SITraN goes to a festival!

SITraN goes to a festival!

This September, the University of Sheffield successfully hosted its unique ‘Festival of the Mind’ for the third time since 2012.  Forged in collaboration with Sheffield’s creative and cultural communities, the festival comprises a whole host of events that serve to showcase and celebrate the inspiring research taking place within our University.  Over 11 days, visitors came to venues across the city centre to witness a huge range of research topics being brought to life in the form of art installations, captivating lectures, interactive exhibitions, and much more!

Never being ones to pass up an opportunity to engage the public with the exciting research that we do here at SITraN, a group of staff and students from the department decided to get involved!  Armed with our (very fashionable!) brain T-shirts, we headed down to the Moor Market in Sheffield city centre on Saturday 24^th September to deliver lots of fun, neuroscience-themed activities to members of the public.

Over the course of the day, people of all ages visited our stall, where they were able to chat to researchers and discover fascinating facts about the ‘Amazing Brain’.  There were opportunities to look at real-life brains from different animals and learn what makes us as humans more intelligent than mice or birds; people were able to examine slices of brains under the microscope and find out about the important roles of the neurons and other cells that make up our brains; and we got busy with scissors and sellotape, building paper “brain hats” to illustrate the different parts of the brain and the processes that they control in our bodies.

Visitors also had the chance to put their neurons to the test, assessing their reactions and reflexes by trying to catch a falling ruler as quickly as possible, and by trying not to blink whilst wearing lab goggles and having cotton wool balls thrown at their faces (a lot trickier than it sounds!).  Our “mitochondria station” was also a hit: we used electronic circuits to demonstrate how the complex processes that take place in our mitochondria (the tiny, energy-producing powerhouses inside our cells) can become faulty in neurodegenerative diseases like Parkinsons’s disease, and explained how scientists are researching potential treatments for these illnesses by trying to identify and fix these faults.

A fun day was had by all, and it was extremely rewarding and encouraging to see lots of people in Sheffield being inspired by the world of neuroscience research!

Importance of Collaborations

The Importance of Collaborations – A Personal View

This month has seen the publication of two important papers on the genetics of ALS. The first paper describes how variants within three genes (C21orf2, MOBP and SCFD1) which have not previously been linked to ALS have been identified as risk factors for the disease, including in sporadic ALS where there is no family history of disease. The second paper describes how risk variants in NEK1 have been identified in 3% of European and European-American ALS cases. One of the important features of both of these papers is that the results have come about through collaborations, not only nationally, but internationally. Research groups from across the UK, Europe, Turkey, United States and Australia all contributed patient samples to provide the largest cohorts to date for these types of analyses (and these cohorts also included samples collected in Sheffield). This international collaboration is part of an ongoing project “Project MinE” (www.projectmine.com), which aims to sequence the entire genome of 15,000 ALS patients and 7500 controls. The work is being funded by organisations in each of the contributing countries. In the UK, it is the Motor Neurone Disease Association (MNDA) who is raising the funds to sequence patients DNA and this is where some of the Ice Bucket Challenge money raised in 2014 has been spent.

Many other successful collaborations have also involved the researchers in Sheffield, including European collaborations to understand mitochondrial dysfunction in neurodegeneration (MITOTARGET) and to identify novel therapies through a systems biology approach integrating genetic, environmental, and other –omics data (transcriptomics/proteomics/metabolomics) from patients as well as cellular and animal models (EuroMOTOR). These projects were both funded by the EU and one of the unseen benefits was that this brought together a network of researchers with a range of expertise from across Europe. Subsequently, when the EU Joint Programme for Neurodegenerative Research (JPND) called for projects, the network applied successfully for funding to optimise and harmonise of sampling across the consortia partners (SOPHIA) as well as to discover factors that are associated with risk of ALS and specifically those associated with the rate of progression (STRENGTH).

By understanding the disease better, we are in a stronger position to identify therapeutic targets which could improve quality of life, reduce or stop disease progression, and one day perhaps cure ALS. By working together, joining forces, expertise and resources, it is hoped that these results will come sooner.

 Dr Janine Kirby

ZNstress: A new high-throughput drug screening assay for identifying novel motor neuron disease drugs

I work at the University of Sheffield in Dr Tennore Ramesh’s group based at SITraN. We focus on using zebrafish to model motor neuron disease (MND) and have generated models for many different mutations including SOD1, C9orf72 and TDP-43. My particular focus has been on developing drug screening techniques that use these fish to identify new drugs that treat MND.

Zebrafish are a great tool for investigating neurodegenerative diseases and performing drug screening due to their small size, large numbers, transparency, rapid development and their genetic makeup, which is remarkably close to humans. All these pros allow large drugs screens with 1000’s of drugs to be screened rapidly, something not possible before in animal models of MND.

In our most recent paper we report that we have used the sod1 zebrafish model to screen over 2000 drugs, with the ability to screen 100’s each week. Within this 2000 drugs we tested many drugs from past clinical trials in MND and show that like in the human trials they fail to show efficacy in the zebrafish model. The only drug that showed efficacy was Riluzole, the current MND treatment. We believe that this highlights the true power of using the zebrafish as a drug screening model for MND and we are now working hard to analyse the other 2000 drugs, as well as screening further libraries. We are hoping in the very near future we will have some exciting new potential therapies to talk about that may help towards a cure for MND.

Dr Alex McGown

 To read more about my work :full article