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Genome-editing research: not just a question for scientists

2 Sep, 2015
Credit: Matthew Chattle. Wellcome Images. CC-BY-NC-ND

Credit: Matthew Chattle. Wellcome Images. CC-BY-NC-ND

The Wellcome Trust is proud to support the development of cutting-edge science, but we are also aware of the importance ensuring that new technologies are used responsibly. The CRISPR-Cas9 genome-editing process and its applications in research are an area of growing interest. Ahead of a range of international meetings and consultations, the Trust is today outlining its initial position on the technique. Katherine Littler, Senior Policy Advisor at the Wellcome Trust explains…

The CRISPR-Cas9 technique for genome editing has been in use by researchers for around three years, and as awareness of the technique has grown, potential new applications are being considered.

The technique exploits a naturally occurring phenomenon, to allow sections of an organism’s DNA to be accurately and efficiently targeted, then removed or replaced using “molecular scissors”. Researchers are now using the technique to help them better understand the function of different genes, and the effect they have on health and disease.

The ability to edit genes for research is not new, and there are various techniques already in use, but with the potential for CRISPR-Cas9 to make the process more efficient, many people are thinking about how it could be used therapeutically. One use that has attracted particular attention is the possibility that it could one day be used clinically in human embryos, to prevent serious inherited conditions.

In reality, this is a long way off, we are still in the early stages of understanding the full potential of CRISPR-Cas9 and more research needs to be done.

While there has been some good progress developing potential somatic (non-reproductive) cell therapies using this technique, it will be years before we know enough to apply it safely in reproductive cells.

B0002684 DNA jigsaw - gene therapy Credit: Adrian Cousins. Wellcome Images images@wellcome.ac.uk http://wellcomeimages.org DNA jigsaw - replacement of a faulty gene by gene therapy Digital artwork/Computer graphic 2002 Published: - Copyrighted work available under Creative Commons by-nc-nd 4.0, see http://wellcomeimages.org/indexplus/page/Prices.html

Credit: Adrian Cousins. Wellcome Images. CC-BY-NC-ND

But, at the Wellcome Trust we believe it is important that discussions about the application of new scientific techniques start early, and are not limited to the community of scientific researchers who are currently using them. We want to encourage wider engagement with the questions that new techniques may raise, and we feel that it is important to do this as early as possible.

We also believe that the discussions about the potential applications of genome editing should not stand in the way of basic research that makes use of the technology to inform our understanding of human biology, health and disease.

Today we are publishing our initial position statement on genome editing. In short we would like to make it clear that we support the development of new techniques and applications of science that could help improve human and animal health, but we want to do this in the context of wider discussions that should be had about how and where the technique should, and shouldn’t, be used.

Biomedical and social science researchers, ethicists, healthcare professionals, funders, regulators, patients and families and the public should all have a voice in this discussion.

The joint position statement that we have released today, (also signed by AMRC, AMS, BBSRC, and MRC) is an initial statement to show that we want to be engaged in, and help to facilitate discussions on this topic. We fully expect this to evolve and be refined as the conversation (and the research) moves forward.

We know that CRISPR-Cas9 is already an effective tool in basic research, and in future could be used to treat disease, but we are not there yet – not scientifically, ethically or legally. As the technology evolves, we should maintain the robust regulatory framework that has already allowed the UK to become a respected global leader in the application of science in an ethical manner

We want to proactively engage with the wider questions raised by genome editing, and feel that the best way forward at this point is to encourage open discussion that includes scientists, ethicists and the public. We look forward to being part of that discussion and would welcome your thoughts.

You can read the full Wellcome Trust position statement on genome editing on the genome editing spotlight pages on our website.

Image of the Week: Medical detection dogs

28 Aug, 2015
Casper the poodle helps his owner keep track of her blood sugar levels

Casper the poodle helps his owner keep track of her blood sugar levels

At Trust HQ we’re used to welcoming researchers, grantholders, artists and all manner of interesting people into the building, but this week things were a bit different…

To mark National Dog Day in the UK, we had some furry friends join us, and they brought their owners along to tell us more about the way dogs can help with human health.

You’re probably familiar with the concept of guide dogs, who are specially trained to help blind and partially sighted people during everyday life, but what about medical detection dogs?

These dogs work with individuals who have a range of diseases including type 1 diabetes, Addison’s disease, and narcolepsy. Using their incredibly attuned noses, these dogs are able to ‘sniff out’ minute indicators of changes in the body that could signal the onset of a dangerous medical event. A dog’s sense of smell can be anywhere from 10,000 to 100,000 times more sensitive than ours, with the part of their brain dedicated to processing smells also being proportionally much larger.

For diabetics whose blood sugar levels change rapidly for example, the dogs are able to detect changes in blood sugar and alert their owners if the level falls below, or rises above, the normal range. They are also able to fetch help or medical supplies if needed.

The dogs can also be placed with people with severe, life threatening allergies – a  trained dog can detect an approaching person who had been eating nuts as far back as two days ago!

The charity Medical Detection Dogs has placed around 60 dogs with people who are unable to sense the onset of an impending life-threatening medical emergency, and they’ve got even bigger ambitions for the future. They are looking at whether it is possible to use dogs to detect indicators of cancer in a person’s urine, which could speed up early diagnosis. On-going research suggests that when presented with samples of urine, dogs are able to accurately identify certain types of cancer through the odour.

“Our work will eventually help scientists create an ‘electronic nose’ that could screen urine samples” says Christina Bowden from Medical Detection, and though she says that dogs will never replace doctors, she does hope that in future clinicians may send urine samples to be screened by the dogs.

To find out more about Medical Detection Dogs please visit their website

Related: Read more about dogs detecting cancer in the Mosaic Extra ‘Sniffing out ovarian cancer

Image credit: Colin Walker

Life as a Wellcome Trust Intern

25 Aug, 2015

Wellcome Trust Summer Internship

The Wellcome Trust offers a number of paid summer internships at Trust HQ. These are aimed at giving current undergraduates the chance to experience working an area of the Trust that interests them, and we hope to inspire, support and develop the next generation of people who can make a difference. As their time at the Trust comes to an end, we caught up with them to find out what have been their highlights, surprises and what they will take away with them as they return to University…

Internship Highlights

"The Reading Room is the first aspect of the Wellcome Trust, or the Wellcome Library specifically, that drew me towards the internship opportunity here. I loved the idea of working for an organisation that was prepared to think outside the box about how people might want to interact with and learn about the intertwined histories of science and art." - Carys Boughton, intern in the Wellcome Library

“The Reading Room is the first aspect of the Wellcome Trust, or the Wellcome Library specifically, that drew me towards the internship opportunity here. I loved the idea of working for an organisation that was prepared to think outside the box about how people might want to interact with and learn about the intertwined histories of science and art.” – Carys Boughton, intern in the Wellcome Library

Carys Boughton did her internship with Wellcome Library. She is studying for a  BA in History of Art at the University of Cambridge and her highlight was taking a painting from the Wellcome Library’s collection to the National Gallery to be x-rayed. “The results were fascinating!” she told us.

Elizabeth Jones is studying psychology at Durham University and spent her summer with the Neuroscience and Mental Health team at the Trust. She enjoyed the ‘Mindfulness’ press briefing that she attended. “It was interesting to hear more from the researchers about the study and to see how the press covered the project in the papers the next day!”

Emma Dixon is Editor-in-Chief of a student magazine at St Andrews and is about to begin her fourth year of a molecular biology degree. Her internship was with the Editorial team, who look after Mosaic, Big Picture and more. The highlight of her time here was being able to publish content she’d been working on for the last two months!

My highlight has been spending nine weeks meeting incredibly talented people, both within the Trust and external grant-holders, and being able to concentrate on a topic area I really love” says Georgia Threadgold, who worked with the Medical Humanities team during her summer break. The placement complements the history degree that she is studying for at the University of Bristol.

Caitlin Jones Fullerton spent her internship with our Innovations team. “I really enjoyed being able to read award applications and then attend the committees where funding decisions are made” she says. “It was great to get an insight into some of the projects at the forefront of medical research and to hear expert opinions on which projects look promising, where they might fail and the kind of impact a successful application may have on society.”

What did you learn about the Trust?

“Before starting here, I had not realised that the Wellcome Trust had quite so many facets to it” says Carys. “It carries out and takes part in a huge variety of projects, which is testament to how receptive the whole organisation is to different ideas.”  Legal intern Josh Rodger, had a similar realisation, saying “The Trust does not just fund medical research, but also is involved in furthering science through various means whether it is funding films, games or school initiatives.”

Oliver Hurley, who is studying for a business degree at the University of Kent, found out how important the things the Trust gets involved in are to society. “During my internship, the Trust published the news that they had effectively funded a new vaccine for Ebola” he says. “I’ve never worked for such an inspiring organisation that has such amazing impacts on the world!”

Caitlin agrees: “I always knew the trust funded scientific and medical research but I didn’t realise the scope of their impact – from science policy to education and arts funding, and even funding a man to live as a goat for three days!” The scale and global reach of the work that we do at the Trust is on a par with the diversity of projects that we fund and support.

What new skills have will you take away with you?

"My favourite thing is my mug because I was given it on my first day by the leader of my team. I like it so much because it is from the Wellcome Collection shop, it has the periodic table on it and it has been in many a meeting with me (both fun and serious!)" - Sydney Ambrose, Engaging Science intern

“My favourite thing is my mug because I was given it on my first day by the leader of my team. I like it so much because it is from the Wellcome Collection shop, it has the periodic table on it and it has been in many a meeting with me (both fun and serious!)” – Sydney Ambrose, Engaging Science intern

King’s College London Computer Science undergraduate Vincent Truong worked with the Trust’s IT department for his internship. He’s seen a big improvement in his business analysis skills and developed his communication with people during meetings. He’s also learnt “you can’t be afraid of your own opinion”.

Amara Lalemi-Jacobs is taking away a lot of new skills, experience, new friendships and connections from her time with the Education and Learning Team. She’s also keeping her free Wellcome Trust careers season cup as a reminder of her time with us.

Carys tell us she has an even stronger desire to pursue a career within organisations/projects that value multi-disciplinary innovations and a constant focus on self-improvement, while Caitlin says “I now feel more confident in the direction I wish to focus my degree and what to do next when I graduate”.

Elizabeth now has “the confidence and information to start looking at careers I hadn’t even considered before” and Oliver says he’ll take away invaluable knowledge about where he wants to go, and what he wants to do in regards to his career. “My line manager and mentor have been brilliant in making sure I’ve had every opportunity available and getting me to take the initiative and grab them.”

“I’ve learnt so much about the writing/editing/publishing process that I’m sure will help me with the student magazine and beyond” says Emma. Jodie Rogers is studying Psychology at the University of Bristol and she joined the Engaging Science Food and Drink Team. “I have definitely learned more about social media marketing as well as our current unsustainable global food system.”

What surprised you about working at Wellcome?

"My picture is in Rooftops restaurant due to enjoying all the lunches that I have eaten there. As part of The Crunch Team, I felt that I had to find somewhere related to food and drink!" - Jodie Rogers, Engaging Science Food and Drink intern

“My picture is in Rooftops restaurant due to enjoying all the lunches that I have eaten there. As part of The Crunch Team, I felt that I had to find somewhere related to food and drink!” – Jodie Rogers, Engaging Science Food and Drink intern

Cameron Jones, studying classics at University College, London enjoyed the independence that he was given during his internship with the Education and Neuroscience team. “I’ve never had such freedom to work on things in my own way and see projects through to completion” he says. Vincent enjoyed working of projects that have real impact, and Amara was surprised by the range of people working here “from scientists, to doctors, to legal staff – I enjoyed being able to work with such a range of people”.

“Wellcome is the largest organisation I have worked for” says marketing intern Kelsey Cryan who is studying for BSc Management with Marketing at Royal Holloway. “What amazed me was the diversity of roles and scope of areas within the Trust”.

I got the feeling the Trust is really interested in what interns have to say” says Georgia. “They are always asking what we think, what we don’t like and what could be improved, so you feel like your opinions really matter.”

“You hear some horror stories about intern’s just spending hours photocopying or doing tasks that nobody else wants to do, but it’s not been like that here” says Elizabeth. “I’ve been made to feel like part of the team and had my own project to work on.”

“People are so giving with their time” says Oliver. “I was surprised how open all Trust staff members (whom I had the opportunity to interact with) we to engaging and working with interns” agrees Carys.

A lot is expected from you!” says Sydney Ambrose, studying biomedicine at King’s College London. “Your opinions are valued and the work you do will contribute to the work of the team. That made it very exciting to come to work every day and it made you feel like you were making a difference.”

Final thoughts

This opportunity has been amazing, my department could not have been any more helpful and my time at the trust has been so beneficial!” says Kelsey.  “I’ve been transferred into a Trust-ite for sure!” says Oliver.

“It’s made me relax a little bit and look forward to the future rather than dread it” says Georgia. “It feels as though there are lots of opportunities that I now have to take advantage of, rather than viewing graduate life as terrifying and uncertain because now I realise everyone – even the most experienced people – sometimes feel like that.”

We’ve really enjoyed having such a lively bunch of interns with us this summer and we’d like to say a huge thank you to all of them for their hard work this summer!

Our 2015 cohort of interns were: Mohadeseh Abdullahi – AMR Review, Sydney Ambrose – Engaging Science, Carys Boughton – Wellcome Library, Sophie Bracken – Evaluation, Kelsey Cryan – Marketing, Emma Dixon – Editorial, Oliver Hurley – HR, Cameron Jones – Education and Learning, Elizabeth Jones – Neuroscience and Mental Health, Caitlin Jones Fullerton – Innovations, Amara Lalemi-Jacobs – Education and Learning, Fleur Marien-Osborn – Investments, Bianca Mulaney – AMR Review, Josh Rodger – Legal, Jodie Rogers – Engaging Science, Emily Stringer – Finance, Georgia Threadgold – Humanities and Social Sciences, Vincent Truong – IT.

If you’re interested in applying for a summer internship next year, be sure to keep an eye on the internship section of the Wellcome Trust website. We also run a graduate development scheme and offer a range of funding options, including Biomedical Vacation Scholarships.

Wellcome Trust Research Round-up 24.08.15

24 Aug, 2015

Our fortnightly round-up of research news from the Wellcome Trust community…

A breakdown in communication

B0001919 Hippocampal neurons/glutamate receptorsResearchers have identified the possible mechanism in the brains of patients with psychiatric disorders that could be the cause of some of their symptoms.

Many fundamental cognitive functions are reliant on the communication channels between two areas of our brains; the hippocampus and the pre-frontal cortex. Controlled by chemicals called neurotransmitters, these communications drive essential skills like learning and memory and have previously been shown to be disrupted in patients with psychiatric disorders.

Wellcome Trust-funded scientists investigated two neurotransmitters, glutamate and dopamine, which communicate chemical information between the hippocampus and the pre-frontal cortex.

They identified that even subtle changes in the interplay of the two chemicals could have an impact on the communication channel between the two regions. When the receptors for the dopamine neurotransmitters were over-activated, it led to the suppression of the function of the receptors for glutamate – called NDMA receptors.

Overall, researchers observed a significant disruption in communication which could help to explain why the functions governed by these channels are disrupted in patients with psychiatric disorders.

This research is published in PNAS.

Targeting Pulmonary Hypertension

L0004130 The heart, circa 1749.A new drug target has been identified which could offer hope to thousands of sufferers of the life-threatening disease, Pulmonary Arterial Hypertension (PAH).

Caused when blood vessels in the lungs constrict, the disease puts undue strain on the heart which can lead to heart failure. PAH can be caused by low oxygen conditions and is therefore sometimes seen in those that travel to high altitudes. However, a more severe and chronic form of the disease affects around 6,500 people in the UK and leaves patients breathless and exhausted.

Currently, treatment is only designed to tackle the symptoms of the disease and patients have a 30% chance of dying within three years of diagnosis. In research published in Nature, Wellcome Trust-funded scientists have identified a gene that is ‘switched on’ in the lungs of patients with PAH that could offer new hopes for treatment.

The gene, which is not active in people with healthy lungs, is responsible for producing the protein ZIP12, a zinc transporter that regulates zinc levels within cells. Researchers found that disabling the gene helps to protect the lungs from pulmonary hypertension in low oxygen conditions. They hope that developing drugs that act on the ZIP12 protein could provide a solution to reversing or delaying the progression of the disease in chronically affected patients.

Professor Martin Wilkins from Imperial College London, said: “Very little is known about the link between zinc transporters and cardiovascular disease. With this research we show that a gene involved in the way that zinc is transported within our cells is also involved in a chronic illness called pulmonary arterial hypertension. Our research provides a new opportunity to understand how pulmonary hypertension develops and with this find new ways to treat this illness.”

A new approach to combating dysentery

B0008379 Shigella flexneri invading embryonic stem cellVaccines may not offer the most effective solution to tackling bacterial dysentery, according to new research published in eLife.

Shigella flexneri is the leading cause of bacterial dysentery which affects an estimated 165 million people in low-income countries, most of whom are children under the age of five. Researchers from the Wellcome Trust Sanger Institute conducted the largest global genomic survey of S. flexneri to date, using 351 samples of the bacteria from Asia, Africa and Central America.

They found that distinct groups of the bacteria can survive, and are endemic, in certain locations and environments, and have been for many years without being dependent on humans for survival. This finding may explain why they are able to repeatedly re-emerge in an environment and cause disease.

Researchers also found that certain lineages of the bacteria can switch between serotypes (the makeup of antigens it displays on its surface) and evade vaccines based on specific serotypes.

This genomic analysis enables researchers to gain a much greater insight into the bacteria’s evolution and transmission, a vital step in developing more effective interventions. This research highlights the importance of clean water sources, rather than vaccines, as the most effective method of combatting bacterial dysentery.

Nick Thomson from the Sanger Institute said: “By using genome sequencing to study the species at the highest resolution possible, we are able to identify clear lineages of bacteria based on the virulence genes they carry. These lineages can then be targeted more effectively for intervention whether that be through vaccine development and/or alternative strategies.”

In other news…

buddha

Dr Buddha Basnyat

Dr Buddha Basnyat, Director of the Wellcome Trust-funded Oxford University Clinical Research Unit Nepal, this week called for a widespread vaccination programme to combat the growing risk of a typhoid epidemic in post-earthquake Nepal. In an article published in Nature, Dr Basnyat called for an international effort to assist the Nepalese government to purchase the vaccine with the aim of protecting the millions of people affected by the devastating earthquake in April.

Congratulations to Dr Rohan Paul who is named in MIT’s Top 35 Innovators under 35. Dr Paul played a key role in the development of the Wellcome Trust-funded SmartCane device, an innovative and affordable navigation aid enabling safe mobility for the visually impaired.

Image credits: (from top to bottom) A J Irving, Wellcome Images; Wellcome Library, London; David Goulding, Wellcome Trust Sanger Institute, Wellcome Images

Image of the Week: Stinging Nettle

21 Aug, 2015

B0006134 Stinging hairs on a nettle leaf

It’s all part of the classic British summer – picnics, intermittent heat waves, sudden rain showers – and the burning sensation of an unexpected nettle sting.

Our image this week shows the surface of a stinging nettle (Urtica dioica) leaf, in far more detail that can be seen by the naked eye. Using a scanning electron microscope (SEM) an electron beam is passed over the surface of the sample, and incredibly detailed images are produced from the resulting signals.

What we can see in the image above is the surface of a stinging nettle leaf covered in fine hairs. The larger ones deliver the sting, and these stinging hairs are hollow tubes with walls made of silica, making them into tiny brittle glass needles. When you brush past them the tips of these hairs easily break, and their sharp tips pierce the skin, releasing the toxic liquid that causes us to yelp!

At the base of each hair sits a bulb containing the stinging concoction which includes formic acid (the same toxin as an ant bite), histamine (which causes inflammation in the body), acetylcholine and serotonin – the neurotransmitters that get our nervous system firing.

Once stung, you may feel the effects for up to 12 hours, though antihistamine or cortisone cream can help soothe the itching. You may choose to hunt for a dock leaf – long believed to help provide relief from nettle stings – but there is no evidence that these provide anything more than placebos. (The act of searching them out may take your mind off the pain at least!)

While many choose to avoid nettles due to their sting, cooking them destroys their venom and they are used to make nettle soup, nettle tea and even Cornish Yarg cheese!

Nettles have been used medicinally for hundreds of years to treat various ailments including painful muscles and aches, urinary tract infections, hayfever and benign prostatic hyperplasia. Evidence for effectiveness differs for these conditions, and it is important that you don’t self-medicate with nettle as it can interfere with other medications, such as blood thinners, drugs for blood pressure and diuretics.

Image credit: Liz Hirst, Wellcome Images CC-BY-NC-ND 4.0

Wellcome Images is one of the world’s richest and most unusual collections, with themes ranging from medical and social history to contemporary healthcare and biomedical science. Over 100,000 high resolution images from our historical collections are now free to use under the Creative Commons-Attribution only (CC-BY) licence

ISSF: Innovative funding to help universities develop themselves

19 Aug, 2015

ISSF grantsThe Wellcome Trust has many different grant schemes on offer, from small arts awards to multi-million pound funding for Centres of research excellence. The Institutional Strategic Support Fund (ISSF) is a £38m funding scheme over two years to support biomedical research (and related activities), with a bit of a twist – it’s up to the universities who are granted the money to decide how best to spend it. Roger Blake, External Liaison Manager at the Wellcome Trust, explains the benefits of this distinctive scheme…

The usual grant-giving process relies on people or organisations coming to us with their pre-defined ideas for projects and research, and this process works well. However there are some occasions where it is hard for us, as a funding body, to fully understand the individual challenges that universities are faced with and what ‘on the ground’ priorities need to be addressed.

This is where ISSF funding comes in. Funded universities are encouraged to invest strategically in areas of unmet need such as early career support, seed funding and proof of concept studies, public engagement, and collaborative and interdisciplinary initiatives – areas where there may be existing goodwill and ideas, but limited financial investment.

Furthermore, we like ISSF funds to establish institutional structures and strategies that can sustain and facilitate these activities in the long-term.

The awards – of between £600,000 and £3 million over a two year period – are available to UK universities, who are asked to match the allocation with their own funds. This gives an indication that the institutions receiving the money are serious about making investments in these areas and ideas that could benefit generations to come.

The key advantage of this funding is the flexibility and freedom it gives universities to determine how best to use the funds to suit their unique circumstances. This recognises that a “one-size fits all” top-down approach is not always the most effective, and has led to a range of different approaches being developed, a few of which are outlined below.

JF Pink V2

Enhancing interdisciplinary collaboration

The University of Exeter is taking a large-scale, centralised approach to nurturing collaboration between different fields, using ISSF funding to establish and run a Biomedical Informatics Hub within its Wellcome Trust Centre for Biomedical Modelling and Analysis.

The Hub hosts regular exchange meetings to spark ideas for integrated research and foster new collaborations across biomedical, clinical and quantitative sciences.

Smaller-scale approaches can also help foster collaborative thinking, as the University of Leeds is demonstrating with its innovative discipline-hopping programme. This uses some of the ISSF award to provide grants that allow researchers to briefly dip into other fields to gain new insights and perspectives.

Supporting early-career researchers

The Faculty of Health and Life Sciences at the University of Liverpool has introduced a five-year tenure-track fellowship scheme to give early-stage researchers a new career route, with better-protected research time than traditional lectureships. This enables fellows to focus on their research so they are better equipped to compete for external funding at a later date. The posts are funded 50/50 by the faculty and the ISSF, and the success of the scheme means it has been rolled out across the faculty to replace lectureships, and is even being adopted by other universities.

The University of Bristol is using ISSF support to run innovative Clinical Primer Schemes for recently qualified medical doctors and veterinary graduates. These give early-career clinicians the chance to work in a research environment for the first time. Successful candidates undertake a six-month interdisciplinary research project co-supervised by clinical and non-clinical staff at the Elizabeth Blackwell Institute for Health Research. Of the 21 medical Primers funded since 2011, five have secured research training fellowships and three have academic clinical fellowships.

Rebecca Pearson, Bristol University Blue

Like many other universities, Bristol also uses the ISSF to support Early Career Fellowships, helping talented researchers to develop their own research careers in the biomedical sciences, medical humanities and social sciences. Fellows receive funding and mentoring support to enable them to apply to external funding bodies for their own research grants.

Promoting diversity in research staff, the College of Life Sciences and Medicine at the University of Aberdeen is using ISSF support to launch a Supporting Women Returners programme aimed at female academic staff returning from maternity leave or a career break. The programme enables them to apply for three to six months of protected research time so they are in a better position to apply for research grant or fellowship funding, or to publish findings to support their career development.

Public Engagement

The Trust has a range of different support for public engagement activities, and the ISSF can be used to help universities take a more strategic approach to public engagement.

Simon Chaplin Green

The London School of Hygiene and Tropical Medicine (LSHTM) has used ISSF support to appoint a public engagement co-ordinator and establish an advisory committee to help guide their activities. The co-ordinator was instrumental in developing and implementing LSHTM’s new public engagement strategy, which supports researchers incorporating public engagement into their work and provides staff training and individual advice on how to engage with the public and funders.

At a more advanced stage of its public engagement journey, the University of Manchester is using ISSF funding to enhance its already well-established public engagement strategy, having had a co-ordinator leading Public Programmes since 2009. A Public Engagement Advisory Group has been set up to improve decision-making on which projects to fund, liaising directly with the University’s Strategic Operations Group. ISSF funding is being used to develop a more rigorous approach to evaluating public engagement activities – all projects now have to have a built-in evaluation strategy.

Space to innovate

The ISSF gives universities the chance to identify and quickly address priorities and challenges in a way that best fits their current institutional needs. We encourage them to share their progress and ideas so that other universities may benefit from the lessons they have learned about what works.

Having spent time listening to universities across the UK we know that the ISSF is one of our most valued schemes and we look forward to more exciting things to come from it.

You can find out more about the Wellcome Trust’s ISSF funding in this previous blog post. Details of the scheme and a list of the 25 universities who currently receive ISSF grants can be found on our website

Researcher Spotlight: Dr Ivana Rosenzweig

17 Aug, 2015

Dr Ivana Rosenzweig is a Wellcome Trust Career Re-entry Fellow based at King’s College London. As Consultant Neuropsychiatrist she investigates the role of sleep on our brains and the rare and complex disorders that can keep us awake at night…

What are you working on?

I am exploring the role of sleep and hypoxia (i.e. low oxygen) on brain plasticity, with a particular focus on the neurobiology and cognitive effects of various sleep disorders such as sleep apnoea.

Sleep and sleep stages are characterised by specific brain rhythms. These rhythms or oscillations could be broadly explained as the ways brain cells communicate one with another. During sleep, brain rhythms orchestrate memory, emotions and overall brain cells maintenance. Unlike those of wakefulness, sleep rhythms are maintained free of external inputs. This means that any transient input during the sleep can have a lasting impact on how we function, think and feel during the day.

Non-rapid eye movement (nREM) and REM sleep stages can be seen as unique states for any potential therapeutical intervention in memory and brain plasticity, as well as a myriad of neuropsychiatric disorders that have been identified as having a particular sleep stage or sleep “oscillopathy” fingerprint.

What does your average day involve?

I work at several South London sites, juggling clinical and academic duties. It can be stressful, but the truth is that this is exactly how I like it – I feel immensely privileged to be able to combine several roles in my research, each of which presents an important part of working as a clinical scientist.

The research that I do demands a precisely tuned multi-disciplinary effort, and I am fortunate to be surrounded by amazing colleagues from various different fields.

In my clinical role, I work as a Sleep Consultant at one of the biggest sleep disorders centres in the UK, at Guy’s and St Thomas’ Hospitals. We are a small team of highly dedicated and enthusiastic clinicians who see some of the most complex and rarest sleep disturbances in the country.

Dr Guy Leschziner, who is our clinical lead, ensures we rise to this challenge and more importantly, he has also undertaken to establish us as a Centre of research excellence. In order to do so, we recently formed the Sleep and Brain Plasticity Centre at the Department of Neuroimaging.

The idea and the name for this was originally derived from the collaborative research platform that my close friend and colleague, Professor Mary Morrell from Imperial College and I co-established. The need for such a hub of clinical and academic excellence in sleep research in London has been long recognised but never fully materialised. I am delighted that it is now up and running and that I am part of a stellar team.

During sleep the brain structure called the thalamus orchestrates several of sleep rhythms, much like a conductor conducts a symphony

During sleep the brain structure called the thalamus orchestrates several of sleep rhythms, much like a conductor conducts a symphony

Why is your work important?

We spend one third of our life sleeping, and if we for whatever reason stop being able to do so – we know that we will die. Yet we know so little about why that is the case and what happens during sleep with our brain and our body. Also, in the 21st century, we are still ignorant as to how to treat the majority of sleep disorders.

What do you hope the impact of your work will be?

In the short term, I hope that we help gain more insight into what happens in brains of people with sleep apnoea. We have already taken some important steps in that direction and we are shortly going to publish some of our preliminary data that suggest a mechanism behind how that chronic process may act to increase the risk of accelerating the neurodegenerative process in some patients.

The Holy Grail as far as our patients are concerned would be to learn how we could prevent the process from ever starting in the first place.

In the longer term, I have many ambitious new ideas, some of which I am already working on. For example, what if we could help develop therapeutical paradigms and safe technologies to treat memory and neuropsychiatric deficits by enhancing/entraining and/or inhibiting various sleep brain rhythms? What if we could use the know-how we gain from the mechanisms involved in sleep to develop treatments for people in a coma, or to provide an alternative lucid dreaming world for those unable to enjoy this one due to their disability?

How did you come to be working on this topic/in this field?

Serendipity, as is the case with most things in life. Sleep research has always fascinated me, but it was not before I started considering the problem of sleep apnoea and the neurocognitive deficits it causes in some patients that I was hooked.

How has Wellcome funding helped you/your research/your career?

Polysomnography set up

Polysomnography set up

In times of austerity, funding of high risk – but also potentially high gain – ideas and projects is a huge luxury and rarity. Nonetheless, without support for such risky projects, in my mind, crucial steps forward in science will not happen.

The fact that the Wellcome Trust as an independent organisation recognises this and tries to nourish this entrepreneurial spirit in scientists is priceless. This inspires a great loyalty in those fortunate enough to be helped by the Trust – and I personally would like to use this opportunity to thank Wellcome’s amazing team for making me a part of this ever growing family.

Whats the most frequently asked question about your work?

The one that I get asked most is whether we will ever be able to engineer our bodies and brains so that we do not need to sleep. The answer to that one is likely no.

I am personally deeply in awe of nature’s design and I think we should not contemplate sabotaging it – we may find that the price is too high to pay.

Which question about your work do you most dread – and why?

I dread being asked if I regret not staying in basic science. The truth is I am who I am because of my life path and I wonder if I could ask the same questions, or feel so passionate about them, if I were not also a practicing clinician.

Tell us something about you that might surprise us…

I am a decent free-diver and a feisty fencer.

What keeps you awake at night?

Full Moon and quirky research ideas….

Whats the best piece of advice youve been given?

Don’t judge someone just because they sin differently than you.

Never look back, except to learn which patterns not to repeat.

The chain reaction question from previous spotlightee Alex Julyan is this: What constitutes risk in your field of work?

Not being brave enough to swim against the current vogue of thinking.

You can find out more about Ivana’s work by visiting the King’s College website.

Image credits: (from top to bottom) Provided by author; Courtesy of F.Frohlich group; Courtesy of M.Morrell group

Smart phones to the rescue: Detecting the warning signs of blindness in India

14 Aug, 2015

screening 6 (1)

In a country with over 60 million diabetics, and a doctor-patient ratio of only 1:8300, how do you ensure that each patient gets the early screening needed to help prevent vision loss?

In India, scientists hope to be able to counter the growing problem of preventable blindness thanks to a new ultra-portable lightweight device that is able to detect any early signs of sight deterioration.

Developed by Remidio Innovative Solutions in Bangalore, the Fundus on Phone (FOP) device is able to ‘piggyback’ onto a regular smartphone and take high resolution images of the back of the eye.   Designed with simplicity in mind, the images can be taken by local health workers in the field, before being sent electronically by WhatsApp and Gmail to ophthalmologists many thousands of miles away to look for early warning signs.

Funded by the Wellcome Trust under the Affordable Healthcare in India scheme, the idea for the innovative device actually came after a chance meeting with an ophthalmologist on a train. Founder and Director of Remidio Dr Anand Sivaraman explained how the ophthalmologist talked of the problems of preventable vision loss and that despite the treatment costing only $30-50, the instruments needed to detect it can cost up to $100,000. Dr Sivaraman immediately saw the need for cheaper better technology and the first prototypes were built by hand in the kitchen of his partner, and co-founder, Pramod’s design studio.

Pilot programs have already shown the potential public health impact this technology could have.  Over the past 18 months over 3800 diabetics in Maharashtra were screened using FOP by women volunteers with no prior knowledge of retinal imaging, under the clinical guidance of Dr Salil Gadkari of Vision India Foundation.  Of these, 507 patients were found to have sight-threatening retinal conditions that they were not even aware of, which means that 13% of the screened diabetics were potentially saved from permanent blindness due to a simple retinal image taken on a smartphone.

Dr Sivaraman says: “Early detection is key in the war against preventable blindness caused by chronic conditions such as Diabetic Retinopathy, ARMD and Glaucoma. Large scale screening requires devices that are not only affordable, but also simple to use, easy to maintain and reliable.  Given its simplicity, affordability and ease of use, FOP has the potential to significantly impact preventable blindness programs, through tele-ophthalmology-based screening, globally.”

To find out more about the Fundus on Phone technology visit the Remidio website.

Image credit: © Remidio Innovative Solutions Pvt Ltd

How to conduct a clinical trial during a disease outbreak

11 Aug, 2015

Ebola Lang 2

A year after the WHO declared the Ebola outbreak to be a health emergency, new cases continue to emerge in Guinea and Sierra Leone. Oxford Professor of Global Health Research Trudie Lang is part of a team that has been carrying out clinical trials of potential Ebola therapies – some of the first to ever be conducted in the midst of an epidemic. In a follow up to a recent commentary piece for Nature, she shares some of her tips for designing and operating a clinical trial during a disease outbreak…

Clinical trials are cumbersome and difficult in any setting. They take a long time to set up, are highly regulated and are (although they don’t always need to be) expensive.

Within the context of an infectious disease outbreak, such as Ebola, meeting the existing challenges while trying to set up a trial within the narrow window where cases are available is very difficult. Indeed, during all previous disease outbreaks, including the recent MersCoV and H1N1 outbreaks, not a single trial was conducted and we are still left with no proven treatments or management strategies for these infections.

When Ebola hit West Africa last year, it soon became apparent that here was an opportunity to do what nobody had managed before – to carry out ethical, safe and scientifically robust clinical trials of promising new treatments and vaccines in the midst of an epidemic. For our team at the University of Oxford, the learning curve was steep, but we quickly gleaned some valuable lessons that we should all take forward for the next, inevitable, infectious disease outbreak.

Do as much as you can in advance of an outbreak

It took our team an unprecedentedly short 12 weeks to line up everything we needed to begin trialling our first experimental drug, the antiviral brincidofovir. This was thanks to a huge collaborative effort between multiple agencies. But we should have been quicker, and could have been if we’d had trial protocols agreed and approved before the outbreak started.

Research needs to be considered at the outset of an outbreak and then requires an agile and streamlined approach to getting the trials designed, set up and operated in order to obtain much needed data within a short window. Even better if that research can also be embedded within the medical humanitarian response.

This requires leadership from the WHO and a better grasp of the realities of research (and its requirements) from all the agencies involved.

Ask the right questions

Whether it is determining whether a drug or vaccine works in a disease, or evaluating how best to manage and care for the patients, you require a clinical trial.

The starting point – and the key to it all, in my view – is having a single clear question such as “Does drug A reduce mortality at day Y?” or “Does survival improve if fluids are given to all patients on admission to a centre?”.

Devise a clean and pragmatic protocol that will give you an answer quickly

Evaluating drugs during the Ebola outbreak taught us that the one thing you don’t have during an epidemic is time. With the rate of new cases now (thankfully) in decline, one of the biggest challenges we faced was devising a study protocol that could quickly tell us whether or not an intervention was working.

Having your research question is the first step, but developing a good research protocol is key to being able to answer that question accurately, safely and ethically. My mantra here is keep in simple, only measure anything that you really need in order to answer the question. If what you are doing or measuring (within the trial) is not going to contribute – then don’t do it.

Have a dress rehearsal

With the Wellcome Trust funded trials that we led in Liberia and Sierra Leone during the Ebola outbreak we went through a ‘trial walk-through’. This is an approach that I always take when trying to turn a question into an operating trial, especially in low-resource and challenging settings such as this.

It allows us to think about each patient and remember that they are the centre of all this. You have to consider what happens to them through their clinical care within that setting.

It works really well to literally map out what happens to each patient, when their blood samples are taken and where they go and what data are we collecting at what time points. It highlights logistical, ethical and design issues before we start, and gives us a chance to work out how to overcome them.

These could be questions such as “at what point can consent happen and where?”, “how will the samples be transported?” or “how do we verify patients are alive at days 7, 14 and 28 if they have returned home?” For all these practical challenges we have to find locally workable solutions, such as sending the participants home with a new mobile phone.

Walking through one of our trial protocols

As you can see from the image above, our ‘walk through’ wasn’t exactly high-teach, but it was a highly effective method of establishing what we needed in terms of clear operating procedures, trial staff and what points might be difficult.

Develop local research capacity

Clinical trials are rare in low-resource settings and indeed previous research experience was low in all the countries affected by the Ebola outbreak. We made a strong effort to train the local health-workers in basic research skills and awareness.

One of the partners in our efforts with this trial is The Global Health Network, which is an online science park that aims to improve and encourage research in places and situations where evidence is lacking. Using the Global Health Network, we are planning to hold research skills sharing workshops in Sierra Leone, Guinea and Liberia.

The aim here is to take the experience of working on the Ebola drug and vaccine trials and use it as a basis for showing the importance of research and encouraging the development of local research capacity.

Engage with the community

In the early stage of any planned research it is key to inform and involve the local community where the studies are being conducted.

In the case of Ebola trials this was incredibly difficult and sensitive due to the level of fear in the community and mistrust of the health service. For this trial we worked with the local agencies and thought carefully about how to explain the concepts that we needed to make sure were clearly understood in order that the trial was accepted.

Share your data

Data sharing is so important in order to generate the most benefit from clinical studies. Normally this is difficult because investigators are reluctant to share, and because they have all collected data in different ways. During the Ebola outbreak we achieved something quite special. We adapted the ISARIC data capture form into our trial-specific data forms, as did other trial teams, so the data could all be shared more easily, ready for new analysis to be conducted by other groups.

Remember the common goal

In an outbreak on this scale, with multiple agencies from different parts of the world established in different areas it was always going to be challenging to coordinate research on the ground.

We need to change from research being an afterthought in humanitarian crises, and instead get used to embedding research as a standard and expected element of the medical humanitarian response.

Expect the unexpected

Ebola LangAs with any trial, the team faced unexpected challenges and situations that we could not have anticipated. These included issues such as how to secure the drug supplies (in terms of getting them into country and also keeping them safe in the centre) and what would happen if one of the staff became sick.

The most important thing is to keep in mind the question you are trying to answer. That way you can work through each unexpected eventuality and consider it in terms of how it impacts the safety of the patient, the reliability of that specific data point, and whether there are there any ethical implications. Thinking through these three key elements will help guide you on whether – and what – action is needed.

Final Reflections

When we did get up and running, our experience in the treatment centres run by Medicins Sans Frontieres and GOAL, was an overwhelmingly positive one.

The teams that we sent out to run these trials did an incredible job in highly challenging settings that put them at considerable personal risk, and they should be recognised for their impressive and dedicated efforts.

We feel we have achieved something remarkable – we successfully set up two clinical trials in two countries (brincidovofir in Liberia and TKM-Ebola-Guinea in Sierra Leone) within the narrow window of a disease outbreak, and we managed to complete one of them and answer the question that was set.

This work proves that trials can be done in these difficult circumstances and hopefully raised awareness of the importance of trials to governments, donors and health agencies. Let’s hope that the lessons we’ve learned mean that next time we really are more research ready.

You can read Trudie Lang’s commentary piece in Nature’s special Ebola issue and find our more about the Wellcome Trust’s Ebola Research Fund on our website. More information can also be found on Ebola Clinical Trials platform website.

Wellcome Trust Research Round-up 10.08.15

10 Aug, 2015

Our fortnightly round-up of news from the Wellcome Trust Community

Virus-cell interactions unravelled

B0006938 Common cold virusNew Wellcome-Trust funded research has found that our cells are able to use the viruses that infect them to transport a protein that encourages a stronger immune response, which could lead to the design of more effective vaccines.

When a virus that either contains or produces DNA enters our cells it is detected by a protein called cGAS. This initiates a signalling cascade whereby cGAS produces a small messenger molecule known as cGAMP which stimulates our immune systems to mount a response.

In new research published in Science Express, scientists found that when a virus replicates within our cells, it incorporates small amounts of the cGAMP molecule. Therefore, when the virus enters a new cell the cGAMP immediately triggers an immune response. Viruses from cells producing cGAMP stimulated much more potent immune responses when infecting new cells than viruses from cells unable to produce the molecule.

Researchers are hoping that these findings could help to improve vaccines that use viral vectors, which are designed to promote an immune response against disease. By loading the genetically engineered virus particles with cGAMP a stronger immune response could be triggered, resulting in more effective vaccines.

Wellcome Trust Investigator Professor Jan Rehwinkel from the MRC Human Immunology Unit explained: “We hypothesised that as the virus replicated, cGAMP was incorporated and carried to the next cell to be infected. This may not have been spotted before because in the lab researchers tend to use cells that are free of cGAS and therefore unable to produce cGAMP… It is not yet clear whether cells are tagging these virus particles deliberately or whether it is simply a by-product of how viruses replicate.”

Genetic testing breakthrough for diabetes

7015509987_1ec05e3a0b_zTreatment for children with rare forms of diabetes has been revolutionised thanks to a huge reduction in the time taken for genetic testing to take place.

Previously, it took up to four years for a child who had been diagnosed with diabetes to receive genetic testing. In the past ten years this time lapse has fallen to less than two months, allowing patients to receive the best and most appropriate care as soon as possible.

Doctors no longer use the baby’s symptoms to select which genetic cause of diabetes to test for, but are now able to test for all 22 possible causes at once, further speeding up the full diagnosis.

Rapidly identifying the underlying genetic cause of the disease allows doctors to anticipate any potential healthcare problems that may occur in the future, and plan for these accordingly.

Faster diagnostics is especially essential for the 40% of diabetes patients who have a mutation in the genes for a potassium channel in pancreatic cells. By swapping their insulin injections for sulphonylurea tablets these patients are able to have much better control over their glucose levels.

Professor Andrew Hattersley, a Wellcome Trust Senior Investigator at the University of Exeter Medical School, said: “In the last decade, we have shown that making a precise diagnosis from genetic testing results in improved treatment and hence we now get samples soon after diabetes is diagnosed from patients throughout the world.  Now the ability to test all genes in a single test means we are able to accurately inform patients and their doctors – not just about the best treatment but also about likely medical problems before they have started.

This research is published in The Lancet.

In other news…

Talking about drug resistant infections

Tackling the rise of antimicrobial resistance is one of the biggest challenges of modern times and an issue too big to ignore. We frequently see headlines quoting ‘millions more deaths’ or ‘trillions of pounds’ but does this actually mean anything to the public?

Screen Shot 2015-07-29 at 12.00.53

A response from a participant

The Wellcome Trust recently commissioned research into public attitudes towards antimicrobial resistance, with a major finding being that the language used by the media and scientists is confusing and can leave them feeling distant from the issues. By getting a clearer sense of people’s attitudes, and what had led them to believe these things, we will be able to better our communication around this complex issue.

To find out more about the research and results you can read a previous blog post on the issue here.

Applications now open

Would you like to help shape our funding portfolio? The Wellcome Trust are now recruiting for new members of our funding committees, the groups that form an essential part of the decision process for awarding grants.  We want to increase the diversity of members on these committees so are inviting researchers with excellent track records in their discipline to apply to join. Find out more information in a previous blog post or apply online on the Trust website.

Some of the most highly prized investments in the Wellcome Trust portfolio are the Centres, which bring together people from different disciplines to undertake innovative research. There are currently eight specialist centres, from mitochondrial research to neuroimaging, as well as four Centres of Excellence in Medical Engineering. Last week, Wellcome Trust Director Jeremy Farrar announced an open competition to create new Centres across the UK in all disciplines we fund – this includes social sciences and translational research. Find out more about the Centres competition in a previous post and about how to apply on our website.

Image credits: (from top to bottom) Anna Tanczos, Wellcome Images; The touch of hands by Alex Prolmos via Flickr, CC-BY-NC

Image of the Week: Thank you science!

7 Aug, 2015

Alphanso Appleton's wonderful image

You might have already seen this week’s chosen image doing the rounds on social media earlier in the week, but we thought it was important to share the story behind the photo, and the Liberian photographer who took it. Following last week’s publication of remarkably positive results from the VSV-EBOV Ebola vaccine trials we were sent this image, which the photographer Alphanso Appleton kindly allowed us to share. His story makes this wonderful photo even more powerful…

Alphanso Appleton holds up a his written permission to use the image.

Alphanso Appleton holds up his written permission to use the image.

I am Alphanso Appleton, and I live in Robertsport, Liberia. I am 23 years old, and I am the son of an Ebola survivor.

I saw on Facebook on my mobile phone that a vaccine for Ebola had been created. I called my friend Cori Stern, who works with an organisation called Strongheart, to ask if it was real and she said it was true. It was very real and been proven by science.

I started telling everyone in our area. We are all so excited about it. I was so happy, I made a sign to say thank you to science! I took the photograph of my neighbour – six year old Cecelia – in Kru Town Village, Robertsport.

Ebola has affected my country so much. I was so afraid when my mother was sick. She was lucky enough to survive though. Sadly many people weren’t. The vaccine is science – and a miracle.

Ebola has also affected many things beyond just health in Liberia. My dream is to study photography and I was accepted into a school in the US to begin my studies. But when Ebola happened, the school decided not to allow any Liberians to come. I was just accepted by a wonderful new school but am worried it will not really happen. It’s not easy for a young Liberian to receive permission to study in the US, even with a scholarship. Maybe now with the vaccine, Liberia will be seen in a stronger way and more opportunities will happen.

I am grateful that my photo has been seen around the world because I think it is important that Africans have a chance to tell our story – including through photos of important events.

…maybe my photo will help young Liberians know science helps the world and become scientists too.

Almost all photos of Liberia used in world news are taken by non-Liberians. I hope to help change that one day with my efforts – and maybe my photo will help young Liberians know science helps the world and become scientists too.

The world needs art AND science working together.

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