Investigating C9orf72 and TDP-43 proteins in a fruitfly model of MND

Background to C9orf72 toxicity

We know that damage to C9orf72 (both the gene and the protein it makes) is a crucial step in why some people get MND and why some people get frontotemporal dementia. There are three possible reasons why C9orf72 is toxic. 1) the way the gene is damaged alters how it normally works. 2) the formation of clumps of RNA – a by-product of the damage and not normally seen in cells, and 3) the formation of very short, new and unwanted proteins called ‘dipeptide repeats’ or ‘DPRs’, again these are not normally seen..

There’s evidence of all three types of toxicity within the motor neurone, but we don’t know how they work together or if one is more toxic than another. We also know that the protein TDP-43 forms clumps in motor neurones affected by the C9orf72 gene.Read More »

Developing models to test new treatments for MND

Developing disease models is important for furthering our understanding of MND and allows researchers to screen potential new drugs for a beneficial effect. Moving a promising ‘nearly drug’ from the lab to being tested in people is known as ‘translational research’.

Dr Richard Mead
Dr Richard Mead

Dr Richard Mead was awarded the Kenneth Snowman/MND Association Lectureship in Translational Neuroscience in May 2014. The Lectureship is part funded by the MND Association (our reference 983-797).

We have recently received a progress report from Dr Mead. Its clear that his background and experience in this area – including several years working in the pharmaceutical industry – has helped him to rapidly develop a portfolio of projects and collaborations with academic and industry partners.Read More »

Preventing TDP-43 deposits in motor neurones

Deposits of the protein TDP-43 are found within the motor neurones in the majority of cases of MND, and are considered a pathological hallmark of the disease. While we do not fully understand how these deposits are formed, previous research has shown that activation of a process called the Unfolded Protein Response (UPR) can cause TDP-43 protein to deposit in the motor neurones.Read More »

Toxic proteins may cause motor neurones to die in C9orf72 MND

MND Association and Alzheimer’s Research UK-funded researchers from University College London have identified that toxic proteins may cause motor neurones to die in C9orf72 MND and frontotemporal dementia. Published open access in the journal Science on Thursday 7 August, this research explains more about one of the most common forms of inherited MND.

The brain of a transgenic fruit fly Drosophila melanogaster, used to study neurodegenerative diseases, with cell nuclei (stained purple) and glial cells (green). Image courtesy of Teresa Niccoli, UCL Institute of Ageing, London, UK.

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The MND Researchers Bake off Champion!

As well as helping out with our ‘blog a day’ during MND Awareness Month, we also asked our researchers to get involved in ‘baking’ to become our first ‘MND Researchers Bake off Champion’. We received some great science-themed cakes, from zebrafish biscuits to a Nuclear Magnetic Resonance(NMR) machine cake!

Our Director of Research, Dr Brain Dickie said: “It was really tough to judge, they were all great entries! (might need to taste next year though…!). Of the seven entrants there was one that I think wins by a short head, scoring on appearance, originality and relevance to MND research, with an extra mark for sheer wackiness – the ribosome translating a C9orf72 repeat expansion cake!”

The winning cake was by Jenn Dodd, a PhD student at the Sheffield Institute for Translational Neuroscience (SITraN)! Here Jenn describes her cake and how it feels to be the MND Researchers Bake off Champion!

Jenn Dodd's winning ribosome translating C9orf72 cake!
Jenn Dodd’s winning ribosome translating C9orf72 cake!

The winner’s speech:

I decided to bake the cake, as at SITraN we have a weekly cake club and it was my turn to bake in June. I thought entering the competition would be a good way to get involved in MND awareness month and thought it would make cake club a bit different!

Small structural units called cells make up the human body. They convert food and oxygen into energy to produce chemically reactive machines and building blocks called proteins. There are thousands of different proteins made and so special templates called RNA are sent to a protein-making factory in cells called the ribosome. The ribosome makes proteins from the RNA templates in a process called translation (Read more about how cells make proteins here).

The cake shows a ribosome (yellow) translating RNA (the stripey sweets) to make a protein (the flying saucer chains). The protein that is being made is C9ORF72, a protein with an unknown function that is involved in some cases of MND.

I’d like to say thank you and I am really please to have won the bake off with my cake experiment!

X-rays for MND research

Dr Gareth Wright, based at the University of Liverpool, is a postdoctoral researcher funded by the MND Association. His research is all about using physics and x-rays to further our understanding of MND. Here he gives us a taste of why X-rays  are important.

The background to X-rays

We have a long history of X-ray science in Liverpool. In 1896 Sir Oliver Lodge used X-rays to image a lead pellet embedded in the hand of a 12 year old boy. This was one of the first medical uses of X-rays and allowed the bullet to be successfully removed. Charles Barkla made an observation in 1904 considered to be the birth of X-ray science; X-rays behave like visible light and are part of the electromagnetic spectrum. They have wavelength around 0.1 nm (0.000000001 metres!) which makes them perfect to resolve individual atoms in a molecule (eg water).

Gareth Wright- soleil
The synchrotron in Soleil, France

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Baking with proteins, mRNA and DNA

Today marks the start of MND Awareness month 2014 and our MND Research ‘blog a day’. Before we post our first guest blog we thought we’d set the scene by reminding you about genes and proteins.

As our fundraising campaign ‘Bake it!’ is back for 2014, we thought we’d re-blog our ‘baking with proteins, mRNA and DNA’ in order to help bake MND history!

Thank you for reading our ‘blog a day’ this Awareness Month. We would gratefully appreciate your thoughts and feedback via this short 2 minute survey.

MND Research Blog

Each and every one of us is made up of thousands of different ingredients, which all combine together to create something amazing; life. Perhaps the most important of these are proteins.

Each protein in the body has its own special job to do. From making our muscles contract to controlling blood sugar, proteins are an essential ingredient in life.

In MND research we have identified a number of MND causing genes. These are genes that are found to be mutated in some people living with MND, which somehow causes the motor neurones to die. But, how does this happen? How does a gene form a protein? This blog post explains how an MND causing gene becomes a protein.

As simple as baking a cake

Here at the MND Association we love our cake. So, I thought what better way is there to describe how we make proteins?

cheesecake cheesecake

Every cell…

View original post 631 more words

A PERK for neurodegenerative disease?

Our bodies need to be able to make new proteins, to maintain long term memory. So if the ability to make new proteins is switched off, does this cause Alzheimer’s Disease? New research findings published yesterday by scientists based in Leicester take us closer to answering this question. Journalist are describing this as a step forward for all neurodegenerative disease, so I wanted to explain what the researchers found, and what it might mean for MND.

What’s the story?

The activated form of a chemical called ‘eIF2’, is found in higher levels than normal in the brains of Alzheimer’s Disease patients. (In it’s turn, eIF2 is activated by an enzyme called PERK – hence the name of the blog post.. !).

Last month (September 2013) researchers found that genetically blocking the activation eIF2 prevented memory problems in a mouse model of Alzheimer’s Disease. The research published yesterday showed that in a mouse model of prion disease, chemically blocking eIF2 (as opposed to genetically blocking it) helped prevent the development of prion disease (Variant CJD or ‘mad cow disease’ is an example of a prion disease).

The chemical block was given to mice orally (one of way of doing this is to give it to them in their food). It got to the brain OK and effectively blocked eIF2, but the chemical did have serious side effects. So it’s a possible turning point for drug treatment for Alzheimer’s Disease and prion disease, but not the answer.

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