Nothing beats hands-on, immersive experience when you’re trying to learn something new. This is true whether you’re figuring out how to use a screwdriver, studying a new language, or learning a profession. If your aim is to become a world-class researcher in the biological sciences, Princeton’s Jodi Schottenfeld-Roames, a senior lecturer in the Department of Molecular Biology (MOL), will teach you what you need to get started by getting you involved with actual research, such as that which led to a paper published October 8, 2024 in Proceedings of the National Academy of Sciences (PNAS).

Schottenfeld-Roames is the lab director for the core laboratory course MOL 350, a class that is taken by undergraduate molecular biology majors in their junior year at Princeton. Schottenfeld-Roames subscribes to the philosophy that students pursuing a career in the biological sciences need to know much more than how to transfer around tiny amounts of liquid with a pipettor, or how to use a microscope; to do good science, students also have to know how to think like a scientist. This includes learning how to gather the background information needed to formulate a hypothesis, design experiments to test that hypothesis, and then draw conclusions from the observations made. Traditional lab classes try to do this by tasking students with replicating established research successes, but students in MOL 350 learn by conducting original research.

“A lot of the work that's in our PNAS paper came out of a desire on my part to improve the quality of datasets students collect and analyze in the course” says Schottenfeld-Roames.

The paper, which Schottenfeld-Roames coauthored with MOL faculty member Stanislav “Stas” Shvartsman, postdoctoral fellow Tatiana Gavrilchenko, and colleagues, deals with a topic of special interest to Schottenfeld-Roames. She had studied fly development as a postdoctoral fellow, investigating the genes and proteins that guide development of a special type of cell found in fly larvae, called the terminal cell. In these animals, oxygen is delivered to larval tissues by an elaborately branched airway network that expands as the larva grows. Terminal cells are found at the very end of each branch of the respiratory network, and themselves have a highly branched cell shape. 

“How does the terminal cell grow and scale within an organism that's also growing? How does it take on the beautiful branched structure that lets it perform its function? Stas and I started chatting about this system and it happened to touch on a lot of aspects of his own work so we started finding places to collaborate,” said Schottenfeld-Roames. 

“I knew that the tracheal system can be a model for some of the questions we were studying in the lab,” said Shvartsman. “I also knew that Jodi is an expert in this system and uses it in her class. Together, we put together a project that gave us several interesting research questions.”

Schottenfeld-Roames knew she wanted MOL 350 students to investigate fly genes that could potentially affect terminal cell shape, but to do this she first needed to decide what types of measurements students could take to generate useful data. Gavrilchenko, together with graduate student Lena Barrett, worked under Shvartsman’s supervision to develop a list of metrics for students to observe. Schottenfeld-Roames then designed experiments for MOL 350 students to conduct to gather data using these metrics. She also used the opportunity to collaborate with Shvartsman, applying these metrics to terminal cells during periods of larval growth. 

“My Research Specialist in the teaching labs, Tanner Simpson, did a ton of work for this paper. Tanner designed a method to immobilize larvae that permits us to do time-lapse imaging of their terminal cells” said Schottenfeld-Roames. “We are the first people to observe the branching process in these cells over the first 48 hours of larval development.”

Analysis of the imaging data allowed Gavrilchenko and Shvartsman to build a mathematical model that accurately mimics many features of terminal cell growth. 

“We learned that a relatively simple combination of stretching and branching can explain the dynamic growth pattern of terminal cells. Describing these cells in these terms helps to focus our current effort on the intracellular processes that control the elongation of existing branches and the formation of new ones,” said Shvartsman.

In light of this discovery, MOL 350 students were given independent projects to investigate how loss of particular genes affect these different aspects of terminal cell growth. Some of the data they’ve gathered will feature in a later publication, and could lead to useful insights into the growth of other branching cell types such as neurons, with implications for human health and disease.

Citation: Tatyana Gavrilchenko, Alison G. Simpkins, Tanner Simpson, Lena A. Barrett, Pauline Hansen, Stanislav Shvartsman, and Jodi Schottenfeld-Roames. The Drosophila tracheal terminal cell as a model for branching morphogenesis. 2024. PNAS. DOI: 10.1073/pnas.2404462121