Friday, 23 September 2016
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
Friday, 2 September 2016
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
Tuesday, 23 August 2016
Soak a Scientist 2016
It is August 2016, and the researchers in SITraN and members of the South Yorkshire branch of the Motor Neurone Disease Association (MNDA) managed to organise the Soak a Scientist event for yet another year! Running under the hashtag #EveryAugustUntilACure, the event attracted plenty of people who didn’t hesitate to donate to support MND research… And to drench some of our finest scientists!
Monika and I before getting drenched
The seat of destiny, ready for the soaking of scientists.
shouting and ringing the bell of destiny to attract some audience and donors
The core of the event, like last year, consisted of scientists getting soaked by members of the public for £1 in Endcliffe Park (but only after the scientist rang the bell of destiny, which I had in my custody). Below are some pictures showing how drenched we got that day, and how much my throat got sore after shouting “soak a scientist for a pound!” all day.
There was also a bake sale which became very popular very fast! All our cakes had been baked by SITraN staff, and ranged from yummy chocolate cookies, to delicious Ferrero Rocher-stuffed cake.
Selection of scientists getting soaked, this includes a child how actually paid to get soaked!!
This year, the event also included a tombola and a treasure hunt for children for the first time. A few children got lots of candy after bringing all the very well hidden answers to questions about SITraN, MND and neuroscience, and adults got lots of nice prizes after getting some tickets for the tombola. We were lucky that a lot of businesses around the park donated plenty of prizes which have now found a new home. We also had two visits from journalists who wanted to document the event! One of them published in The Star, and we were interviewed by Sheffield Live!
Jodie and I, explaining some facts about MND and the event.
We raised a fantastic total of £650. This money will be used to buy new equipment for the lab and material for outreach activities. A great outcome after a day packed with water splashes, cake and a lot of really generous people who wanted to help find a cure for MND.
Alejandro Lorente Pons
Tuesday, 5 July 2016
The latest state of the art imaging equipment bought by you- Thank you from SITraN
This story starts with our research findings taking us down a road of smaller and smaller biology. Therefore to be able to measure the changes in our disease models caused by genetic changes we need ever more powerful microscopes. These do not come cheap and never in our wildest dreams did we truly think that we could purchase the Opera Phenix (Perkin Elmer), a £400, 000 piece of equipment in just over a years’ fundraising. Needless to say this amount was raised by over 19 of our fantastic supporting groups and individuals, without whose support we could not achieve our world class research, both large and small donations are welcomed with the same appreciation and gratitude.
What is so special about this microscope that makes it so expensive I hear you cry. Well, it is a confocal microscope, that is to say it can focus the light hitting our sample into a single plane, this removes all the blur that is obtained in a normal microscope due to the confounding signal from out of focus objects. For some of our research an ordinary microscope is OK, but some of the biological features in our research are so small and so faint that the blur, or noise, obscures what we are trying to study. It is also automated, so it can take over 23,000 images overnight of the cells we are studying. This amount of images would at a best guess take at least about 100 days on a manual confocal microscope. There are other details that make it optimum for our purposes, a patented water immersion optic, a proprietary enhanced light delivery called Synchrony™ Optics (10x more light than normal), multi cameras for speed and sensitivity that add together to mean we get the best picture possible of our model systems to try and understand the causes of disease. Even more exciting for me, as I run the drug screening facility here in SITraN, it means we can run drug screens to try and find compounds (possible drugs) that can remove or reduce the number of RNA foci (a pathological hallmark) found in the most common genetic cause of motor neuron disease (MND also known as ALS). We can also increase the throughput of screening of our in vivo fish models, locating and counting specific neurons within the brain of zebrafish. This machine will benefit all our research groups including those studying Parkinson’s Disease, Alzheimers, spinal muscular atrophy (SMA) and Stroke.
Our next challenge is handle the data from all the experiments we want to run, as an overnight experiment could generate as much as half a terabyte of data! That is probably more data than you have stored on your TV at home about 60 hours (HD).
Dr. Adrian Higginbottom- Senior Scientific Officer, Manager Drug Screening Facility.
Monday, 13 June 2016
Why Bioinformatics, Biostatistics and Computational Biology are crucial for Neuroscience?
Neuroscience is an interdisciplinary science that is strictly engaged with other disciplines ranging from cognitive science and linguistics to medicine and genetics.
The ever-growing volume, complexity and potential of neuroscience data is challenging for the current analytical techniques. It becomes increasingly important to be able to retrieve information from this these data into new knowledge. Bioinformatics, Biostatistcs and Computational Biology hand to Neuroscience a new generation of statistical and computational methods, to give actionable insight to data and foster discoveries involving large-scale data. The Sheffield Institute for Translational Neuroscience (SITraN), within the Faculty of Medicine, Dentistry & Health, is a multidisciplinary research center focused on neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS also known as motor neurone disease MND), Parkinson’s disease and Alzheimer’s disease. Researchers at the Institute work closely with patients affected by neurodegenerative diseases and use human bio-samples in their research. Moreover SITraN has recently acquired an Illumina HiSeq machine generating RNA-seq data. This highlights the importance of Bioinformatics, Biostatistcs and Computational Biology at SITraN.
Professor Neil Lawrence and Professor Winston Hide are world leading scientists in data driven and dynamic modeling for biotechnological applications. Their researchers’ groups at SITraN represent the opportunity for a coordinated approach to the development of new computational methods to find therapies based on rational targets of proven preclinical effectiveness.
In this light Bioinformatics Awareness Days (BAD days) are held at SITraN to help scientists in handling and analyzing high dimensional biological data.
The Bioinformatics Awareness Days would be days devoted to Bioinformatics. As a Marie S. Curie postdoctoral fellow @ SITRaN, I am glad to organize such an event to give my practical contribution in Bioinformatics. The sessions will be self-contained and should last at most 2 hours.
The first day focus was on "R&Bioconductor and Multiple hypothesis testing" and was held on Wednesday, 4 May 2016 at SITraN.
We had massive attendance and good feedback.
Next events to come!
Wednesday, 27 April 2016
Real brains and crafty handprint neurons for British Science Week
In mid-March British Science Week took off with more chaos and craziness than ever before with SITraN staff taking part in public talks, Discovery Night and school visits.
The SITraN team visited two local schools where the children patiently sat and listened to a talk about how the brain and spinal cord function to keep us living, moving and thinking. Following this the children visited 6 different workstations: the human brain, investigating the brain, senses, handprint neurons, real brains, and motor skills.
At ‘the human brain’ workstation children spent time discussing brain regions and creating brain hats, which are always a big hit.
The iconic microscope was used for ‘investigating the brain’ and children looked at real brain slices under the microscope. However, it appears that many of the children were more interested in how the microscope worked than the brain tissue underneath it!
The children explored their senses using puzzles at the ‘senses’ workstation by smelling the contents of jars, doing jigsaws blindfolded, guessing the contents of boxes based on touch and exploring vision with optical illusions and braille.
Plenty of glitter was spread about at the ‘handprint neurons’ workstation, where children used their handprints, pom-poms and pipe cleaners to design and decorate a neuron to take home.
The ‘real brains’ workstation produced plenty of exclamations of “eeew!” as the children looked at real animal brains and discussed their levels of intelligence alongside MRI images of the brains. At one point, whilst holding up a bird brain, a researcher asked, “whose brain do you think this is? It has wings…” to which a child replied “the tooth fairy?”
Finally, the ‘motor skills’ workstation explored reaction skills and reflexes with games such as catching the ruler before it falls and trying not to blink when cotton wool is thrown at your eyes whilst wearing safety goggles.
It was great to see the children skipping out of school wearing brain hats, waving neurons and exploring their newfound knowledge of the brain! All-in-all much fun was had and lovely feedback was received from the schools for the second year running.
There’s plenty more outreach before the next British Science Week including an outreach afternoon in SITraN on Saturday 23rd April!
The SITraN team.