Understanding what causes disease is like putting together a puzzle; you have to understand how the smallest parts fit together before the whole picture can be seen. Dr. Julia Guegueniat's research wants to understand the big picutre of how diseases interact with human cells on the molecular level, which requires her to piece together truly microscopic puzzle pieces: RNA.

What is RNA? Along with DNA and proteins, ribonucleic acid (RNA) is one of three major biological “macromolecules” that are essential to life. All three have distinct roles in the reproduction of cells. DNA is the blueprint, containing all the genetic information the cell needs to grow. Proteins are the builders, the ones in charge of constructing the cell according to DNA’s blueprint. RNA, then, is the project manager. It looks at the blueprint, copies that information, and assigns specific jobs to proteins which then carry out their assigned task.

In the past few decades, scientists discovered that RNA, rather than simply copy and paste, makes key modifications to the blueprint before assigning protein jobs. These modifications are common in all organisms, though currently, scientists are unsure what exactly these modifications do. However, scientists like Guegueniat are aware of what happens when these modifications are absent. Cells produced without these modifications contribute to the development of diseases within humans, such as cancer or intellectual disabilities. Understanding what these modifications are and why RNA makes them have become the driving questions of Guegueniat’s research.

As stated at the beginning, Guegueniat wants to see the big picture of how disease interacts with human biochemistry on the molecular level. She's currrently involved in three connected projects, each of which will help piece this puzzle together. Firstly, she’s investigating the specific function of the human protein that is responsible for intellectual disabilities and RNA modification. Secondly, she wants to determine when RNA modifications occur during the life cycle of the cell. Third and lastly, she wants to develop and implement new sequencing technology to detect RNA modifications. All of these puzzle pieces contribute towards both understanding the complete picture of how disease takes hold in humans, as well as how to develop more effective vaccines: “Basically, to solve a big mystery, you sometimes need to look for the smallest detail possible, and then integrate these details to understand the bigger picture: it’s like, putting together a large puzzle.”

In addition to her research, Guegueniat also supervises students in the lab, where she encourages them to ask small, unassuming questions in order to reach the answers to larger questions. “In our lab, I am trying to create a dynamic, safe, and communicative work environment. I want everyone to be able to ask questions and know that there is no such thing as a small or stupid question. 95% of the time, the questions started with “Sorry to bother you, but I have a small/little/stupid question”. I like to first let them know that they are not bothering me, and there is never a small stupid question, it is simply a question. I am here to do some research, but our group is part of the ARRTI; a research and teaching institute, thus helping and answering questions is a part of the process. Communicating and sharing knowledge is important in research.”

Dr. Julia Guegueniat is a postdoctoral fellow in the U of L’s Department of Chemistry and Biochemistry, under supervision of Dr. Ute Kothe. As of September 2020, she holds the NSERC CREATE postdoctoral fellowship in RNA Innovation.