Sheffield Institute for
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Two Day Hackathon To Improve Medicine & Healthcare - March 2018

There are many problems that plague medicine and healthcare. It is a wonder why these problems still exist, given how crucial health is to everyone here on Earth.

What better way to accelerate the solving of these problems by integrating technology into our radical solutions, while providing a safe, creative environment for people to do so?

HackMed aims to bring together hackers, dreamers, and doers to solve problems related to humanity’s elementary need, health.

HackMed is a medical hackathon aimed at developing creative solutions to solve problems within medicine and healthcare. It is a student-run event for individuals from various backgrounds interested in the crossroads of life sciences and technology.

Throughout the weekend, hackers at HackMed will have a unique opportunity to learn from each other, build awesome projects together, and share them with other hackers. This will allow a multi-disciplinary mesh of people working on developing solutions to pressing problems within healthcare and medicine.

For further information and to apply to join, please click here


SITraN High Content Screening Picture Competition 2017 Winner Announced

  • The competition ran from Monday 16th October until 30th October
  • Tweeters voted for their favourite image generated by the PerkinElmer Opera Phenix High-Content screening system by liking a tweet of the picture
  • Mohammed Karami has been announced winner and received a cheque of £500 from Perkin Elmer for High-Content-Imaging work from SITraN to be presented at an industry conference
  • See the shortlisted entries, runners up and terms and conditions below

Read more


Video information website myTube, by patients for patients is named 'Nutrition Resource of 2017' by top public health & primary care nutrition publication

Pioneering patient-led information website myTube is announced winner of the Nutrition Resource of the Year award by Complete Nutrition Magazine - The UK’s No.1 clinical, medical & health nutrition publication

Patients and carers shared their insights into difficult care decisions they have faced in living with Motor Neuron Disease and made a pragmatic, honest and personal video resource website to inform others thinking about  tube feeding in case of compromised eating and swallowing. The patients and carers took the research done at SITraN by Prof Chris McDermott’s team and made it real and relevant to everyday life for those affected by MND. 

The myTube team included patients and carers and past members of the South Yorkshire MND Association and members of the Sheffield MND Research Advisory Group of patients and the public, SITraN researchers, and Registered Nurse filmmaker and videographer Cathy Soreny to record patient stories about having a Percutaneous endoscopic gastrostomy (PEG) tube fitted.  From thinking about it, deciding to have it, deciding not to have it, and the practical reality of living with and caring for someone with a gastrotomy feeding tube, a wealth of lived experience is conveyed in the collection of short videos on the user-friendly website (web design by Ammba Digital).

The myTube team had this to say:

“The whole MyTube Team are very pleased to accept this Award from Complete Nutrition. It is great recognition of not only the final resource, but also the methods used during its development. The current evidence about decision making prior to having a gastrostomy feeding tube placed was interpreted and presented under the expert guidance of our patients living with Motor Neurone Disease (MND) and their families. The collaborative process followed, allowed the relevant clinical information to be translated through the words of the patient themselves in a series of short films. We are so pleased that the health professionals who have voted for MyTube recognise the value of this resource, and we hope that they will continue to recommend it to patients living with MND who are making the decision about gastrostomy tube placement.”

The myTube website is great example of what can be achieved to benefit patient's and carer's lives through their involvement in research, providing a great, independent online resource for those facing a similar challenge. 

The myTube project was co-funded by the MND Association and Westfield Health Charitable Trust.

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To share this story on social media:

And take a look at more health research documentaries, including a dietitian living with a nasal feeding tube for a week


And take look atComplete Nutrition:



C9orf72 repeat expansion drives neurodegeneration by inducing DNA damage and compromising DNA repair

  • Study published in Nature Neuroscience this week
  • Important C9ORF72 pathophysiology revealed
  • Could pave the way to new treatments for Dementia and Motor Neurone Disease

C9ORF72 hexanucleotide repeat expansions are a major cause of Frontotemporal Dementia and underlie 10% of all Motor Neuron Disease cases. Important pathophysiology delineating the toxic effect of the repeat expansion was published in Nature Neuroscience this week.  This paper is the result of a cross-faculty effort between SITraN and the Department of Molecular Biology and Biotechnology, jointly supervised by Professors Mimoun Azzouz and Sherif-El-Khamisy

Video animation credit: Nora El-Khamisy


The C9orf72 gene contains an intronic repeating region of guanine and cytosine nucleotides that is expanded in C9orf72 linked FTD and MND. GC-RNA repeats are prone to hybridize with the DNA template strand during transcription producing a stable 3-stranded nucleic acid structure called an R-loop that predisposes DNA breakage.

Enzymatic DNA repair is part of routine maintenance for cells when structural damage like single or double stranded breaks occur. Double stranded breaks (DSBs) can lead to dangerous genome rearrangements and trigger apoptosis at high levels. In post-mitotic cells like neurons, low levels of unrepaired DNA damage can accumulate over-time aging the cell. A master kinase called ATM responds to DSBs as part of the DNA repair response.

The Findings

Immunohistochemistry on post-mortem tissues from patients with C9ORF72-MND confirmed an increased presence of R-loops and possible marks of an impaired ATM repair system. To model these findings in vitro, the authors used AAV viral vectors to deliver the toxic products of the C9ORF72 gene to cells. Increased R-loops and DSBs were subsequently observed. The master kinase ATM was not activated in response to the DSBs and was below activation levels found in control cells. This led to the hypothesis that the C9ORF72 repeat expansion impaired ATM-mediated DNA repair.

To test the hypothesis in vivo, mice were transfected with normal and repeat expansion versions of C9ORF72 products. Mice with the repeat expansions developed an MND phenotype and the hallmarks of R-loops, DSBs and an impaired ATM response. The next question was, what is it about the repeat expansion that causes the ATM response to be impaired?

Autophagy; the garbage disposal system of the cell, whereby defective or otherwise unwanted proteins and other constituents are recycled into their reusable parts, was found to be initiated by the normal function of the C9ORF72 gene by Kurt de Vos’ team published in EMBOJ last year.  A protein called p62 accumulates in cells with a defective autophagy system and p62 aggregates are a characteristic feature of C9ORF72 pathology. Furthermore, deficient autophagy was reported to impair DNA repair leading to genome instability elsewhere in the literature. A p62 complex directly binds to components of the DNA repair response preventing DNA repair proteins from being recruited to the site of DSBs. In the current paper, a gene therapy technique using a complementary RNA sequence to silence p62 mRNA transcripts depleted the level of p62, restored the ATM repair process and reduced the level of DSBs in cells transfected with C9ORF72 repeat expansion products.

Elucidating the cell pathways that cause motor neurons to die in MND and FTD paves the way for new therapies to be developed to tackle these targets.

Find out more:

Read the full paper:C9orf72 expansion disrupts ATM-mediated chromosomal break repair

University of Sheffield press release:

This work was funded by the European Research Council and Wellcome Trust. 




New Target to fight Motor Neurone Disease using gene therapy uncovered by Neuroscientists at the University of Sheffield

  • New mechanism discovered in the most common genetic cause of MND opens up a novel field for potential therapeutic intervention
  • Alleviating Motor Neurone Disease (MND) is central to the research carried out at the Sheffield Institute for Translational Neuroscience (SITraN)
  • In work funded by the MND Association, a breakthrough has been achieved in collaboration with the MRC Mitochondrial Biology unit of Cambridge the Nationwide Childrens Research Institute in Ohio and the UCL Institute of Neurology in London.

Every day six people in the UK die from Motor Neurone Disease, which causes progressive paralysis as the nerves supplying muscles degenerate for reasons that are incompletely understood. At any one time nearly half a million people worldwide suffer with this devastating condition but in the majority of cases it is not known what causes the nerves supplying muscles (the motor neurons) to die. The commonest known cause is a mutation in a gene called C9ORF72. About 1 in 10 cases of MND is linked to having an expanded repeating region of DNA in a part of the C9ORF72 gene that is not usually made into protein.

Delving into the molecular core of how the products of this gene behave in the cell, in work published today in Nature Communications, scientists at SITraN have discovered a key pathway in C9ORF72-linked MND. Tests in patients’ cells and in fruitfly models of MND indicate that targeting this pathway is a novel angle to tackle the degeneration of nerve cells (neurodegeneration) that occurs in MND.

Lead author Dr Guillaume Hautbergue has studied the molecular biology of RNA for over 25 years and spent 10 years from 2002 – 2012 in the department of Molecular Biology and Biotechnology at the University of Sheffield in Professor Stuart Wilson’s laboratory developing methods to study the mechanisms that export messenger RNA from the nucleus to the cell cytoplasm. There, Dr Hautbergue established the accepted model of how this works in humans before taking up a lectureship in Translational Neuroscience at SITraN. Translating advances in fundamental discovery science into real benefits for patients is the raison d’etre for SITraN so it is very satisfying that harnessing Dr Hautbergue’s developments in the field of RNA biology has now led to the discovery of a new therapeutic strategy of neuroprotection in MND and potentially other neurodegenerative diseases. 

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From left to right: Dr’s Guillaume Hautbergue, Lydia Castelli and Laura Ferraiuolo  contributed equally to this work that was jointly supervised by Dr Guillaume Hautbergue, Dr Alexander Whitworth from the MRC Mitochondrial Biology Unit at the University of Cambridge and Prof Dame Pamela Shaw from the Sheffield Institute for Translational Neuroscience (below). 


The corresponding authors of the study are Dr Guillaume Hautbergue ( and Dr Alex Whitworth ( 

While the main purpose of DNA is to code for proteins to be built in the cell, we know that a lot of DNA doesn’t code for protein after all, such as the repeating region of the C9ORF72 gene. In healthy versions of the gene the repeated region (usually under 30 repeated units) is simply cut out of the RNA copy of the gene before the RNA is exported from the nucleus.

In C9ORF72-MND however, the repeated region is much larger – even up to a thousand repeated units and leads to a build up of the RNA repeats inside the nucleus but also, unexpectedly is made into abnormal toxic constituents in the cell cytoplasm called dipeptide repeat proteins. The discovery of dipeptide repeat proteins was puzzling to scientists as this type of non-protein coding RNA does not normally exit the nucleus to get to where protein can be made.

Dr Hautbergue and colleagues, who have developed expertise in the mechanisms of RNA nuclear export, looked to see how the pathological repeating precursor RNA molecules, that should be confined to the nucleus, might be getting exported to the cell cytoplasm where the toxic protein is made. It turned out that just one component of the nuclear-cytoplasm transport system, a protein called SRSF1, was responsible for shuttling the RNA repeats out the door of the nucleus into the cytoplasm. Crucially, the breakthrough in this discovery is that SRSF1 is only needed to help the pathological C9ORF72 RNA to exit the nucleus. All other, useful protein coding RNAs can get to the cytoplasm without it. Partially removing SRSF1 from the cell in fruitfly models and cultures of cells from MND patients using gene therapy (see the Spotlight on Technology box in yellow for more on the techniques used in this work) had no adverse effects  in the models tested and prevented the toxic dipeptide repeats from being formed. This is the first time that the nuclear export of pathological repeating RNAs has been elucidated in a neurodegenerative disease and the first time that it is shown that targeting this pathway provides a promising therapeutic strategy of neuroprotection.

Interestingly a number of other genes that cause neurodegenerative diseases including Huntington’s disease, Fragile-X associated Tremor/Ataxia Syndrome, Myotonic Dystrophy and other disorders affecting muscle co-ordination contain similar repeat expansions as those found in the C9ORF72-MND gene. So looking at whether those expansions are turned into toxic proteins and whether this can be prevented through turning off a specific nuclear exporter too, might open up a whole new area of research into treating neurodegenerative disorders. A patent application was filed for the use of SRSF1 antagonists in the treatment of neurological disorders. 

RNA Explained


The fundamental pathway in biology is that information flows from the DNA code; a genetic ‘blueprint’ for proteins – the building blocks of life, to microscopic cellular machinery that produce proteins to order from a pool of amino acids in the cytoplasm of the cell. The DNA supplying the recipe of instructions to make a particular protein is too large to get from where it is housed in the nucleus of the cell out to where the protein producing machines are located outside the nucleus, so the message is sent via a messenger molecule called RNA. RNA takes a copy of the blueprint coded instructions from the DNA out of the nucleus to where proteins can be produced in a process called ‘translation’. Regions of DNA that are not translated into protein are still copied into RNA but then usually cut out of the final RNA molecule that is exported out of the nucleus.

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Spotlight on Technology

Two cutting-edge techniques were deployed in the work that led to this breakthrough. First, to look at the disease mechanisms inside individual patient’s neurons (nerve cells) a specially devised method developed in Ohio by Dr Laura Ferraiuolo was used to reprogram skin cells taken from a small skin biopsy into neurons, the specialised cells of the nervous system that cannot be easily accessed to study in life. Animal models of disease are extremely useful to scientists to test new theories and treatments but have the limitation of being simplified versions of disease made from a uniform model whereas a genetic disease like MND can present more variably in humans that are genetically more diverse from one another. This is thought to be one reason why new therapies that give promising results in animal models have failed to perform as well in patients on clinical trials. The fruitflies used in this research all had an identical 36 number of the pathological C9ORF72 repeated units inserted into their DNA. In patients with C9ORF72-MND however, the number of repeats can vary very widely from just over 30 to over 1000 units. It could have been the case that SFSR1 only transported low number repeat expansion pre-RNA out of the nucleus. Testing out the strategy in cells actually derived from patients powerfully indicates that the approach will be relevant in the real disease.

The gene therapy approach used in the research took a therapeutically engineered virus to get an RNA molecule inside the cell that would interfere with RNA for the production of SFSR1. Interfering RNA prevents the targeted protein from being produced. Effectively knocking-down the amount SFSR1 in the cell stopped the toxic C9ORF72 dipeptide repeat protein from being formed and rescued the cell from neurodegeneration. Gene therapy using viruses is extremely effective as the virus can stay inside the cell and continuously produce the therapeutic interfering RNA over a long period of time for the ongoing treatment of a genetic disease. Dr Hautbergue and colleagues Prof Mimoun Azzouz and Prof Pamela Shaw at SITraN are currently in talks with companies such as AveXis Inc. and Pfizer to take forward a translational gene therapy program and a new PhD student starting in September will be trying out the strategy in a mouse model of C9ORF72-linked MND. 

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