A journey based on curiosity
By Kimberly Eaton
Catherine Scull has always believed the best research comes from scientists who are curious and unbiased.
“Some of the most amazing discoveries in history came from someone who saw an interesting system and went after it, and now it’s become revolutionary to the field,” said the 28-year-old Florence native who, in March 2020, received her doctorate in biochemistry and molecular genetics.
It was this thought process that led Scull to her graduate research area – studying a system that could be used for cancer therapy.
“My goal was to study something I think is really cool, but also has positive benefits for human health,” she said. “I didn’t get into this area of research because I’m super passionate about curing all cancer, but I think the system is really cool to study. It wasn’t necessarily the disease, but the science around the disease that I found fascinating and the fact that it could really help people one day was a bonus.”
Catie Scull at the University of Michigan in the lab of Professor Nils Walter as a Michigan Life Sciences Postdoctoral Fellow.Scull joined the lab of Dr. David Schneider early on in her graduate studies because she loved the different types of research conducted in his lab. Since joining, she has explored everything from cancer research using cell cultures to purified systems using protein dynamics and kinetics. She spent a large part of her doctoral student career studying a protein called RNA Polymerase I, also known as Pol I. This protein makes the ribosome, and it is a potential target for cancer therapy, Scull said.
“The idea is that if we can decrease the number of ribosomes in cancer cells, then we can decrease their protein synthesis and that will inhibit the cell growth,” she said.
She initially executed studies on actual inhibitors of ribosome synthesis and those studies resulted in one published paper with a second paper currently in submission.
In these studies, Scull studied the rate at which Pol I synthesized ribosomal RNA by looking specifically at the changes that can be made to the polymerase to alter the rate of RNA synthesis. To do this, she grew cells in cell culture and used different techniques to measure ribosomal RNA levels in the cell. Scull then perturbed those RNA levels with potential therapeutic inhibitors to observe their effects on cell growth and viability.
Scull also executed a number of studies on the fundamental properties of Pol I while she was in graduate school.
“I take the polymerase, give it DNA and watch as it synthesizes RNA,” she said. “Then I give it a radioactive nucleotide, which allows me to visualize the process. So far, I’ve mostly just made changes to the polymerase, like getting rid of parts of the polymerase or changing parts of the polymerase from one thing to another, to see how that impacts the rate at which it adds nucleotides. When we change different parts of the structure, we can see how those parts contribute to the polymerase’s activity – how fast it goes, how well it binds to the DNA or how good it is at reading the DNA and making the right RNA.”
Scull’s overall goal is to understand the biological system. People and all eukaryotes have three Pols, but prokaryotes, like E. coli, only has one. Why? Scull said it turns out that the three Pols have specialized roles.
“So now, the question is how are they different, what implications does that have on the way they work and what does that mean for human health and different diseases that involve the three polymerases?” Scull said. “And, in the case of using it to inhibit cancer growth, how can we specifically target this Polymerase I versus inhibiting the other two?”
By the time Scull graduated, shepublished five papers, four primary literature studies and one review, and was first author on all of them. She currently has two additional first-author manuscripts in submission for publication. She has also presented at numerous conferences, seminars and poster sessions, and this year was awarded UAB’s Samuel B. Barker Award for Excellence in Graduate Studies.
Scull interviewed for postdoctoral positions at major scientific institutes around the country, and ultimately decided to pursue a position in the Department of Chemistry at the University of Michigan in the lab of Professor Nils Walter as a Michigan Life Sciences Postdoctoral Fellow. In the lab of Nils Walter, Scull will investigate RNA folding dynamics at the single-molecule level using cutting-edge technology. She believes a postdoc is a good time to branch out and explore somewhere new, but Scull said she would love to come back to UAB as a faculty member when she finishes her fellowship.
While Scull has been incredibly productive and successful as a graduate student, it was not without its challenges. She said her two biggest obstacles were public speaking and learning how to deal with negative data.
“Confidence is the one thing that graduate students have to learn,” she said. “The ability to take constructive criticism and not take it personally. You can’t take your science personally. I’ve had to overcome. All students have to overcome. Imposter Syndrome is real. There have definitely been times that I felt I didn’t belong in graduate school, but I just focused on the scientific questions and why I’m here and why it’s fun and the other stuff gets less scary.”