Behind every scientific achievement and publication lie the stories of the scientists who took part in the work. Learning about these stories is not only inspiring, but it is also crucial to understanding that scientific facts and figures have a human dimension to them, which in part determines the process of research.
Erin Duffy works as a graduate student at Professor Matthew Simon’s lab on West Campus. Earlier in September, Duffy and her colleagues published their paper in Molecular Cell on a new method of detecting RNA molecules characterized by a special type of nucleotide. Their method cleverly makes use of chemistry knowledge and improves upon previous ineffective approaches.
In recent years, scientists have found that non-protein-coding RNAs, known as noncoding RNAs (ncRNAs), are just as critical to cell regulation and function as RNAs that code for proteins. The exact roles of these ncRNAs, as well as the mechanisms of their functions, are still mostly unknown. And so they have captured the interest of many biologists, including those in the Simon lab.
The production and degradation dynamics of RNA molecules in cells is of particular interest, as it reveals in what ways they interact and how they are regulated. Duffy’s work focuses on a technique to label, capture, and track RNAs that contain a specific type of modified base, called 4-thiouridine (s4U). Unfortunately, when her team attempted to use a method already published in the scientific literature in order to capture these RNAs, she was frustrated by months and months of fruitless results.
“I kept doing these pulldowns, day after day after day, and we weren’t seeing anything,” said Duffy. “I doubted myself a lot more in the beginning. It took us a long time for us to step back and look at the chemistry.”
A Eureka moment
The breakthrough happened when Simon and Duffy found the chemistry of the method to be rather problematic.
“I remember it very clearly—it was in March, and I was sitting in Matt’s office, and I brought another blank gel to his office…It was a full six months of blank gels,” said Duffy. “We started drawing structures on the board, and looked at all the structures we drew next to each other.” The original method in literature features a disulfide exchange reaction that results in a product that is more reactive than the starting molecule, causing the reaction to be highly unfavorable in equilibrium and very slow.
After recognizing the potential issue, they started working to find a better way to study these RNAs. To improve the method, they substituted the reagent HPDP with methanethiosulfonate (MTS), a different molecule that reacts readily to form a more stable product. This results in a significantly more favorable reaction in equilibrium, with a nearly complete conversion. After a long series of experiments, the modified method demonstrated a marked improvement and was shown to be able to detect different RNAs effectively.
Duffy emphasized the collaborative element of the work. Professor Simon was the main driver behind the paper. “He was the first one to recognize the problem with the chemistry,” said Duffy. Michael Rutenberg-Schoenberg brought the bioinformatics expertise to the team. Rob Kitchen and Mark Gerstein provided the crucial pipeline to analyze microRNAs in the later part of the project.
Apart from faculty, researchers, and graduates, an undergraduate, Catherine Stark, also plays a very important role in this project and was also an author on the manuscript. “Catherine and I were learning together at that time,” said Duffy. “And she definitely had more expertise in the biology and the actual bench-work, and could say ‘I’m confident in this experiment, I’m not confident in this one,’ in a way that the rest of us could not.”
This paper not only underscores the power of collaboration in science, but also highlights the interesting interface of chemistry and biology. While studies that draw methods and knowledge from both biology and chemistry would often have a closer emphasis on either the biological or the chemical side of the topic, this paper sits nicely between the two. “A lot of people have thought very carefully about the biology side of this method, but not as much about the chemistry side,” said Duffy. In this paper, the close chemical analysis of the molecules used is nicely coupled with the biological significance of the results, such as the data on various microRNAs in the cell.
Outside the lab
When she isn’t doing important work in the lab, Duffy fills her time with other diverse pursuits. Duffy has an Irish background (incidentally, her first name, “Erin,” means “Ireland”). Bearing the family crest on her wrist, she identifies with Irish culture, and spends much of her free time on Irish dancing, sometimes participating in Irish dancing competitions and events, such as the World Irish Dancing Championships.
Apart from being a talented and meticulous scientist, Duffy also works to increase women’s presence in science. She works closely with Women in Science at Yale (WISAY), and this year serves as a mentor for new graduate students.
“I think we definitely need more women in science. There is no question. And we need more women that stay in science,” said Duffy. Duffy discusses the concept of “confidence gap” between women and men. She notes that in every stage of science, men generally tend to doubt less about themselves than women do, even though both parties are just as capable, and this really inhibits women in science.
“There are thirty something faculty in MB&B, and four of them are women. This is ridiculous. And it’s not just here.”
“We need to stop this disproportionate amount of women leaving [science],” said Duffy.
Peter Wang is a sophomore at Timothy Dwight College. He is also an undergraduate researcher at the Simon Lab. Contact him at firstname.lastname@example.org.
(Featured image courtesy of Erin Duffy.)