Trending Science: Cryo-electron microscopy captures life molecules and the Chemistry Nobel Prize
The 2017 Nobel Prize for Chemistry has gone to three scientists for their lasting work in the cryo-electron microscopy (cryo-EM) field. The imaging techniques mark a significant breakthrough in atomic structures and biochemistry.
Jacques Dubochet, Honorary Professor of Biophysics at the University of Lausanne, Joachim Frank, a professor at Columbia University and Richard Henderson, a scientist and professor at the MRC Laboratory of Molecular Biology in Cambridge, were awarded the Nobel Prize in Chemistry. They have been recognised for ‘(…) developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution’.
Decades of groundwork before atomic resolution in 2013
The first analysis of biological molecules used traditional microscopic techniques which revealed little about the dynamics and atomic structure of proteins. It was impossible to examine living cells under electron microscopes as scientists feared electron beams would destroy fragile biological material. The other method, using X-ray crystallography could only be applied to the study of rigid state samples.
Between 1975 and 1986 techniques evolved. Joachim Frank made the technology generally applicable by developing an image processing method which merged the electron microscope’s 2D fuzzy images into a clear 3D model. In the early 80s, Jacques Dubrochet was responsible for developing a method of rapid freezing, helping biomolecules retain their original shape. Professor Dubrochet was also part of the EU-funded 3D-EM project (2004 - 2009), which received EUR 10 million of EU funding, focusing on the development of new electron microscopy approaches for studying protein complexes and cellular supramolecular architecture.
In 1990, Richard Henderson revolutionised the cryo-EM technique with better detectors for electron microscopes and better software to analyse the images and provide a 3D image of a protein at atomic resolution. Professor Henderson was also part of the EU-funded INSTRUCT project (2008 – 2011), which received EUR 4.5 million of EU funding towards the building of infrastructure for structural biology studies.
Since then, the electron microscope’s resolution has been optimised and radically improved moving from showing shapeless blobs to visualising proteins at atomic resolution.
The sky’s the limit
Cryo-EM can now allow scientists to explore all structures in atomic detail that were previously invisible to the human eye. From 3D images on the enzyme which produces the amyloid of Alzheimer’s disease to the surface of the Zika virus. Scientists can even now put together film sequences of biological processes as they unfold through capturing snapshots of the same system at different time-points.
The Nobel Assembly at Karolinska Institutet explain their choice and its overall significance to mankind:
‘A picture is a key to understanding. Scientific breakthroughs often build upon the successful visualisation of objects invisible to the human eye. However, biochemical maps have long been filled with blank spaces because the available technology has had difficulty generating images of much of life’s molecular machinery. Cryo-electron microscopy changes all of this. Researchers can now freeze biomolecules mid-movement and visualise processes they have never previously seen, which is decisive for both the basic understanding of life’s chemistry and for the development of pharmaceuticals.’