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.

Research on the road

Spring is in the air, the trees are budding, and the birds are singing. Slowly, hesitantly, the director of research emerges from his office and blinks in the bright spring sunshine, before setting off on his travels to distant parts of the country…

This is branch AGM and Spring Conferences season, which means it’s time for a road trip! It gives me the chance to personally thank people for the incredible support they give and the money they raise for research – and gives me a chance to tell them how we are spending that money on research.

Sunday
First stop, Sunday, in Harrogate. My knee is a bit swollen after an operation over Easter, so my wife volunteers to drive there and back (I think the shopping in Harrogate was an extra attraction… ). The Yorkshire Dales branch supports one of our research projects at Sheffield University, so I focus the talk around that work – on how these incredibly long, thin motor neurones manage to keep their shape, how they need specialised systems to transport essential chemicals up and down the nerve fibres and how this appears to go wrong at the earliest stages of the disease. Things get off to a dodgy start – I’m using a computer and projector, but when I try to put on the first slide the computer keyboard freezes. I can’t even switch it off to switch it on again. Thanks to a member of the audience, we manage to get it working, but there were a few minutes where it looked like I’d be improvising my way through the next hour!

Monday and Tuesday
I spend Monday back in the office, but Tuesday sees a drive up to Blackpool for the Blackpool, Wyre and Fylde branch meeting. This time, I don’t have to set up my gear – the Blackpool Centre for Independent Living has an amazing new system, including a projection screen that I only need to touch to move from one slide to the next. I’m also asked to present two ‘Extra Mile’ awards – it’s such a pleasure to be able to recognise the support that is given by healthcare professionals and others who so often make that special effort to do that bit more, to treat people with MND as people and not ‘statistics’.  Don’t forget, you can nominate those you think deserve recognition for going that extra mile via our website. 

Wednesday
I stay overnight with an old school friend, who lives close by and head to Liverpool the next day. The Merseyside Branch AGM isn’t until the evening, so it’s an opportunity to spend the day meeting up with some of the researchers we fund in the city. We have two clinical projects at the Walton Centre for Neurology & Neurosurgery, so I catch up on progress with the Principal Investigator, Prof Carolyn Young.  Good progress is being made on our project examining the impact of non-invasive ventilation (NIV). In fact, the work emerging from this study has been informing the development of guidelines on the use of NIV for MND, by the National Institute for Health and Clinical Excellence.

It’s then off to the University of Liverpool, to meet up with Prof John Quinn, one of our new grant holders, who is looking for genetic factors that predispose people to develop MND. Unlike ‘traditional’ genetic research, which looks for genes that are altered or mutated, his work involves looking at stretches of DNA which might act like a ‘dimmer switch’, controlling how and when specific genes are switched on and off. It’s mind-blowingly complicated and I come out with my head spinning…

I then get a chance to have a bit of ‘hands on’ work in the lab of Prof Samar Hasnain, who is looking at how the molecular structure of the SOD protein is altered in the SOD1 form of familial MND. These studies will help chemists to design potential drugs that can selectively interact with SOD, reducing its damaging effect. The research itself involves a process called ‘X-ray crystallography’, which uses a massive piece of equipment called a synchrotron. If you’re ever driving along the A34 south of Oxford, you’ll see something that looks like a football stadium, sitting in the middle of the countryside. That’s the Diamond Synchrotron, one of a handful of such places around the world where the high energy X-ray beams needed for this work are generated. The Liverpool research team uses the Diamond resource, but they also use similar equipment in France, Switzerland and even Japan… wherever they can book ‘beam time’ on the equipment.

The other thing you need for this research are protein crystals. One of Prof Hasnain’s colleagues, Dr Svetlana Antonyuk, gave me a quick ‘hands-on’ lesson on crystal growing. She gave me some very easy crystals to start on – apparently these are used as a ‘control’ to check that the various chemicals are OK when growing more difficult proteins. As the photo shows, I managed to get some nice results!

It’s then over to the south side of the city for the Merseyside branch meeting. The branch chairman kindly lets me give my talk before the formal AGM, so I’m heading off down the road to Northampton by 8.30.

Thursday and Friday
A couple of days on the office to catch up with paperwork and I’m off to Cardiff Friday evening, staying the night with an old University friend. I have to read a bedtime story to a 7-year old, which takes me seriously out of my comfort zone!

Saturday
As Kate mentioned in her blog post, the first Association Spring Conference was in Newport on Saturday. I give a presentation on the main strategic themes of our research programme: the need to find causes of MND, develop better laboratory models, get the best researchers working on MND, set up a clinical research base and improve access by scientists to the explosion of new information on the disease that is occurring. I also try to put across the need for international collaboration, not just between the researchers, but also between funding bodies, which is an area I am very keen for us to continue to grow.

There’s not a cloud – or indeed an aircraft vapour trail, thanks to volcanic activity – in sight as we head past Heathrow on Saturday evening, en route to Dartford for Sunday’s Spring Conference.

Sunday
The Sunday event goes well. I give the same talk as in Newport, but it’s a little more polished as it’s the second time around. Part of the presentation includes details on the BioMOx study, a project which we co-fund with the Medical Research Council. The project is seeking to identify biomarkers – a specific ‘fingerprint’ for MND – which will help speed up diagnosis and give us vital information on how the disease progresses. In Newport and Dartford I meet three people with MND who are participating in the study, one of the largest and most comprehensive of its kind in the world. It’s great to hear first-hand the importance people place on being able to take part in research and of the practicalities met when volunteering to go on a study like this.

Back home mid-evening. A busy but very informative and inspiring few days!