Sheffield Institute for
Translational Neuroscience

Contact:

SITraN Communications
Rebecca Brown
E: rebecca.brown@sheffield.ac.uk
T: +44 (0)114 222 2261

Latest News

14.03.2018

New website launch for NIHR Sheffield Biomedical Research Centre

The Sheffield Biomedical Research Centre (BRC) is focused on the pull through of translational neuroscience discoveries in neurodegeneration, neuroinflammation and cerebrovascular disease into clinical studies and experimental medicine trials. This is a cross-faculty University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust collaboration, the first of it's kind in Sheffield and one of 20 NIHR BRCs around the UK. The Sheffield BRC is built in large part on the world-leading work of SITraN and offers new opportunities to progress the work done here along the tranlsational pipeline.  

Read more

09.02.2018

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

12.10.2017

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

07.09.2017

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

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http://opticaljukebox.org/

And take look atComplete Nutrition:

@CNmagazines

https://www.nutrition2me.com/cn-awards

20.07.2017

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

Background

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: https://www.sheffield.ac.uk/news/nr/new-discovery-in-motor-neurone-disease-and-dementia-1.716976

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

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