Miller School M.D./Ph.D. Student Finds Success Studying Mitochondrial Messenger RNA
Article Summary
- Miller School student J. Conor Moran is a member of the school’s Medical Scientist Training Program.
- Moran’s interest in basic science research led him to join two Miller School faculty members to study the mechanisms of gene expression in mitochondria.
- The research team focused on mitochondrial messenger RNA, which folds in specific ways in healthy mitochondria.
J. Conor Moran’s interest in basic science has given him a strong foundation as a researcher during his studies at the University of Miami Miller School of Medicine — and led him to coauthor a paper in the journal Science that adds to the fundamental understanding of gene expression in mitochondria.
Medical Scientist Training Program students like Moran earn an M.D. and a Ph.D., sandwiching their doctoral work between the two halves of medical school. In one of his early research rotations, Moran met Antoni Barrientos, Ph.D., professor of neurology and biochemistry and molecular biology at the Miller School.
Moran was drawn to Dr. Barrientos’ work, and Dr. Barrientos was pleased to find a medical student with interest in basic research.
“Medicine does an immense amount of good, but I don’t think people realize how limited the capabilities of modern medicine truly are,” Moran said. “The only way we are going to solve hard problems such as cancer, dementia or aging is by understanding the fundamental processes that govern how living organisms work.”
Mitochondrial mRNA
Barrientos and Flavia Fontanesi, Ph.D. an assistant professor of biochemistry and molecular biology at the Miller School, invited Moran to conduct his Ph.D. research on a complex project they’d been exploring.
Though their research focuses on basic science, it always has some connection to understanding disease, Dr. Barrientos said.
This project involved studying the mechanisms of gene expression in mitochondria, the organelles inside cells that convert nutrients into energy. Dysfunctional mitochondria can cause diseases such as Leigh syndrome, a fatal, genetic childhood neurodegenerative disorder. A better understanding of how mitochondria work is vital to someday curing such diseases.
The research team focused on mitochondrial messenger RNA (mt-mRNA), which folds in specific ways in healthy mitochondria.
Their key finding — the first map of how mt-mRNA folds in human cells — was published in Science in July 2024 with Moran as the lead author.
Building on Existing Biochemical Work
Moran made several important contributions to this research.
While he was still in his first years of medical school, he studied with Silvi Rouskin, Ph.D., an assistant professor of microbiology at Harvard Medical School, who became another collaborator on the project, along with her student, Amir Brivanlou.
Rouskin had developed a biochemical tool for studying the folding of viral RNAs that the researchers wanted to apply to their mt-mRNA research. Because RNA is flexible, it’s difficult to image using biophysical tools like electron microscopy, Moran explained. Adapting and optimizing Rouskin’s technique allowed the researchers to create a dynamic picture of structural changes in mt-mRNA.
“The question of how to adapt the method to mitochondria was not easy,” Dr. Barrientos said. “There was a lot of trial and error, but the perseverance of Conor was fundamental.”
Moran also engineered cells in which a gene for a protein that interacts with mt-mRNA and could influence its folding was removed, known as “knockout” cell lines. The gene is biomedically relevant in Leigh syndrome.
Proactive Problem Solving
Though Moran has since completed his Ph.D. research, his work built a foundation for the team’s further research. Dr. Barrientos has used the knockout cell lines in other studies, leading to three publications in high-profile journals so far.
He and Dr. Fontanesi also praised Moran for his resilience as a researcher, which benefited the whole team.
“He’s a very proactive person,” Dr. Fontanesi said. “If he sees a problem, he’s got to look for a solution.”
Moran will graduate in May. He’s considering a career in clinical pathology: using laboratory techniques to diagnose and treat disease while acting as a conduit between doctors and researchers.
His studies at the Miller School have not only given him the opportunity to learn the language of both medicine and the lab, but also connected him with mentors who have shaped him as a scientist.
“I feel like, as a clinician, you can see a finite number of patients throughout your life, and you’ve helped each one of those people,” he said. “But if you develop a new test or find a way to detect a disease earlier, it could affect tens of millions of people.”
Tags: Dr. Antoni Barrientos, Dr. Flavia Fontanesi, medical education, Medical Scientist Training Program, mitochondrial diseases, mRNA