in gene regulation in our body.

My undergraduate research project fascinated me and I learned a lot from the experience, not only about myself as a scientist, but also about the research process in general. While I initially was under the impression that research was all about producing positive, game-changing results, now I know that is rarely how things happen. While I was in this lab, my mentor told me that 90% of research is failure – and, importantly, what you learn from that failure carries you through to the rest of your experiments. It is experiences and lessons like these during my undergraduate research career that led me to pursue a future in science. This past year, I began my graduate school journey, choosing to pursue my PhD in molecular biosciences at Northwestern, continuing to investigate new proteins and their role in the cells which make up the human body.

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