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.

Tackling weight loss in MND – from ProGas to PostGas

Swallowing problems are an incredibly common cause of malnutrition and weight loss in MND patients. To add to this, weight loss in MND is associated with shorter survival. This means managing swallowing problems effectively is crucial to ensuring people living with MND can have the best possible quality of life.

Managing swallowing problems using gastrostomy

Swallowing problems in MND are often managed by placing a feeding tube directly into a patient’s stomach – this is known as a gastrostomy. The feeding tube can either be placed into the stomach via the mouth, or directly from outside the body.

An MND Association-funded study that concluded in 2015 provided much needed evidence on the best method and timing for gastrostomy. This study, known as ProGas, was led by Professor Chris McDermott at the Sheffield Institute for Translational Neuroscience (SITraN).

What were the results of ProGas?

Essentially, ProGas found that the method used for gastrostomy didn’t affect patient’s survival after the procedure. However, the greater the weight loss, from diagnosis to the time gastrostomy was performed, the worse the patient’s survival after the procedure.

To emphasise this point, of the patients who’d lost over 10% of their diagnosis weight at the time of gastrostomy, only 4% actually gained weight after the procedure, whereas 82% continued losing weight. Overall, they found that approximately 50% of patients lose weight in the three months following gastrostomy, irrespective of how much weight they lost before the procedure.

Naturally, these results raise questions about how effectively gastrostomy manages nutrition and weight loss. It is possible these results could be due to the natural disease progression. However, they could also be due to variation in symptom management methods after gastrostomy.

Tackling weight loss after gastrostomy

The MND Association has recently started funding a follow up project, known as PostGas, which aims to provide urgently needed evidence-based guidance on the best clinical practice for managing nutrition and weight loss after gastrostomy. This project started in June 2017 and is also led by Professor McDermott’s team at SITraN. One of the researchers in the team, Dr Haris Stavroulakis, recently presented their ProGas findings and introduced the PostGas study at our regional conference in York – you can view Dr Stavroulakis’ talk online.

What is the plan for PostGas?

A detailed survey asking what protocols doctors currently follow and what advice they give to patients after gastrostomy will be given to doctors at 24 specialist MND clinics across the UK. For example, doctors will be asked how they calculate the caloric intake requirements of their patients and what feeding plans they recommend.

Patients will then be recruited and followed for nine months after gastrostomy to monitor changes in factors such as weight and BMI, as well as self-perceived quality of life. These factors will be assessed 3, 6 and 9 months post-gastrostomy. Survival rates after the procedure will also be observed to see if different management methods have an effect on this.

Hopefully, PostGas will provide doctors with evidence-based guidance on how to improve nutrition and limit weight loss in people with MND after gastrostomy. Ultimately, this might extend patients’ survival and improve their quality of life.

It’s not just about the neurones

Long before the latest wave of cellular and molecular biology advances started to give us new information on what was going on at the cellular level in MND, some doctors had observed that if the disease started in one particular part of the body, it would be neighbouring parts that became affected next.  This suggested that the disease usually starts in a single part of the brain or spinal cord before spreading further, like ripples in a pond.

How this happens is not well understood. It is likely that there are a number of processes going on, but they can broadly be divided into two theories. One of these is that damaged proteins can leak out of sick neurons and ‘infect’ their neighbours – a subject we have discussed at previous international Symposia. Continue reading

Catch up on Symposium…focus on causes and treatments

Following on from our previous catch-up blog on clinical management talks presented at the Symposium, here is a continuation that looks at talks focusing on treatment therapies and causes of MND.

RNA Binding & Transport

RNA is the lesser-known ‘cousin’ of DNA – it contains copies of genetic instructions sent out from the nucleus – the ‘control hub’ of every cell. This RNA is carried out of the nucleus by lots of different proteins, including the RNA-binding proteins TDP-43 and FUS, which act as ‘couriers’ dropping off their RNA at the right part of the cell and then returning to the nucleus for the next package.

These binding proteins both play an important role in motor neurone health. In motor neurones affected by MND, the TDP-43 and FUS seem unable to make their way back to the nucleus so they form clumps in other parts of the neurone. How and why this happens is not really understood and several presentations on the first day of the Symposium provided insight into what might be going wrong.  Dr Brian Dickie, Director of Research Development at the MND Association, summarises these presentations in his blog Libraries, Doormen and Harry Potter. You can also hear Brian talk about RNA proteins on the Symposium website. Continue reading

Catch up on Symposium…focus on ‘clinical management’

From abstracts to posters, pushpins to ribbons, it takes a whole year to get to this day – no, not Christmas, but the 28th International Symposium on ALS/MND. In this and the following ‘catch-up’ blog we will summarise what went on at the Symposium and where you can find out more information. To begin with, you can read about what goes into organising the biggest meeting of its kind on our blog:  It’s that time of year again … #alssymp.

Because of the diversity of the talks presented at the Symposium, we categorised them into five key themes that follow the timeline ‘from bench to bedside’; biomedical research, diagnosis and prognosis, causes of MND, clinical trials and treatments, and improving wellbeing and quality of life. You can read more about each of these themes on our Symposium LIVE webpages. Continue reading

Lessons learnt in the past year…update on clinical trials

Looking for a treatment for MND is the ultimate goal of the whole MND community. Unfortunately, as MND is a very complicated disease, it is not as easy as it may sound. Setting aside the sheer cost of running trials, researchers have to look at all the possible causes of MND (the genes, lifestyle and environment) and then target these with specific compounds and hoping that this strategy won’t be halted by a different biological process. This is made even harder by the large number of possible combinations of these causative factors and the many different ways these can interact.

Thankfully, lots of research groups across the world are doing their best to tackle the adverse disease mechanisms, which is why we heard lots of results of early as well as late stage clinical trials, new strategies to design better treatments in the future, and lessons learnt from previous studies.

While there was much more to hear and read at the Symposium, here we summarise the Clinical trials session (4B), where five presenters reported results and analyses of the treatments they have been investigating. Continue reading

‘There is an app for that’ – the wonders of technology in ALS

At the end of a very busy Day 2 of the Symposium, I sat down with my colleagues for a quick chat. After a while, one of them, who has been with the Association since 1995 told us how someone once asked him: ‘So if you look at the last 20 years, how has the world progressed to know more about MND, since there is still no cure to halt it?’. ‘Technology!’, he replied without hesitation. (Alright, he is a tech guy by occupation, so his opinion might be a bit biased, but he still proves the point I am trying to make).

Technology in the world of research has progressed incredibly far. From the ability to sequence the whole genome of a person in a fraction of the time (and price) that we were able to do a decade ago, to using delicate electrodes and sensors to explore what is happening inside our bodies. Continue reading

Libraries, Doormen and Harry Potter

I usually travel to London two to three times a month for meetings and lab visits. If I’ve got any length of spare time, I head for what I call my ‘London office’ – aka the British Library. It’s close to Euston station, it’s free (!) it has a nice café for informal meetings and it has copies of all the latest textbooks and major research journals.

The way in which a cell turns its genetic instructions into the protein ‘building blocks’ it needs to function and survive is sometimes compared to a library. Continue reading

Understanding disease variability – the 2017 IPG prize winner

Warmest congratulation to Dr Marka van Blitterswijk of the Mayo Clinic in Jacksonville, Florida, winner of this year’s Paulo Gontijo Prize in Medicine.

The Award is presented to an outstanding young investigator working on ALS/MND, with judging based on the significance of a recent scientific paper published by each applicant, plus an evaluation of the relevance and impact of their career to date. I have had the pleasure of serving on the Judging Committee, Chaired by Prof Mamede de Carvahlo, since 2011 and each year the competition gets tougher and tougher. It is so heartening to see the increasing number of excellent young scientists dedicating their careers to the fight. Continue reading

It’s that time of the year again… #alssymp

It was only one week after the 27th International Symposium on ALS/MND in Dublin had ended when we started the next stage of planning for Boston 2017. Now a year has passed and we are here again, waiting to learn about the exciting research that is happening throughout the world. But before we start talking science to you, I thought I would give you a whistle-stop tour of what it takes to organise the Symposium.

It all starts with a selection of a venue at least three years prior the event. This has to tick a number of boxes, including appropriate number and size of rooms for platform and poster presentations, a place for exhibitors, lunch, ease of access both inside the venue as well as outside with respect to the location from transport facilities and so on. A number of site visits are organised to ensure that we are familiar with the venue so that we can plan the location of the platform sessions, locations for exhibitors, lunch, meetings, and networking. And then the year of the event comes… Continue reading