Sheffield Institute for
Translational Neuroscience

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SITraN Communications
Laura Evans
E: laura.evans@sheffield.ac.uk
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Latest News

21.07.2015

SITraN Open Day 2015 - Highlights

On Friday 17th July 2015 SITraN opened its doors to the public for an afternoon of talks, tours and demonstrations. The yearly event gives visitors a behind-the-scenes look at the institute’s research into motor neuron disease (MND) and related disorders such as Parkinson’s and Alzheimer’s disease.

Visitors received a warm welcome by SITraN Director Prof Dame Pam Shaw and an update on last year’s highlights. Guest of Honour Sally Light, Chief Executive of the MND Association, presented the charity’s vision and work in partnership with SITraN praising the multidisciplinary, collaborative approach to developing new treatments for MND. Short talks by MND Association/Kenneth Snowman Lecturer Dr Richard Mead, Parkinson’s UK Fellow Dr Heather Mortiboys and Alzheimer’s Society Fellow Dr Claire Garwood followed. The speakers who all received prestigious charity awards for their research presented current strategies for therapy development in MND, Parkinson’s and Alzheimer’s focusing on the role of astrocytes, star-shaped brain cells that support nerve cells, and mitochondria, the cell’s energy generators, which show similar functional defects across neurodegenerative diseases.

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Astrocytes (left), star-shaped brain cells that surround and support nerve cells, and mitochondria (right), the cell’s energy generators, play important roles in neurodegenerative diseases.

During the refreshment break visitors were treated to a selection of cakes and cookies home baked by SITraN staff and students.

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Guests had a chance to chat with the researchers and browse the information stands provided by Parkinson’s UK, the Alzheimer’s Society and the South Yorkshire MND Association. SITraN PhD student Cassy Ashman presented her exhibition “MND: from Loss to Hope”, a joint project created with art therapist Cecilie Browne for the Sheffield Festival of the Mind to generate MND awareness. The research advisory groups for MND (http://smndrag.group.shef.ac.uk)and Dementia were also present with posters and information for anyone interested to join. The groups are hosted by SITraN and members are critically involved in many of the centre’s clinical research projects e.g. the “telehealth in MND” project (TiM), the customisable MND neck collar and the new “myNIV web resource for non-invasive ventilation in MND” (www.mymnd.org.uk).

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A team of SITraN volunteers then took the visitors on a tour to have a look into the laboratories and visit work stations especially set up for the Open Day to discover more about the research taking place at SITraN.  Tours were organised around three themes including “Gene Expression”, “Drug Discovery” and “Clinical Research” ranging from basic science to pre-clinical drug development to clinical trials and assistive technologies for patients. Guests particularly enjoyed getting hands-on extracting DNA from strawberries, using sophisticated microscopes and learning about memory tests as used in the Sheffield memory clinic among many other fascinating demonstrations on offer.

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A big Thank-you to all volunteers and helpers on the day and to all our visitors who made the day a fantastic success.

For more images of our Open Day, please head to our album “SITraN Open Day 2015” on our Facebook page. To see some of the feedback and comments of our visitors on Twitter have a look at #SITraN or follow us @neuroshef.

03.07.2015

Early Career Researcher Awards

SITraN researchers scooped two prizes at the faculty’s Early Career Prize awards as announced by Professor Chris Newman today on behalf of the Faculty of Medicine, Dentistry & Health (MDH) Early Career Researchers Prize scheme judging panel. 

He said: “We had a great number of fantastic nominations from across the Faculty departments for the first year of this new scheme. The judging panel found it extremely difficult to select the winners from those nominated, however I'm thrilled to announce that the following 5 ECRs have been awarded a prize and will receive a grant of £500 for future career development.”

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Winners of the Faculty of MDH ECR Prize Scheme 2015 (pictured from left to right, except Dr Paul Morris)

  • Dr Phil Elks (Infection and Immunity)- Excellence in research
  • Dr Claire Garwood (Neuroscience) - Excellence in enhancing the research environment
  • Dr Heather Mortiboys (Neuroscience) - Excellence in impact 
  • Dr Iwan Evans (Infection and Immunity) - Excellence in research 
  • Dr Paul Morris (Cardiovascular Science) - Excellence in a research and impact 

Prof Newman added: “The judging panel would like to thank all nominated researchers for the excellent contributions they have made to the Faculty.”

29.06.2015

Build-up of DNA damage in nerve cells can lead to dementia

High levels of DNA damage in nerve cells can lead to dementia, researchers from the University of Sheffield have found.

Scientists from the world-leading Sheffield Institute for Translational Neuroscience (SITraN) have discovered a novel pathway contributing to dementia in individuals that lack the typical signs of Alzheimer’s disease in the brain. The research published now in the journal Neuropathology and Applied Neurobiology builds on previous work using brain tissue donated to the Medical Research Council Cognitive Function and Ageing Study (CFAS).

This population-based study shows that one in five of the elderly with documented dementia lack significant amounts of the classical hallmarks of Alzheimer’s disease in the brain, namely ß-amyloid plaques and neurofibrillary tangles. The Sheffield group have subsequently worked to investigate what else may be affecting brain function in this group of people.

The research team led by Steve Wharton, Professor of Neuropathology based at SITraN, focussed on this group of over 65 year olds with little or no classical signs of typical Alzheimer’s or dementia pathology. They isolated nerve cells from donated brain tissue and found that higher levels of DNA damage in nerve cells correlate with cognitive decline as documented in the donors’ medical records.

The scientists further examined the changes in cellular pathways in these dementia cases with high levels of DNA damage compared to healthy control samples. They found changes in genes associated with increased cholesterol biosynthesis, as well as impaired signalling pathways, which are essential for regulating the way that nerve cells respond to their environment, including insulin and Wnt signalling.Steve-Wharton.jpg

“As these changes are independent of established Alzheimer’s disease, they may underlie neuronal dysfunction in these cases and targeting them may provide another potential therapeutic approach to dementia,” said Professor Steve Wharton.

As life expectancy and with it the rate of dementia increases, there is a growing need to identify, prevent and effectively treat dementia. Most studies and clinical trials have focussed on tackling typical Alzheimer’s pathology – ß-amyloid plaques and neurofibrillary tangles in the brain. However, at present dementia remains incurable.

The Sheffield team which leads the neuropathology studies within CFAS has previously demonstrated that there is a significant overlap of what is seen as classical Alzheimer’s pathology between people with and without dementia, particularly in the very oldest.

Professor Wharton added: “Studies of the abnormal proteins deposited in Alzheimer’s, ß-amyloid and tau, are very important for understanding dementia and they are very important as targets for therapies, but it is important, given the very slow pace of development of such treatments, that our focus on the causes of dementia should not be too narrow.

“There is a compelling case to identify other cellular and molecular processes contributing to dementia in order to identify potential new therapeutic targets.”

Carol Brayne, Lead Investigator for the CFA study based at Cambridge University, said: “This work highlights the unique and enormous value of the contribution of individual CFAS participants, as brain tissue donors, and their families to understanding the complexity of dementia across the whole of the older population, compared with findings from groups selected by their contact with particular clinical services."

References:

JE Simpson, PG Ince, T Minett, FE Matthews, PR Heath, PJ Shaw, E Goodall, CJ Garwood, LE Ratcliffe, C Brayne, M Rattray,SB Wharton  (2015)  Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology.  Neuropathology and Applied Neurobiology; published online June 2015 http://onlinelibrary.wiley.com/doi/10.1111/nan.12252/abstract

JE Simpson, PG Ince, FE Matthews, PJ Shaw, PR Heath, C Brayne, C Garwood, A Higginbottom, SB. Wharton. (2015)  A neuronal DNA damage response is detected at the earliest stages of Alzheimer’s neuropathology and correlates with cognitive impairment in the MRC-CFAS ageing brain cohort.  Neuropathology and Applied Neurobiology 41(4):483-96. http://www.ncbi.nlm.nih.gov/pubmed/26095650

26.06.2015

Ambitious research project trials promising new therapy for motor neurone disease

Researchers from the University of Sheffield‘s Institute for Translational Neuroscience are involved in an ambitious European research project aimed at finding a new treatment for motor neurone disease (MND).

The collaboration between world-leading academic research groups aims to identify the therapeutic potential of a molecule (interleukin-2) that occurs naturally in our bodies and helps to regulate our immune system and the inflammation that contributes to motor neurone injury in MND.

Currently, a low dose of the molecule, interleukin-2 (IL-2), is being developed for the treatment of conditions affecting the immune system, including diabetes, arthritis, liver disease, and the complications of treating leukaemia and other cancers with stem cells.

While IL-2 has been used for many years at high dose to treat cancer, it is much safer – but still effective – when used at low doses in these immune disorders, as it can damp down harmful immune responses.

Our main objective is to achieve a breakthrough in the treatment of MND by significantly slowing the progress of the disease through a low dose of IL-2,” said Dr Gilbert Bensimon, University Hospital, Nimes, France, who is project leader of Modifying Immune Response and Outcomes in Amyotrophic Lateral Sclerosis (MIROCALS).

To date, only one drug – riluzole – has been shown to slow the advance of MND, but its impact on the quality of life of people with the illness is marginal. Many other drugs have been tested but have failed.

Professor Nigel Leigh, co-lead and chief investigator for the clinical trial, of Brighton and Sussex Medical School, said:
“We are delighted to be collaborating with world-leading research groups in biomarker development, immunology, genetics and gene expression on this project. This collaboration will allow us to research a number of factors that may affect MND. Taken together, these analyses should allow us to ‘individualise’ responses to treatment that may be revealed during the study.”

In May, MIROCALS was awarded €5.98 million by the European Commission Directorate-General for Research and Innovation, under the EU Horizon 2020 Scheme. Additional support for the Clinical Centres has been awarded by the French Health Ministry Programme de Recherche Clinique (PHRC) in France and is under consideration by the MND Association in the UK.

Other novel features of the MIROCALS study include:

  • the incorporation of ‘biomarkers’ to monitor the activity of the disease, the state of the immune system, and their responses to low-dose IL-2
  • the inclusion of people newly diagnosed with MND. This means that researchers can monitor treatment from an early stage in the evolution of the disease and maximise the potential to detect benefit from low dose IL-2
  • the study of complex genetic factors that may contribute to the response to treatment with riluzole and/or low dose IL-2.

Project planning will start in September this year and researchers intend to recruit the first patients into the trial by September 2016. They aim to complete the study in 2019. In the meantime, the team is working on the essential groundwork for MIROCALS, including a small pilot study in France.

Professor Leigh adds:
“In addition to developing a new treatment for MND, MIROCALS aims to provide a new approach to clinical trials to break the impasse in developing new treatments for progressive disorders that include MND, dementia and Parkinson’s disease."

Professor Pamela Shaw, Director of SITraN and one of the principal investigators involved in this study, said:

This is a very excitinPam pic web size.jpgg experimental medicine study involving several leading European centres for MND research. Not only will we be able to investigate whether interleukin-2 slows the disease course in MND by modifying the inflammatory response within the nervous system, but we will also be investigating in the SITraN laboratories, in a work-package led by Dr Janine Kirby, biomarkers which will tell us at an early stage whether the treatment is beneficial and whether all patients or a particular subgroup develop a positive response.

We were very fortunate to receive funding support for this programme from the EU Horizon 2020 programme and the MND Association in a very stringent grant funding competition.”

25.06.2015

Congratulations to Zahra Zahid: Winner of the Student Employee of the Year Awards 2015

First Year PhD Student Zahra Zahid who works in Professor Annalena Venneri’s Translational Neuropsychology Group has won a University of Sheffield Student Employee of the Year Award in the category “Off Campus Above and Beyond”.  Moreover, Zahra has been chosen to go through to the Student Employer of the Year 2015 national level of the competition.ZZ.jpg

The Student Employee of the Year Awards is a national competition that aims to recognise and promote the outstanding contributions and achievements of students who combine part-time work with their study commitments. Employers are asked to nominate their exceptional students in three different categories; Above and Beyond, Step Up to Leadership and Commercial Impact, these can be either working on or off campus.

Zahra has won the regional award for her work as an A-level Biology Tutor at Oak Tree High School. Zahra said: "I am very grateful to be nominated. Teaching the children, I realised that I have a passion for it. This is something I wouldn’t have found out without taking this part-time job.”

The national award ceremony takes place on Thursday 2nd July in Liverpool – good luck to Zahra and all our University of Sheffield candidates at national level.

To find out more about the Student Employee of the Year Awards visit: http://careersservice.blogspot.co.uk/ and watch the video to hear what this year’s winners had to say https://www.youtube.com/watch?t=102&v=q3OWGVDWCb4

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