Standing on the shoulders of… Dorothy Hodgkin

On the way to work last Wednesday, a story on BBC Radio 4 – ‘Today programme’ suddenly grabbed my attention: “February will mark the 100th anniversary of women having the right to vote!”

Curiosity sparked, I turned up the radio: “BBC Radio 4 are holding an online vote for the most influential British women of the past century. Each day in the run up to the anniversary we’ll be shortlisting and celebrating a candidate for the award”.

Last Wednesday’s nominee was Dorothy Hodgkin, the only British woman to ever win a Nobel Prize in the sciences. Dorothy won her award in 1964 for developing a technique that enables the complex structure of proteins to be deciphered – this is known as protein crystallography. Dorothy used this technique to work out the structure of insulin, vitamin B12 and penicillin.

Funnily enough, I had recently been discussing this technique with my colleague Jessica. I told her the news story when I got to work and we decided we’d share with you how, thanks to Dorothy’s brilliant work, protein crystallography is currently helping researchers funded by the MND Association to find out more about MND.

A brief overview of protein crystallography

Crystallography allows researchers to work out the structure of large molecules. Initially, the technique was just used to work out the structure of chemical substances such as diamonds or sodium chloride. However, Dorothy developed the technique further so it could be used to investigate biological molecules as well. Protein crystallography can even be used to work out the structure of several proteins attached together, something known as a ‘protein complex’.

How does it work?

First, the protein the researchers want to know the structure of is crystallised and a beam of x-rays is then shone through the crystal. The scattering of the beam, known as the diffraction pattern, is analysed by a computer to show the shape and structure of the protein or protein complex.

protein crystallography diagram

Diagram of protein crystallography

Why is crystallography useful in MND research?

There are several faulty proteins that play a key role in MND. These proteins interact differently with other molecules in motor neurones and their behaviour in protein complexes is also altered. Working out the structure of faulty proteins or protein complexes using crystallography can reveal the differences between the faulty and the ‘properly functioning’ proteins. In other words, crystallography can help show us what is going wrong in people with MND that have these faulty proteins.

As well as this, crystallography can be used to see if two specific molecules can become attached together. This is very important for testing if a potentially therapeutic compound can attach to a faulty protein found in MND. Let me give you an example.

How our researchers are using crystallography

toxic clusters in neuron 2

Professor Samar Hasnain’s team at the University of Liverpool is studying a protein called SOD1. Faulty versions of this protein cause 20% of inherited cases of MND. In these patients, the faulty SOD1 proteins don’t interact properly with other important proteins in the cell, resulting in the SOD1 protein forming damaging toxic clusters in the motor neurones.

Using crystallography the team has identified two compounds that can bind to an exposed part of the SOD1 protein to stabilise it, as they suspect this will prevent formation of toxic clusters. The team is now investigating whether, by stabilising SOD1, these compounds can prevent clustering and could therefore be used as a potential treatment for MND.

To sum up, protein crystallography, a technique introduced by Dorothy Hodgkin to help us study the structure of proteins, is still proving incredibly useful in research today and is helping us identify possible ways we could treat MND.

Another nominee for the BBC competition

Interestingly, another female scientist, Rosalind Franklin, who was also in the running for the BBC vote, used crystallography to study the structure of DNA. This was fundamental in the work (and Nobel Prize) of Watson and Crick, and has led to great developments in understanding and hugely significant breakthroughs in recent times.

Read more

You can read more about crystallography on some of our previous blogs:

You can also read more about Dorothy Hodgkin and her work on crystallography here.

This article was written collaboratively by Nick Cole, our Head of Research, and Jessica Sturgess, our Supporter Information Officer.