After years of ongoing experiments and an extended review process, the teams of Thomas Voets (VIB-KU Leuven Center for Brain & Disease Research) and Joris Vriens (KU Leuven) have successfully published a boundary-pushing paper on mammalian heat-sensing channels in the high-impact journal Nature. The researchers are credited with a hot discovery: the presence of three redundant ion channels in neurons, forming a fail-safe heat-sensing mechanism for extra burn protection. It took plenty of commitment – and sometimes 80 behavioral mouse experiments per day – but all the hard work has paid off for Thomas and team members Ine Vandewauw, Katrien De Clercq and Marie Mulier.
Despite the fact that pain signaling neurons in mammals have been identified for more than a century, the molecular mechanisms that make them work are poorly understood. Using mouse models, the team successfully deactivated several known molecular heat sensors, but there was no loss in heat-sensing ability.
It was only by creating a triple knockout mouse strain lacking three specific ion channels that a complete lack of response to pain was shown. This observation demonstrates just how important heatsensing is in mammals, with this triple-redundancy system ensuring that we avoid potential burn sources even if two of our heat-sensing ion channels fail.
Thomas, has anything changed as you finish up your first year at VIB? Any surprises?
Thomas: “The VIB experience has been very positive for me and the lab throughout the year. Although it is only fair to say that my years as a researcher at KU Leuven and the university’s continuous investment in our research has given us a head start. But VIB offers many new opportunities for scientific collaborations and training, direct access to advanced technologies – not to mention a significant increase in the number of emails in my inbox…”
Did publishing in Nature pose any obstacles?
Thomas: “The publishing process was quite a struggle. Although we were confident that we had fully established the central findings of the paper more than two years ago, it took an additional 18 months to convince the referees. As a result, the paper contains an extended supplementary online section – and enough material for one or two more papers. But considering the many positive reactions to our paper from colleagues and the coverage in the press, it was certainly worth it.”
To the rest of the team, what were the most important experiences for you during this project?
Katrien: “I started on this project at the beginning of my PhD. As a result, I learned quite a bit about animal handling and experiments – knowledge that I now use daily.”
Ine: “On my side, this research represents most of my PhD work. In fact, I presented the results of our study during my defense – naturally a key life experience for me!”
Marie: “I came later to the project, and the story of the triple knockout mice had already been shaped. Together with Ine, I worked on a protocol to retrain a specific ion channel in our mouse model. I knew up front that it would be a challenge, but we succeeded!”
Any key challenges that you’d like to mention?
Ine: “For me, the biggest challenge had to do with the skin-nerve recordings. It took me quite some time to set up this technique in our lab, and it took even more time – and a lot of patience – to get good single-fiber recordings. As Thomas mentioned, getting the paper published was a long process, but it was worth it in the end. I learned that patience and perseverance are important for excellent research.”
Katrien: “I completely agree. It takes a huge amount of dedication to publish in a high-impact journal.”
Finally, are there any key takeaways that you’d like to mention?
Marie: “I loved the excitement of successful experiments! The more the reviewers asked for, the more well-documented our story became, and the better we could prove our hypotheses. A few months after publication, I attended an ion channel congress abroad where several keynote speakers mentioned the importance of our paper in their presentations. It’s fulfilling to hear how our story completes the work of other researchers in this field.”
Vandewauw et al., Nature 2018