03:43pm Saturday 19 October 2019

A step forward in understanding muscle diseases

How does the ryanodine receptor help us move?
Rouslan: Every single moment of our life depends on the reliable functioning of muscles. Even a slight malfunction of muscles results in diseases. Muscular contraction is initiated by the release of calcium ions from the sarcoplasmic reticulum, the intracellular calcium reservoirs. This process is mediated by ryanodine receptors, a calcium release channel. The mechanism of the release has remained enigmatic for nearly thirty years.

What was – from a technological point of view – the most challenging aspect of this project?
The major technological effort was the necessity to keep up with rapidly developing technology in
electron microscopy. We used single particle cryoelectron microscopy, a method that allows visualizing individual protein complexes frozen in a thin layer of amorphous ice. The electron detectors that are critical for successful determination of the structure have undergone revolutionary changes in the last couple of years. Current technology allows for achieving significantly higher resolution of 3D structures. These developments also stimulated others to reveal the structure of important proteins, with increased competition as a consequence.

You started this work at Max Planck and finished it at VIB. What are the challenges for continuing with a project when changing labs?
Looking back, I think it was totally crazy. Moving to VIB, I had a chance to start my independent lab, which also meant that nearly everything had to be done from scratch. This is an interesting and very rewarding experience, but time consuming as well. I had to spend a lot of time ordering equipment, hiring people, and doing paperwork. Limited funding also meant that I had to build some equipment myself and use old devices that had to be repaired. All these issues seriously distracted me from the research project and we were lucky not to lose to the competition.

How is the collaboration with your former colleagues? Will you continue collaborating on
specific projects?
Since I started the cryo-EM lab nearly two years ago, I discovered that there is a huge interest in single particle EM in the Belgian community of biologists. Therefore, today I’m saturated with collaborations with many Belgian groups. I do keep contact with my former colleagues and it is very likely that in the future we will have common projects.

Was collaboration important for the success of your project?
Yes, we had a fantastic collaboration with our colleagues from ETH. At some point we realized that
to complete data analysis we needed additional mass spectrometry data. We contacted the Ruedi
Aebersold Lab at ETH, which specializes in mass spectrometry combined with chemical cross-linking. They got interested in our project and managed to perform experiments and data analysis for us very quickly. It was an unusual collaboration, as we never met in person and communicated only by e-mail and phone, but it worked out extremely well.

Efremov, et al.
Nature, 2014


    Rouslan Efremov Lab

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