In 1999, young undergraduate Corrie daCosta sat in a lecture hall at uOttawa, as Professor John Baenziger introduced him to the fascinating world of protein structure and function. Inspired by the course and eager to explore the field further, daCosta went on to pursue a PhD under Professor Baenziger’s supervision, eventually becoming the Professor daCosta we know today in the Department of Chemistry and Biomolecular Sciences.
The two researchers stayed in touch over the years (Professor Baenziger even attended Professor daCosta’s wedding!). Yet neither could have predicted that their longstanding friendship would one day lead to a groundbreaking research collaboration.
New insights into how proteins move
Professors daCosta and Baenziger both study the muscle-type acetylcholine receptor. The receptor is the protein that converts chemical signals from nerves into electrical signals that trigger muscle contraction. Without it, our muscles wouldn’t receive the instructions they need to contract.
Professor daCosta studies the function of this protein, while Professor Baenziger specializes in its structure. Through single-molecule particle imaging, Professor Baenziger’s lab was able to capture the acetylcholine receptor in an intermediate state, where the protein was changing from one form to another.
Recognizing the significance of this finding, Professor daCosta and his team conducted single-molecule experiments of the protein to model how the protein operates and transitions through these intermediate states.
By joining forces, the team was able to challenge a long-held assumption about how the acetylcholine receptor works. For over 50 years, scientists believed that the protein’s parts all moved simultaneously in what’s known as a concerted movement. But professors daCosta and Baenziger’s findings suggest that the different parts of the protein move independently as it changes shape to trigger muscle contraction.
“Rather than all the dominoes falling at once, it’s as if one domino falls and then the next. We were able to see a state where one domino had fallen, and the other one hadn’t fallen yet. That proved that the dominoes fall in a sequence.”
The research brought together an international team, including Drs. Hugues Nury and Eleftherios Zarkadas at the Institute of Structural Biology in Grenoble, France, whose state-of-the-art cryo-electron microscopy was essential to the study.
Professor daCosta also mentions the crucial contributions of Dr. Mackenzie Thompson, uOttawa graduate and postdoctoral researcher at University of California, and Dr. Christian Tessier, postdoctoral researcher at uOttawa.
“Mack really drove the structure side, while Christian developed the functional aspects. Unifying the two was extremely rewarding for everyone, and allowed us to learn something that neither side could have figured out on their own.”
From scientific discovery to medical impact
This discovery could improve our understanding of how drugs affect transitions between these states, which could help us better treat congenital myasthenic syndromes.
Congenital myasthenic syndromes significantly affect one’s quality of life, causing issues such as motor delays and muscle weaknesses.
“Understanding how the protein works should allow us, in theory, to better target and control its functions so that we can treat and alleviate disease,” says Professor daCosta.
A science family
While this research is very impressive in terms of scientific impact, what Professor daCosta keeps returning to is the humanity behind it all.
The opportunity to work with his mentor is something he truly cherishes. Professor daCosta jokingly describes their collaboration as a family reunion.
“I see him as my science father and my students see him as their science grandfather.”
After first sitting in Professor Baenziger’s classroom as an undergraduate student, Professor daCosta himself is not only advancing our understanding of an essential protein but also demonstrating the lasting impact of mentorship in science.