June 2021: In Focus

An Eye to the Future: Research on Fly Eyes Helped Prepare Undergrad for Medical School

John Majewski'sJohn Majewski’s engagement in biology research added valuable experience to his undergraduate education at the Dietrich School.

“I remember visiting Pitt; it was just really beautiful. It was a nice, bright, sunny day, and I was amazed by the Cathedral of Learning,” remembered Majewski, who graduated from the Dietrich School in May with a major in biological sciences and a minor in chemistry. “And I really liked Pitt’s high research potential. I knew going in that I really wanted to do something related to research in the sciences. And I knew Pitt was one of the top places for research in the health sciences.”

“I’m very interested in biology and chemistry,” said Majewski. “The idea that chemistry informs biology—chemistry explains it in a way. A lot of things we do in biology explain the ‘what’, but chemistry gives us that ‘why’ behind biology.”

Early in his Pitt career, Majewski enrolled in a research lab course that focused on neural tube defects. The course, taught by Associate Professor Jeffrey Hildebrand, provided hands-on laboratory experience to undergraduate students as they investigated the processes that lead to the development of the brain and spinal cord. Students dissected and performed experiments using Drosophila melanogaster—the fruit fly.

“I was working with the fruit flies there and learned all of these different techniques that Dr. Hildebrand would use for his actual, real research. And I found it quite interesting,” Majewski said. “I thought the confocal [microscope] was so interesting. We did immunofluorescence and dissecting, and then I applied for a summer fellowship at Pitt, the Mentor and Mentee Summer Fellowship Program.”

Through this fellowship, Majewski spent a summer working on a research project in Hildebrand’s lab, which evolved into a more long-term role and eventually led to his authorship on a research manuscript that was published in the journal Biology Open this year.

Majewski’s research was centered on a protein called Shroom, which is important for signaling changes in cell shape that are required to form the neural tube, the precursor that develops into the brain and spinal cord. In fruit flies, Shroom is also important for the formation of the eyes and wings. Majewski took advantage of a genetic screen developed in the Hildebrand lab that could be used to identify proteins that interact with Shroom and affect its function.

Specifically, Majewski’s project asked questions about the interaction between Shroom and another protein called Shortstop to try to understand how they worked together to change the shape of a cell.

“I examined fly eyes and wings, because we know based on previous research that Shroom is used in the fly eyes and wings, and when overexpressed, it will cause the wings to constrict apically, and they'll look more constricted. And we know in the eyes, the little ommatidia facets will be more disorganized if you overexpress Shroom,” said Majewski. “My goal was to look at Shortstop and these fly eyes and wings, and mutate it to see if it either causes greater disorganization of the eyes or increased crinkliness of the wings, or if it will cause the wings to be less constricted or the eyes to be more organized.”

Majewski honed skills in genetic crosses, fly dissection, and imaging software to understand how these proteins interacted with each other. In addition, Majewski used confocal microscopy to determine where the proteins were going within the cell.

“We saw where Shortstop was localized relative to Shroom,” Majewski said of the team’s cellular-level findings. “We found out that they are complementary to each other. Shortstop is located in this medial apical area, and Shroom is located in the peripheral apical area, which means that they probably coordinate in some way.”

Ultimately, data collected by Majewski and other students from the Neural Tube Defects course and researchers in Professor Hildebrand’s lab furthered our understanding of how Shroom contributes to cell shape changes during brain and spinal cord development.

“The biggest thing we found out is that we are able to use this screening technique in fruit flies to check out what potential regulators there are in the Shroom-dependent pathway for apical constriction,” explained Majewski. “In particular, we found out that Shortstop is required for Shroom-induced changes in tissue morphology.”

Now Majewski is headed to medical school, and he'll take with him the lessons he learned through his Dietrich School research experience. He noted how valuable it is for students to have the opportunity to perform research as part of their undergraduate experience.

“I think the importance of research as an undergraduate is whenever you read all these different textbooks and papers and biology, it's hard to really understand how they came about all these things,” Majewski said. “But when you do research, you can appreciate it at a greater level than before. For example, this whole Shroom project is very complex, but eventually this will just be uncovered as a pathway in a textbook that’ll be easy to read. You don't realize it takes years and years of research to even get to that level. Also, it's very common to fail. I've learned that you don't really appreciate how often they fail. And that's part of science too. It’s almost bad if you're succeeding 100% of the time.”

Majewski is grateful for his experience with undergraduate research and said that it had a positive impact on his career goals.

“I did learn a lot from this lab, more than I could have imagined,” said Majewski. “My experience in Dr. Hildebrand’s lab has definitely made me want to continue pursuing research in some capacity, through medical school and, potentially, the rest of my life. I really do just like seeing the ‘why’ of things, and it's cool to find out something that no one else knows in the world first. That's what I think is so interesting about research.”

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