Last week, the Nobel Prizes for 2017 were announced. The Chemistry Prize went to three scientists for what Scientific American termed “Capturing Proteins in Action”. But why is this important? Especially for the Chemistry Prize? Proteins are the realm of biology, no?
A protein which can detect pressure changes in the ear, allowing us to hear. © Johan Jarnestad/The Royal Swedish Academy of Sciences
Well, yes, proteins are critical in biology. Humans, animals, and plants are made of them, They are the building blocks of life. But proteins are also just big and incredibly complex molecules that each perform a particular role in a whole host of chemical reactions. And what goes on in living organisms if not chemical reactions?
Proteins are essentially really long chains of amino acids all joined together. Because they are such long chains, they fold up (think about spaghetti – it doesn’t stay in long straight bits of pasta once you’ve cooked it – it folds up; although unlike proteins, it folds randomly). How proteins fold is really important, because it determines the physical shape they have, and that in turn governs what they do in chemical reactions. Take a piece of paper – that same bit of paper could be folded into a plane, or a bird, or a cup, and each of those shapes can do something different. There are some theories that the avian compass (the way birds know which direction to fly in when they migrate) is to do with tiny pockets of magnetism in a protein responding to the Earth’s magnetic field, making the protein fold differently, and causing a very slightly different chemical reaction to happen. This in turn sets off a chain reaction of events eventually ending with the bird knowing which direction to fly in.
So knowing what proteins look like is really important to understanding how they function. Not just which bit of a reaction they are involved in, but what exactly they are doing. This information could be incredibly useful in a lot of different ways.
- Understanding exactly what is happening in a whole range of biological processes.
- Development of better and more accurate drug therapies and cures for diseases, which are able to target very specific processes.
- Solving a lot of the sustainability issues in society, by producing new (better) materials, by working out how to speed up the breakdown of materials, by finding new ways to recycle more materials more efficiently…
- Analysing things like the proteins which cause antibiotic resistance, and the surfaces of viruses
- Modelling and predicting (with a much higher degree of accuracy) interactions between proteins and other chemicals.
The Zika virus. © Johan Jarnestad/The Royal Swedish Academy of Sciences
But working out what proteins actually look like is really difficult, because they are so huge.
NMR spectroscopy (at its most basic, a technique which uses magnetic fields to get information about atoms in a molecule, usually the hydrogen atoms, which scientists can then use to work out the structure of the molecule), while a really powerful technique for smaller molecules, just produces too much overlapping data to be useful for all except the smallest proteins; it also can’t really give any information about the physical 3D structure – which is, of course, super important.
X-ray crystallography has long been the main way scientists have worked out the 3D structure of proteins, and it has been a really useful tool, providing far more information than we’ve ever had before. It has its drawbacks though, mainly that you need to crystallise the protein. Some proteins are very difficult (or impossible!) to persuade to form crystals, and even if you can get a protein to form a crystal, there is no guarantee that its structure in crystalline form is the same as its structure in solution. (Think about sugar, C6H12O6, and all the different forms it can be found in: its properties can vary hugely, and that is only a very simple molecule!) It is also almost impossible to crystallise it partway through a reaction.
Electron microscopy has also proved useful over the years, as it provides an image at the atomic level. However, it can only be used for studying dead matter: the beam is so powerful it destroys biological molecules.
So this year’s Nobel Prize for Chemistry has gone to Jacques Dubochet, Joachim Frank, and Richard Henderson, for something which is exciting and really seriously useful. A technique which allows us to view proteins actually in solution, as they are in nature. It’s called cryo-electron microscopy.
Henderson modified the electron microscope, making it weaker, and taking pictures from a number of different angles, to image biological matter. Frank developed mathematical and computational techniques to be able to merge a number of 2D images into a single 3D image. However there still remained one problem: liquid water will evaporate under the conditions of electron microscopy, and without the water the protein collapses. Freezing the water introduces ice crystals which disrupt the beam of the electron microscope. Dubochet solved this problem by developing a method for vitrifying water – freezing water so quickly it remains completely transparent, like glass (vitrifying from the Latin ‘vitrum’, literally ‘glass’). Put the three together, and suddenly proteins we have never before been able to image can be viewed in 3D at the atomic level. Snapshots can be taken in the middle of reactions. There are endless possibilities for new understanding of how processes we already know about actually happen. And that’s before we look to future applications.
Imaging may be some of the nuts and bolts of chemistry, something that is learnt about even in schools, and not often thought of as cutting edge or new. But as this year’s Nobel Chemistry Prize shows, it is crucial to everything else that goes on in chemistry – and in biology and medicine too.
Improved techniques allow much better resolution – now right down to the atomic level. © Martin Högbom/The Royal Swedish Academy of Sciences
In the classroom:
Nobel Prizes are always a good thing to talk to students about, and this can be accessed at multiple levels depending on your students. Even younger students can see that you can fold a piece of paper in different ways, and even small changes can have big effects (you can even get your students to each fold a small aeroplane from a piece of paper, and compare how they fly and how far they go to illustrate this point about small changes in shape having potentially big consequences).
For older students, it could be linked to a number of things: earlier work in a similar field, and the Nobel Prize awarded for the structure of DNA; how enzymes function; vaccination and immunity. This is also a good opportunity for some wider scientific reading. There is a lot of news coverage of the Nobel Prizes, but it is also cutting edge science.
All A-level students should be able to see the interplay between the different sciences in achieving a breakthrough which is important to all of them. Depending on their interests they may prefer to look at any of the myriad future applications of the discoveries we will be able to make, or the imaging technique itself; regardless it is a good opportunity for some properly written up and referenced research towards their practical skills assessment.