The role of the protein TDP-43 in MND due to C9orf72 mutations

Mistakes in the C9orf72 gene are the most common cause of inherited MND, and can be linked to about 40% of all cases. Now that we know that damage to the C9orf72 gene causes MND the next step is to understand how this mutation causes the motor neurones to die. In particular Dr Jakub Scaber is looking at how another cause of MND – the formation of clumps of protein called TDP-43 are linked to changes to C9orf72. (You can read more about TDP-43 in the post about Dr Mitchell’s project yesterday).

Jakub Scaber
Dr Jakub Scaber, University of Oxford

Dr Jakub Scaber is a MND Association/ MRC Lady Edith Wolfson Clinical Research Fellow at the University of Oxford, he is studying how mistakes in the C9orf72 gene and TDP-43 protein cause MND (our grant reference: 945-795).

These fellowships are jointly funded by the Association and the Medical Research Council (MRC). They support clinicians (practising doctors) wishing to pursue scientific research and aim to strengthen the links between laboratory and clinic. Our financial commitment to these fellowships varies between £86,000 and £280,000 for up to five years. For this project the total cost of the grant is £173,697 and the MND Association contributes £86,848 with the MRC paying the rest of the money.Read More »

An insight into TDP-43 – An ENCALS 2015 meeting report

Dr Jakub Scaber, University of Oxford, UK
Dr Jakub Scaber, University of Oxford, UK

Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Clinical Fellow, Dr Jakub Scaber, attended the European Network for a Cure of ALS (ENCALS) meeting from 21-23 May 2015.

Reporting back from the event in Dublin, Dr Scaber summarised the TDP-43 session, including his presentation on recent developments in his own Association-funded research:

The fifth session of the ENCALS meeting focussed on a protein called TDP-43: This is the protein that accumulates in the brains of people living with MND and has been tightly linked to the development of the disease. Abnormal forms of this protein can be found in 98% of cases and this session had some very interesting basic science discoveries around this topic. Read More »

On the sixth day of Christmas MND research gave to me: Blog a Day 2014

“On the sixth day of Christmas MND research gives to you… on the SIXTH month of 2014 we wrote a Blog a Day, and you can still read them all online today.”

Stem cell-derived human motor neurones are being used by researchers to understand more about MND (image courtesy of Dr Scaber, University of Oxford)
Stem cell-derived human motor neurones are being used by researchers to understand more about MND (image courtesy of Dr Scaber, University of Oxford)

The sixth month of the year is June, which is also MND Awareness month. During 2014 we brought you a blog a day (sometimes two) during the month of June,

Ranging from research updates to experiences of getting involved in research, we covered the variety of research funded by the Association and the work of the Research Development team.

Dr Jakub Scaber’s blog post on stem cells was the top-rated blog post of the month, with an impressive image of stem cell-derived motor neurones.

Click here to read all the Blog a Day posts

Posters, posters!

During the 25th International Symposium on ALS/MND there were two dedicated sessions for researchers to view over 300 posters. These posters varied from brain imaging to therapeutic strategies. But what is a poster? In this blog I’ll explain more about the session, as well as highlight some of my personal favourites.

Dr Jakub Scaber next to his poster in Brussels
Dr Jakub Scaber next to his poster in Brussels

A biomedical or clinical poster, is in many ways, like an advertising poster. Researchers use colour and text to present their research in a visual way, to engage and discuss their work.

This year’s poster sessions during the symposium were extremely busy, with large crowds often surrounding just one poster and its presenter! The whole room was a real ‘buzz’ of excitement with poster presenters benefitting from the interest and discussion of their work from researchers around the world.

Our Lady Edith Wolfson Clinical Research Fellow, Dr Jakub Scaber (University of Oxford) said: “I didn’t expect such an interest in my work, I ended up being in discussions for well over half an hour – I didn’t even get chance to remove my coat! I really enjoyed the symposium and got to speak to a few more people than I did last year!” Read More »

Very ‘ice’ research

The ALS #icebucketchallenge, which started in America, has now well and truly hit the UK! The social media craze has seen thousands of people getting involved in raising awareness of ‘ALS’( the most common form of MND), and funds for the Association, by placing a bucket of ice-cold water over their heads. But what happens to the donations?

The #icebucketchallenge has raised awareness of MND and has got people asking ‘what is ALS/MND?’ The donations raised will enable us to support people with MND and fund vital research. We thought we would share with you some of our ‘coolest’ research this bank holiday weekend, which the #icebucketchallenge is helping to fund:

The UK MND DNA bank (link to previous blog) freezers store DNA at a rather chilly -80°C! Now, that’s a lot colder than any #icebucketchallenge (image courtesy of CIGMR Biobank)
The UK MND DNA bank freezers store DNA at a rather chilly -80°C! Now, that’s a lot colder than any #icebucketchallenge (image courtesy of CIGMR Biobank)

Read More »

Human Motor Neurones

Dr Jakub Scaber is a Medical Research Council (MRC)/  MND Association Lady Edith Wolfson Clinical Research Fellow who works in Professor Kevin Talbot’s Laboratory at the Oxford University. Like Prof Chandran’s research, Dr Scaber’s fellowship is also investigating stem-cell derived motor neurones, here he blogs about his research.

jakub mn image

This is an image of motor neurons.

But not just any motor neurons – these are motor neurons that have been derived from skin cells of one of our patients who was a carrier of the most common mutation in the rare inherited form of MND (5-10% of total MND cases) – a mutation in the gene C9orf72.Read More »

Using induced pluripotent stem cells to further our understanding of MND

Dr Jakub Scaber from the University of Oxford is our newest Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Clinical Research Fellow. He is investigating how the newly identified C9orf72 gene causes MND in some individuals using induced pluripotent stem (iPS) cell technology.

Courtesy of Prof Chandran's laboratory, University of Edinburgh
Courtesy of Prof Chandran’s laboratory, University of Edinburgh

Researchers funded by the Association were amongst the first to create human motor neurones from donor skin cells, mimicking the signs of MND. Today, the Association is committed to funding six research projects using iPS cell technology to further our understanding of MND. This includes the recently awarded fellowship to Dr Scaber. Read more about these projects here.

Dr Scaber will be using iPS cell technology to take skin cells from someone living with the rare inherited form of MND (5 – 10% total MND cases) caused by the C9orf72 mutation. Similar to Prof Chandran’s research at the University of Edinburgh, he will then make these cells ‘forget’ what they are and turn them into motor neurones. By studying these cells in detail he aims to find out how this mutation causes MND and whether or not gene therapy can be used as a potential treatment.

Read More »