The Brain: our command centre
By Amy Pullan, Media Relations Officer
Weighing just three pounds, measuring 16cm in length and containing 100 billion neurons, the human brain is unique.
When awake it produces enough electricity to power a small light bulb and information from the brain can move faster than a Formula 1 race car at speeds of over 260 miles per hour.
It is the command centre for our nervous system controlling every movement and decision we make in our lifetime - from our appetite and our heart rate to our emotions and dreams.
The brain is an individual personal storage device securely holding every cherished memory. It influences and shapes our personality, conscience, passion, ambition, motivation and imagination and it continues to develop until our late 40s.
Yet, despite being the most important organ in the body there is still so much scientists simply do not know about the human brain – and more importantly what makes it malfunction.
There are more than 1,000 disorders of the brain and nervous system which, according to the World Health Organisation, affect up to one billion people across the globe.
There are more than 1,000 disorders of the brain and nervous system which, according to the World Health Organisation, affect up to one billion people across the globe.
World-leading scientists from the renowned Sheffield Neuroscience at the University of Sheffield are at the forefront of pioneering research which aims to unlock the mechanisms of our brain in order to understand how it works and how to stop sections of it shutting down.
Sheffield Neuroscience brings together researchers across medicine, science and engineering in order to tackle some of the biggest neurological challenges. From fundamental neuroscience research to novel therapies and pioneering clinical trials, Sheffield scientists are working tirelessly to improve the lives of patients with neurodegenerative disorders.
By combining advanced imaging and innovative neurological tools researchers are able to investigate brain function and dysfunction to further improve the understanding of complex neurological processes in healthy brains and those with a disease.
Ground breaking and interdisciplinary neuroscience conducted at the University of Sheffield, is the key to discovering the secrets of the brain and the mind and helping people in our ageing population to live well for longer.
Although brain research is an extremely intricate and often a painstaking process a chance discovery during a transplant experiment on the ear using cell lines developed by Sheffield researchers could have profound implications for helping restore the function of neurodegenerative disorders such as Alzheimer’s and Motor Neuron Disease (MND).
The delicate operation, which took place in Japan, was the culmination of a long collaboration between biomedical scientist, Professor Matthew Holley, and Neurosurgeon Dr Tetsuji Sekiya at Kyoto University’s Graduate School of Medicine.
“He did all the really hard stuff,” said the modest Professor Holley whose work has been funded by Action on Hearing Loss and the Wellcome Trust.
We had stumbled upon the possibility of a new, non-invasive technique to transplant cells into the nervous system. We showed that the glial scar, rather than an obstacle to regeneration, can actually provide critical cues to the integration of donor cells.
Professor Matthew Holley
"Dr Tetsuji is a brilliant surgeon. He can carefully compress the nerve in the ear, which causes hearing loss similar to that in man, inject replacement cells with great precision and then measure recovery.
"The really hard part is then to section the tissue and to label all the cells we put in. This provides proof that the injected cells reconnect the sensory ‘hearing’ cells to the brain.”
During the first experiments, the two scientists made a startling discovery. The glial scar created by compressing the nerve had previously been regarded as an obstacle to regeneration. When the surgeon injected cells into the nerve – a commonly tested procedure known as intra-neural transplantation – there was no recovery.
“The results were disappointing,” said Dr Sekiya. “Most of the cells died within several weeks and there was no sign of functional recovery, which we measured by recording the brain’s response to sound.”
But then they noticed something unexpected.
Some of the cells that had spilled onto the surface of the glial scar appeared to have migrated into the nerve by themselves and survived.
Professor Holley added: “This chance observation led us to repeat the experiment but to change the delivery by leaving the glial scar intact and placing the cells onto the surface.
“To our surprise they burrowed into the nerve and formed functional connections between the auditory sensory cells in the ear and the cells in the hindbrain.
“We had stumbled upon the possibility of a new, non-invasive technique to transplant cells into the nervous system. We showed that the glial scar, rather than an obstacle to regeneration, can actually provide critical cues to the integration of donor cells.”
The results provide hope for patients who might benefit from nerve cell transplantation.
Incredibly, although the two men have been collaborating for over a decade, they have never met.
As for the future, Professor Holley’s current research is investigating the role of a gene that sets up the conditions for being able to regenerate the tissue.
“We are looking for a drug that you could deploy, so that you don’t have to do gene transfection,” added Professor Holley.
“There are drugs out there that have failed in Alzheimer’s, but they turn out to have an effect on regeneration. So we are trying to find ways of inducing the expression of these developmental genes to recreate the environment for the regeneration of the ear in an adult.”
As the brain is built up of an intricate and complex network – the key to understanding its processes and its malfunction largely lies in revolutionary imaging. At Sheffield, scientists are investigating the cells that help to control signals within the brain to ensure a balance between its energy demand and supply. The findings of this pioneering research could pave the way for new treatments to treat a variety of brain diseases.
Dr Clare Howarth, a Wellcome Trust and Royal Society Sir Henry Dale Fellow, is examining the cells and the signalling pathways involved in regulating the amount of energy brought to the brain by blood in the form of oxygen and the simple sugar, glucose.
“When neurons need more energy, they send a message to the blood vessels. However, the biological mechanisms behind this are not fully understood,” said Dr Howarth, who has recently joined Sheffield’s Neurovascular and Neuroimaging Research Group, international leaders in the fields of neurovascular coupling and preclinical neuroimaging research.
“My research looks at the cells and molecules which control this signalling process. In conditions such as stroke and ageing and in many neurodegenerative diseases such as Alzheimer’s disease, the matching of neural energy demand and energy supply by the blood may be dysfunctional.”
Using state-of-the-art imaging equipment, Dr Howarth is now exploring whether the brain’s blood flow can still meet the energy requirements of the active brain in conditions where the communication between neurons and blood vessels is altered. She said her new project – The role of astrocytes in neurovascular coupling in health and ageing – will determine which signals stimulate increased blood flow to active parts of the brain, and focus on what happens in conditions where this signalling process is disrupted.
Dr Chris Martin, a Royal Society University Research Fellow and member of the research group, is also examining the role that blood plays in brain function. “Over 1.5 pints of blood flow through your brain every minute. Getting this delivered to those areas that need it, when they need it, is a remarkable feat of biological logistics.
“This is a really exciting area of science to work in right now: there is suddenly a much wider recognition that even small disturbances of brain blood flow regulation could have big implications for not only brain health, but also our ability to use brain imaging techniques in humans to understand brain function, and dysfunction.
“It seems likely that what we can currently achieve with these tools is merely the tip of the iceberg.”
Dr Martin added: “There is increasing opportunity for us to connect our work with that going on in other groups.
Over 1.5 pints of blood flow through your brain every minute. Getting this delivered to those areas that need it, when they need it, is a remarkable feat of biological logistics.
DR Chris martin
“For instance, we have recently launched the Neuroimaging in Cardiovascular Disease (NICAD) Network, which links our work to that going on in the Sheffield Institute for Translational Neuroscience (SITraN) and the Department of Infection, Immunity and Cardiovascular Disease. The focus of this network is to investigate how cardiovascular risk factors impact upon brain blood flow regulation using a range of neuroimaging techniques.”
The group has attracted more than £10 million in research funding over recent years – including support from the Medical Research Council, Alzheimer’s Research UK, Wellcome Trust, the British Academy, the Leverhulme Trust, the Royal Society, the Biotechnology and Biological Sciences Research Council (BBSRC) and Engineering and Physical Sciences Research Council (EPSRC).
Dr Jason Berwick, a Reader in Neurophysiology and leader of the Neuroimaging Research Group, is currently investigating how epileptic seizures can start in a small part of the brain before quickly spreading to others. The project is funded by Epilepsy Research UK.
“Finding where seizures begin in the brain and how they spread is important so that patients that aren’t helped by medication can be treated in other ways, for instance using surgery,” said Dr Berwick.
“Using our specialised imaging techniques, we have found that stimulating the whiskers in a rat can make seizures that start in different parts of the brain spread more easily to those areas that receive information from the whiskers.
“This might suggest that areas which are receiving sensory input are more vulnerable to incoming seizure activity. We want to learn how, and measure the changes in the way brain cells work and are fed by blood during the spread of seizures. This knowledge could help to improve treatments that control and prevent seizures.”
Sheffield Neuroscience doesn’t only bring together experts from across the University of Sheffield, but also gives renowned researchers from across the globe the chance to work collaboratively to make a bigger impact and difference to people’s lives.
Looking to the future, the University is striving to create a unique hub and a connected community of genomic researchers, cutting edge data analysts and healthcare professionals across the north of England.
The vision is being driven by former Harvard Professor, Win Hide, who is now Professor of Computational Biology at the Sheffield Institute of Translational Neuroscience (SITraN).
The goal of genomic medicine is to use our understanding of how our genomes affect health and disease to develop much more individualised medical approach, leading to more precise and personal healthcare.
“We have a once in a lifetime opportunity to harness our research capabilities in genomics and data analytics to transform healthcare, not only across the Northern Powerhouse, but the wider world,” said Professor Hide.
“What we are doing is a paradigm shift. We are creating an analytics group of superb quants: scientists who are not working for themselves, but for the university and the city of Sheffield. Their job is to help biomedical researchers, genome scientists and frontline clinicians to interpret the data they are generating and turn it into best practice genomic medicine to save lives and improve healthcare.”
Last month the government announced the creation of a Genomic Medicine Centre (GMC) linking Sheffield and Leeds as part of the 100,000 Genomes project, to transform healthcare and kick-start the UK’s genomics industry.
A future Sheffield hub links to the announcement made by the Chancellor of the Exchequer George Osborne, last year of a £20 million initiative, Connected Health Cities, which will bring the power of data analytics to improve healthcare in the north.
We have a once in a lifetime opportunity to harness our research capabilities in genomics and data analytics to transform healthcare, not only across the Northern Powerhouse, but the wider world.
Professor Win Hide
“The key to success is community,” says Professor Hide, who has helped established world-leading bioinformatics infrastructures in environments as diverse as the University of the Western Cape, in South Africa, and Harvard in the United States.
“Sheffield understands community; it is in its DNA. The future for us is about building linkages between cities and having the infrastructure in place that promotes collaboration. We need to bring industry, investors, clinicians, regional and national policy makers, into a wider data commons built upon a community of collaboration.”
He draws inspiration not just from his experience in South Africa, where he built a national bioinformatics infrastructure from scratch, or from Harvard, where he helped one of the world’s top universities raise its game to catch, and eventually overtake, its rival Johns Hopkins in public health genomics. But it is what happened in Brazil that Professor Hide finds really inspiring. There, a small group of highly motivated people won state funding for a genome project to sequence the bacterial pathogen Xylella.
He added: “Their work not only made the cover of Nature, it also provided a model for how to create a bioinformatics community. They did this by distributing the project through several cities, by collaborating and combining talent and data across a huge state – it has a population of 44 million. We can leverage that paradigm in Sheffield.”
Genomic medicine is an opportunity to turn the scientific discoveries about DNA and how it works into active steps to improve the lives of future patients and identify lifesaving and life improving treatments.
Simon Morritt, chief executive, sheffield children's hospital
His vision is to launch an analytics centre that will “allow for the first time; scientists and clinicians in the city of Sheffield to do world class analysis of their projects and furthermore to propose and secure new levels of high throughput biological analysis that has not been possible before, all within an integrated framework that allows them to find new insights that they had never dreamt they could see before. We do this by hiring the world’s best to work for us – which we are doing now – and in parallel with this we develop a relationship with our customers, the people whose lives we want to impact.”
Simon Morritt, Chair of the recently established Yorkshire and Humber GMC Partnership Board, and Chief Executive of Sheffield Children’s Hospital, said: “Genomic medicine is an opportunity to turn the scientific discoveries about DNA and how it works into active steps to improve the lives of future patients and identify lifesaving and life improving treatments.”
The internationally renowned research conducted at Sheffield Neuroscience focuses on the understanding of the mechanisms of neurodegeneration and the development of new treatments for neurodegenerative diseases.
It is home to the Sheffield Institute for Translational Neuroscience (SITraN), a centre of excellence for basic and clinical research into motor neuron disease (MND) and related neurodegenerative disorders.
SITraN’s goal is to translate scientific discoveries emerging from experimental work in the laboratory into effective therapies and better outcomes for patients in the clinical care setting.
SITraN was unveiled by Her Majesty The Queen in November 2010 with the vision to overcome the devastating effects of degenerative diseases such as MND. The £18 million centre brings together state-of-the-art laboratories and equipment including a clinical database of over 1500 patients.
Over the past six years SITraN has developed into a world-leading facility which is at the forefront of research, expertise and pioneering new treatments from not only MND but other related neurological diseases such as Parkinson’s, Spinal Muscular Atrophy (SMA) and Alzheimer’s disease.
The vision behind the creation of SITraN was to establish a world-class research institute where teams of clinicians and scientists could be brought together under one roof to focus their combined skills on helping to improve the lives of patients affected by neurodegenerative conditions and their families.
Professor Dame pamela Shaw
SITraN is the brainchild of Professor Dame Pamela Shaw, now the Pro-Vice-Chancellor of Medicine, Dentistry and Health at the University of Sheffield.
Professor Shaw said: “The vision behind the creation of SITraN was to establish a world-class research institute where teams of clinicians and scientists could be brought together under one roof to focus their combined skills on helping to improve the lives of patients affected by neurodegenerative conditions and their families.
“Several of our research programmes have already made a difference to life expectancy and the quality of life for people with MND and more exciting and innovative programmes are being developed all the time. SITraN's staff are immensely grateful to all of the supporters, industry partners, organisations and patients who willingly give their time, energy and enthusiasm to help our work.
All of the talented scientists across Sheffield Neuroscience are united under one goal – to unlock the mysteries the brain and its networks to help halt, prevent or reverse neurological conditions which can have debilitating effects on both patients and their family.
By continuing to work together towards a brighter future the researchers in Sheffield are helping to provide real solutions and change lives.
Find out more about SITRAN by watching the video below:
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