2016 – Alexey Amunts

“Alexey Amunts is the recipient of the 2016 Lennart Nilsson Award for his pioneering work in the ongoing “Resolution Revolution”, using cryoelectron microscopy (cryo-EM) to visualize structures of individual proteins.”

Alexey AmuntsAlexey Amunts is head of the Swedish cryo-EM laboratory at SciLifeLab and researcher in the Department of Biochemistry and Biophysics at Stockholm University. Cryo-EM led him and his team to the first visualizations of a protein complex that regulates a cell’s energy budget, the mitoribosome, with extremely high resolution – at the atomic scale.

The method uses a highly focused electron beam to shoot electrons at biological samples, for example mitoribosomes, frozen in liquid nitrogen, at about –200°C. Hundreds of thousands of pictures of a single mitoribosome are combined with the help of computational analysis, and the final result is an extremely detailed three-dimensional model of the original biological structure.

These visualisations provide essential information about structures that govern cellular functions and modes of action. Amunts has spent many years trying to determine the structures of biological molecular complexes, a path on which he started as a PhD student in Israel. While he’d first intended to go to medical school, his path changed when he discovered an interdisciplinary research program at Tel Aviv University. He had his first foray into visualising large molecules or “macromolecules,” looking at a “macromolecular machine” in plants that converts sunlight into energy, photosystem I. Amunts and his mentor, Nathan Nelson, used X-ray crystallography to visualise this macromolecule – the most powerful tool available at the time.

Meanwhile, cryo-EM methods were on the horizon. Amunts moved for his postdoc to the MRC Laboratory of Molecular Biology in Cambridge, UK, where the technique has been evolving. In 2014, he, his supervisor Venkatraman Ramakrishnan (recipient of the Nobel Prize in Chemistry, 2009), and their colleagues Sjors Scheres and Alan Brown were among the first to prove the method could capture such detailed and fine-scaled images of a biological structure, using the mitoribosome as their subject.

Since then, Amunts and his research team have created images of structural features of the mitoribosome that orchestrate the metabolism of cancer cells. The mitoribosome could be a kind of Achilles’ heel for tumors, and a target for therapy. Amunts and his team have gone further with cryo-EM to show the mitoribosome bound to potentially novel therapeutic compounds. They captured the first high-resolution images of a drug bound to mitoribosome, which opens up promising perspectives for structure-based drug design using cryo-EM.

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