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July’s faculty member of the month is Nobel laureate Joachim Frank. In 2017 he was awarded the Nobel Prize in Chemistry along with Richard Henderson and Jacques Dubochet for their pioneering work in cryogenic electron microscopy, a visualisation technique where a biological sample is cooled to extremely low temperatures of -150 °C.

In this Q&A, we go back to October 2017 to talk about the day the Nobel prize winners were announced. Among the celebrating and the press engagements, Joachim still found the time to write a Prime recommendation for an article about the very technique for which he was awarded.

Tell us a bit about your work

I am a Professor of Biochemistry and Molecular Biophysics and of Biological Sciences at Columbia University. My lab has developed techniques of electron microscopy and single-particle reconstruction of biological macromolecules. We have used these visualisation techniques to explore the structure and dynamics of the ribosome during the process of protein synthesis.

The Nobel prize is my latest honour for our contributions to the development of cryogenic electron microscopy of biological molecules and the study of protein synthesis. This is in addition to the 2017 Wiley Prize in Biomedical Sciences with Richard Henderson and Marin van Heel, and the 2014 Franklin Medal for Life Science.

What triggered your interest in research?

I think I was born a scientist as I developed a great interest in the natural world around me early on. Even as an eight-year-old I performed “experiments” with tar, carbide, water, coal, gasoline, and any other reagents I could get my hands on! Later, I dissembled and assembled radios in the attic of my parents’ house.

I don’t recall a role model as such, although I do need to give credit to my physics teacher in high school who was able to inspire me and others in my class with his very vivid lectures and demonstrations.

Please tell us a little about cryo-electron microscopy and your involvement in its development for which you received the Nobel Prize in Chemistry 2017.

My involvement preceded the “cryo” part of the technique. At the time, molecules were imaged in the Electron Microscopy at room temperature using negatively stained, air-dried samples.

My aim was to develop a method for reconstructing biological molecules from projections of single (i.e.unattached, not bound in a crystal) particles in random orientations. In this way, the entire angular range could be covered by a relatively small number of low-dose micrographs, each containing hundreds of projections.

This was in sharp contrast to the prevailing view that structure determination of any sort by electron microscopy required crystals (helical, icosahedral, planar 2-D). To realise this idea, a number of problems (such as how to determine the view angles) needed to be solved by mathematical and computational approaches. The first 3D reconstruction by single-particle methods was published in 1986 – a negatively stained ribosomal subunit from E. coli.

Just about at that time Jacques Dubochet’s cryo-preparation method became widely available, enabling my group and others to apply the single-particle methodology to molecules embedded in vitreous ice.

What were you doing on the day you received the announcement about the prize?

I was asleep at 5:18 am when the call came in. I immediately recognised the Swedish accent of the person who called me, and my heart took a jump. I told my wife, and we were both speechless and close to tears for a while.

One of my former postdocs called immediately after the press announcement at 6 am. He had been up all night, convinced that I would be named.

Less than an hour later the first journalist photographers from the Associate Press and Reuters arrived in the lobby of our apartment building, asking for the opportunity to take photographs of me and my wife with our dog Daisy. These are all over the internet now.

Please tell us about the article you recommended on that day in F1000Prime?

I recommended the paper by Loveland et al in Nature on that particular day since, in all honesty, I had intended to do this for some time, and realised that I better hurry up as I knew I would be extremely busy in the days following the Nobel Prize announcement.

I picked the paper as it demonstrated how far we can go now with cryo-EM in deciphering the process of tRNA selection on the ribosome – a problem I had been working on for some time in collaboration with Mans Ehrenberg and Suparna Sanyal in Uppsala.

In fact, we obtained very similar results but were not quick enough to publish them last year. Meanwhile, our own paper has been published with a slightly different spin in the journal Nucleic Acid Research (Fislage et al.).

What I found exciting is that we can see the constellation of the bases engaged in tRNA recognition very clearly, and are now able to put together a narrative of the entire process of decoding. Both papers exemplify the power of cryo-EM in depicting a molecular machine in multiple states at resolutions that allow high-fidelity atomic modelling.

What career advice would you like to pass on to early career researchers?

If you have a sound idea you firmly believe in, don’t give up. Also, peripheral vision is important. In my experience, opportunities often come from nowhere, from outfield, but you need to keep your eyes wide open to recognise them.