Assistant Professor of Chemistry and Biochemistry Julia Widom is leading a detailed study on the intricacies of RNA, the body's genetic messenger.
Mapping the Sequence Landscape of RNA Structure, Dynamics and Protein Interactions Using High-throughput Single-molecule FRET
In the heart of the University of Oregon's Chemistry and Biochemistry department, Assistant Professor Julia Widom leads a team of dedicated researchers delving into the complex world of RNA, the messenger that carries instructions to the body’s genetic building blocks—and holds the potential to help shape the future of medicine and technology.
With a passion for understanding how RNA folds into specific structures at a molecular level, Widom's team explores beyond the textbook definitions of DNA and proteins, focusing on the intricate dance of RNA structures within cells.
"We're interested in learning about how RNA folds into specific structures with a very high level of detail," Widom explains. "RNA can perform many different functions, and a lot of those require it to fold into specific structures to be functional."
The Widom Lab employs advanced methods to study biologically important RNAs—particularly those relevant to diseases.
Postdoctoral researcher Satya Yadav examines RNA data in the lab.
“If I look across the research portfolio of my lab, we have people using a lot of different techniques to study a lot of different types of RNA,” Widom says. Some of these RNA systems are very complex, while in some cases “we want to study very small, very simple RNA to try to learn about the most fundamental aspects of why RNA adopts the structures that it does.”
RNA's dual significance in both biology and technology captivates Widom and her team. The COVID-19 pandemic serves as a stark reminder of RNA's role as an information carrier in viruses. RNAs play vital roles under normal conditions, as well, and a deep understanding of this is necessary for effective treatment when things go awry.
On the technological front, the groundbreaking mRNA vaccines, which served as a beacon of hope during the pandemic, trace their roots back to decades of RNA chemistry research. RNA's versatility also extends to creating sensors for tracking molecules in living organisms and laboratories alike.
"RNA can really do a bit of everything, both in living organisms and in the lab," Widom emphasizes.
The Widom Lab is a hive of scientific activity, with four PhD students, one postdoctoral research fellow and two undergraduates actively contributing to various projects. From studying small RNAs to exploring single-molecule dynamics, the team's efforts all contribute to their common goal of deciphering the intricacies of RNA structures.
Widom's most recent project began in fall 2022 after the lab received a $1,805,577 grant from the National Institutes of Health. With support from Satya Yadav, a postdoctoral research fellow, the project focuses on mapping the RNA sequence landscape using single-molecule measurements on multiple RNA sequences simultaneously, a feat made possible by a novel sequencing approach.
Professor of Chemistry and Biochemistry Julia Widom
The goal of this project is to do single molecule measurements on lots of different RNA sequences at the same time. We have a method that allows you to determine the sequence of every molecule.
Julia Widom, professor of chemistry and biochemistry
The project involves single-molecule FRET measurements, a technique based on fluorescence, to track the distance between two parts of an RNA molecule. This method, combined with single-molecule sequencing, allows researchers to correlate RNA behavior with its sequence, providing a more comprehensive understanding of RNA dynamics across various sequences.
"We have made a lot of progress on that technical, methodological side of things," Widom says.
The ongoing research is divided into two main directions, each addressing distinct scientific questions. One direction, led by an undergraduate researcher, delves into the process of RNA splicing. RNA is initially produced in the form of pre-messenger RNA, which contains regulatory sequences that direct the RNA to be cut at specific locations. The focus is on understanding how variations in these regulatory sequences affect RNA structure, providing insights into the inherent variation in these critical sequences.
"The scientific direction we're interested in involves looking at these pre-messenger RNAs," Widom elaborates. "We're looking at how variations in some of these regulatory sequences affect the structure of the RNA."
The second direction, spearheaded by Yadav, aims to unravel the relationship between RNA sequence and the stability of specific RNA structures. This foundational work contributes to the modeling of RNA structures, laying the groundwork for predicting RNA structures accurately across diverse sequences.
"There are so many scientific questions you can answer by understanding RNA," Widom reflects.
