The Nobel Prize in Chemistry 2017: Cryo-Electron Microscopy
by Zoe Smallwood, PhD student. Originally published in issue eight of Resonance.
Last year's Nobel Prize in Chemistry was awarded to three scientists who pioneered the work of Cryo-Electron Microscopy (Cryo-EM). Jacques Dubochet from the University of Lausanne, Joachim Frank from Columbia University and Richard Henderson from the MRC Laboratory of Molecular Biology in Cambridge were awarded the 2017 prize for using the technique for revolutionalising the way we image biomolecular structures in solution.1,2
Until the development of Cryo- EM, biochemists were faced with difficulties in actually observing what processes occurred in proteins, DNA and other biomolecules. Electron microscopy was often used, but required harsh conditions which can cause irreversible damage. X-ray crystallography provides high structural resolution with less risk of sample damage, but some biomolecules do not form in a crystalline state. As well as limiting the number of molecules that can be studied crystallographically, the requirement for single crystals often necessitates isolation from the systems the molecules are being studied in, meaning it can be difficult to study some heterogeneous structures as they exist in nature.
The Laureates' work provides a compromise between these two techniques. Cryo-EM provides extremely high resolution (the current record standing at 1.8 Å3) without the need to remove samples from their environment, attempt crystallisation or place them in damaging conditions. Water is a key part of biochemistry, but the vacuum required for conventional electron microscopy often removed water incorporated within structures. This can lead to inaccurate results or different structures than would be observed in situ. Cryo-EM overcomes this thanks to the work of Dubochet, who realised that first firing the sample through a sample of ultracold (−190 °C) ethene did not make the water freeze into single crystals of ice, but instead became vitreous (non-crystalline).
Not only is this closer to the naturally observed state in biological systems, vitreous water barely diffracts the electron beam and so provides much clearer images than if ice crystals were present.2,3 The technique has revolutionised the field of biomolecular imaging, and has been used in high resolution characterisation of important biomolecules such as the Zika virus.4
It has even been predicted that as Cryo-EM advances, it will overtake X-ray crystallography as the preferred method of structural characterisation of biomolecules.5 Whilst crystallographic biomolecular imaging is not obsolete, the development of Cryo-EM has been dubbed “the beginning of a new era in molecular biology”, and the awarding of last year’s Nobel Prize reflects the great potential of the technique for the future.6
- The Development of Cryo-Electron Microscopy, The Royal Swedish Academy of Sciences
- Chemistry World, November 2017, 15-19.
- A. Merk, A. Bartesaghi, S. Banerjee et al., Cell, 165, 2016, 16998-1707.
- D. Sirohi and Z. Chen et al., Science, 352, 2016, 47-470.
- E. Callaway, Nature, 525, 2015, 172-174.
- W. Kühlbrandt, Science, 343, 2014, 1443-1444.
University of Sheffield unveils revolutionary multi-million pound electron microscope
Earlier this year, the University of Sheffield’s new multi-million pound Cryo-Electron Microscopy facility was officially opened by Nobel Prize winner Dr Richard Henderson.