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Launching today: our new website!

25 May, 2016

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Today we launched our new website. It has been designed to put our users’ needs first, be accessible to all, work well across all screen sizes and better serve our international audiences.

As explained in Mark Henderson’s previous announcement, the new site will make it easier to find the information that you need. We will also continue to evolve the site to make it work better for users.

Our new website allows us to regularly post content in a way we haven’t been able to before. The content what would have previously been posted on this blog will now appear on the News section of the new website. This blog will still remain online, but no new content will appear after this post. You will still be able to access all old articles and links will still work.

Wellcome Trust Grant Tracker is not changing, nor are any other Wellcome websites.

You can still find us on:

We want to know what you think of our website and your feedback will help to guide our future work to improve it. Please send your thoughts to webmaster@wellcome.ac.uk.

The future of Innovation at the Wellcome Trust

24 May, 2016

Steve.jpgLast year, Stephen Caddick joined Wellcome as Director of Innovation. He has spent the last 12 months listening to staff, researchers and the wider innovation community to gather opinions about how we can best support innovation activities to improve human health. Ahead of the launch of Wellcome’s Innovation strategy later this year, he gives us an update on the new approach and the implications for some of our existing funding schemes.  

In my previous life as the enterprise lead for UCL, I had the privilege of supporting many great entrepreneurs and companies, and to set up a venture from my academic lab. I also saw many promising ideas flounder because of a lack of early phase support and encouragement. I was therefore excited by the opportunity to take up the role as Director of Innovation for Wellcome, an organisation with a track record in helping people turn their discoveries into innovations that improve human health.

Over the past decade, Wellcome’s Innovations team has built an exceptional portfolio of translational projects, and earned a deserved reputation for helping scientists from around the world take those first challenging steps along the daunting road to commercialisation. Our role during this time has been as a gap funder, helping entrepreneurs in universities and companies to reach the stage where their products could be taken forward by other investors.

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The Fundus on Phone device is able to ‘piggyback’ onto a regular smartphone and take high resolution images of the back of the eye © Remidio Innovative Solutions Pvt Ltd

It has proved a successful approach. To date we’ve supported the development of some 30 new products and helped a similar number reach the clinic. Devices, drugs and technologies we’ve funded are being used today by doctors and patients in India, Africa, South East Asia and here in the UK. It’s a privilege to have inherited such an impressive legacy.

C0027328 Chlamydia Rapid Test

A rapid DNA dipstick for detection of Chlamydia trachomatis

We should be extremely proud of all we’ve achieved to date, and I think we can build on this to be even more ambitious. Since joining Wellcome, I’ve been working with colleagues inside and outside the organisation to develop a new strategy for Innovation – one that places a greater emphasis on long-term impact.

With so many successes under our belt, you could be forgiven for asking – why change? But the world of innovation has changed, and there are now many other gap funders – public funders, private investors and corporations – operating in the early translational space. Yet few of these organisations have the freedom to pursue innovation with the sole aim of improving lives.

Wellcome is rare in that respect. Our financial independence gives us the freedom to take on problems others would find very challenging. We could do almost anything, but we can’t do everything. In future we will consider working earlier and later in the translation pathway, but we will focus on a much smaller number of themes where we think we can make a real difference.

We recognise too that one of our great strengths is our flexibility, and we will retain the ability to advance ideas in a small number of activities outside those that fit with our priority themes. It’s an approach that aligns closely with Wellcome’s strategic framework, which we launched in 2015.

It’s still a work in progress. I hope to be able to share the full details of our new approach later in 2016, but in the meantime I wanted to give an update on some of the key elements of our new strategy ‘Innovation for Impact’:

  • Building better links between science, technology and innovation. We will remove barriers between these disciplines to make it easier to take the first translational step. We may play a more active role in supporting technology.
  • Creating a global community dedicated to innovation for impact. We will tap into our international network of companies, supporters and expert advisors to help encourage people from outside the life sciences to engage in biomedical research and innovation.
  • Supporting the next generation of innovation leaders. We will work with emerging innovation leaders, giving them support and access to mentorship through interaction with our global network. We hope to encourage a greater diversity of career paths for scientists by helping them to engage in translation and innovation at an earlier stage in their career.
The SmartCane™ brings safe and independent mobility for the visually impaired at an affordable cost

The SmartCane™ brings safe and independent mobility for the visually impaired at an affordable cost

Our new direction inevitably means making some changes to our existing funding schemes, which will transition to the new approach over the next nine to 12 months. We will do all we can during this time to minimise disruption for our grant holders and new applicants, and I’m confident that, once up and running, our approach will allow us to make decisions more quickly than we have done before.

With our new strategy in place, our primary purpose remains unchanged. We will continue to work with talented people from around the world to transform great ideas, discoveries and inventions into preventions, treatments and cures for disease. We cannot achieve any of our aims on our own. We’ll still need your time, energy, advice and commitment so that together we can achieve innovation for impact – to improve people’s lives. We’re grateful to all those who have supported us to date, and look forward to the next exciting chapter.

If you have any questions or comments please email the Innovations team on innovations@wellcome.ac.uk.

Eight ways we’re improving mental health

21 May, 2016

B0007880 Diary Drawings: Day 104

In the UK 1 in 4 people will develop a mental health condition, and three quarters of these people will receive no treatment. In low and middle income countries treatment rates are even lower.  

This Mental Health Awareness Week, Dr Raliza Stoyanova, our Neuroscience and Mental Health Senior Portfolio Developer, explains eight approaches we’re taking to help people living with these debilitating, but little understood conditions…

  1. Access

When we know treatments work, it’s vital that people can access them. Decades of research we have funded led to enhanced cognitive behavioural therapy (CBT-E) being recommended as a treatment for all eating disorders in the NHS. We’ve also supported a new form of online training for therapists to deliver CBT-E so that the treatment can be implemented quickly.

  1. Task-shifting

Diagnosing and treating mental health conditions is a particularly big challenge in low and middle income countries, where resources are scarce. We hope ‘task-shifting’ – when skills from mental health specialists are taught to non-specialists – can tackle this. We’re funding a project in Goa to train non-specialist health workers to deliver psychosocial interventions, including yoga and interpersonal therapy, to help young people with mental health problems.

  1. Prevention

B0008487 DepressionJust as physical training is associated with improved physical health, we think psychological resilience training could lead to better mental health outcomes, and prevent mental health conditions. To test the theory we’re funding a large-scale trial studying the effectiveness of mindfulness in nearly six thousand 11-13 year olds across the UK.

  1. Genetics

We know that someone’s genetic make-up can play a part in why they develop a mental health condition. The discovery of the first robust genetic links to depression came from a study we funded of Chinese women with and without depression.  It will take a long time and much more research, but we hope studying the genetic variants will reveal new biological pathways in the brain that could be targeted by new therapies.

  1. Subtypes

There are many combinations of symptoms and risk factors that all lead to the same diagnosis of depression. We’re funding a large study in Scotland to understand whether there are actually different subtypes of depression, and why some people develop the illness while others don’t.  With a better picture of these subtypes we can improve diagnostic tests, and develop more tailored therapies.

  1. Technology

Technology can have an enormous impact on mental health conditions. A project we’ve funded found that computer avatars could help people with schizophrenia who still hear persecutory voices despite taking antipsychotic drugs.  Another project we funded shows that playing Tetris can reduce flashbacks of traumatic events, and may be a promising treatment for post-traumatic stress disorder.

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  1. Drugs

Developing and testing new medicines to treat mental health disorders is very challenging – we can’t routinely biopsy a patient’s brain, and we can’t make animal models that completely mimic mental health disorders. We now think there’s a promising link between the immune system and depression, so we’re helping to fund a study to see if re-purposed anti-inflammatory drugs might help to reduce the symptoms of depression. If this approach works, there is an added benefit in that such medicines could reach patients quickly because they are already approved for human use.

  1. Education

It’s crucial patients feel the benefits of cutting edge neuroscience and mental health research as quickly as possible. To do this we’ve helped to fund a project to make sure the curriculum for trainee psychiatrists is up to date with the advances of basic and clinical neuroscience. This will help clinicians embrace current and future developments in the diagnosis and treatment of mental health conditions.

Image credits: (from top to bottom) Diary Drawings: Day 104, Bobby Baker, Wellcome Images; Depression, Stephen Magrath, Wellcome Images ; Diary Drawings: Day 403, Bobby Baker, Wellcome Images

Coming soon: Wellcome’s new website and brand

20 May, 2016

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Mark Henderson, Head of Communications, gives us a preview of the upcoming launch of our new website and updated brand.

For many of the people Wellcome works with, visiting our website is the first contact they will have with us. As someone who is often in a hurry and usually on the move I’m aware of how essential it is that people can easily find what they are looking for and immediately get a sense of who we are.

Our website should be where we communicate Wellcome’s mission and encourage those with great ideas to work with us. It should showcase the breadth of the work we support in accessible, engaging and creative ways. It should also help people find and understand our policies and practices when it matters to them.

Our current website doesn’t do this as well as it could, and we want to put this right.

What’s changing?

Next week, our current website – wellcome.ac.uk – will be replaced by a completely redesigned site that has been built to work better for the people who visit it.

The new site’s design was informed by what people told us was wrong with the old one and what they said they’d like our site to be like. The new site has been designed to be accessible and work well across all screen sizes. While we built the site, an external agency did regular usability testing, to check that it works for users in the ways they want.

We know that it won’t be perfect right away. When the site launches we will be able to see how well it works for users – you! – in the real world. We will continually work to improve and evolve it, adding features and content to make it even better. If you find something that doesn’t work quite right – perhaps a broken link or something that doesn’t read correctly – just contact us and let us know. We may already be working to fix it, but if not, we will address it quickly.

Alongside building our new website, we have also been redesigning our brand – and the new website is one of the first places to feature it. We’ve designed the brand to reflect the diversity and creativity of contemporary science, to work well in digital channels, and to help connect the different types of work that we do. It is much more flexible too – we hope you like it.

On the same day we launch the site we will update our brand on our social media and other digital channels. We’ll then apply it to our non-digital materials and our sub-brands over the summer. For more information about our updated brand, look out for an upcoming news article once the new website is live.

What isn’t changing?

Many users of our current website have links saved as bookmarks or published in documents. These links will still work, with users sent to the most relevant page on the new site.

The following will not be affected:

  • Wellcome Trust Grant Tracker
  • Any ongoing applications for funding or job applications
  • All other Wellcome websites

What’s happening to this blog?

The News section on the new site will allow us to regularly publish high-quality content in a way that we are currently unable to. Much of the content that would have previously been published on this blog will now be published on the new site.

The blog will still remain online, but no new content will appear after the new site launches. You will still be able to access all old articles. Existing links to the blog will still work too.

This blog published its first article in June 2008, on the work of osteologists and what skeletons can tell us about the history of London. Nearly eight years and two million views later, we’ve published 1,517 articles on everything from the success of the Ebola vaccine to the ethics of labiaplasty.

Thank you to everyone who has contributed articles and ideas, shared our posts, and shown so much enthusiasm for the breadth of our work.

What do you think?

After the launch, we want to hear from you. Please send your comments and suggestions to webmaster@wellcome.ac.uk. We’ll get back to you as soon as possible and your feedback will help to guide our future work to evolve our new website.

Image of the Week: Female torso

20 May, 2016

L0019727 Gautier d'Agoty, mezzotint ecorche female torso, back, 1746

This week, Catherine Draycott, Head of Wellcome Images, picks out her favourite image in the collection. 

This image captivated me the moment I first saw it over 20 years ago.  Obviously, it has a very strong initial impact; at first it seems as if the woman is wearing a high collared cape. As you look at the image, the detail emerges revealing her back as viciously flayed open from orbit to sacrum showing the ribcage and muscles of her back whilst she, apparently unperturbed, glances nonchalantly over her shoulder.

The artist was working with an anatomist, J. F. Duverney (d 1748), to produce these amazing colour prints working from the anatomist’s dissections.

Gautier d’Agoty had learned the three colour technique, the first of its kind, from Jacob Christoph le Blon (1667-1741) with whom he worked as an assistant. D’Agoty added black to the three colours, giving greater depth and shading to the resulting prints and resulting in a much more lifelike appearance, especially when used for a subject such as this.

The prints have a velvety quality with none of the harsh lines of etching or other forms of engraving. Along with the depth of naturalistic colour, this conveys the fleshy depths and surfaces of the human body in a way that had never been done before and also allowed it to be reproducible in a printed volume.

Other work by d’Agoty is available in the Library and on the Wellcome Images website.

Credit: Jaques-Fabien Gautier d’Agoty, Ecorche figure showing the muscles and bones of a woman’s back, mezzotint colour print 1746.

 

Image of the Week: Apothecary jar

13 May, 2016

L0058349 Albarello drug jar for Mesue's French Musked Lozenges of Alo

Clearing our throats for International Cough Drop Day*, we bring you a beautiful apothecary jar from Henry Wellcome’s collection, made in Sicily between 1601 and 1630.

Its inscription translates from the Latin as ‘Mesue’s French Musked Lozenges of Aloes Wood.’ These lozenges were pressed from a mixture of aloe wood, ambergris and musk. Ambergris is a greasy substance excreted or coughed up by a small number of sperm whales to clear their stomachs of squid beaks.

Like musk, it is difficult to obtain in large quantities which explains in part its extraordinarily high value – ambergris was reputedly equal to gold in London’s medieval ports. Despite the development of synthetic replacements its complex aroma makes it a prized fixative still for perfumiers.

These lozenges were believed to strengthen the brain and heart and, as the ingredients are very fragrant, they also acted as a deodorant and breath freshener. The preparation had greatest popularity in France.

Mesue (777-857 CE) was the European name for Yuhanna Ibn Masawayh, a prominent Christian physician who wrote in Arabic. Ibn Masawayh worked at the Baghdad hospital and was personal physician to a number of Caliphs.
pastile 2If you prefer your historical lozenges with a little more kick, we might refer you to these Allenbury’s Throat Pastilles (No.63) from the 1920s, whose key ingredients – diamorphine and cocaine – were available in pharmacy cough drops, with diminishing strength, through to the 1960s.   Or perhaps Dr Seth Arnolds Cough Killer, whose death-dealing claims lay in its generous lacing with morphine.

*There is some debate about whether International Cough Drop Day exists. We were led to believe this by someone else, but it’s OK because it’s also National Blame Someone Else Day.

Clinical Research Career Development Fellowships: a new single, flexible award

10 May, 2016

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Back in November 2014 we at Wellcome announced some changes to our funding structure, with a focus on simple, flexible award schemes. Today, one of the  last pieces of this new structure falls into place, with the introduction of a single award for clinical research fellows, the new Wellcome Clinical Research Career Development Fellowship. Here, Anne-Marie Coriat, Head of Research Careers, explains the change, and how we hope this provides a better offer to clinical researchers…

Embedding research alongside healthcare is key to understanding the biological basis of disease, driving medical innovation and developing cutting-edge treatments. At the same time, we understand that being a clinical researcher can be challenging, with many different competing demands – including time in the lab, completing a clinical specialism and maintaining a work-life balance.

We have spent a long time listening to the community, both through individual meetings and through workshops with the directors of the Wellcome Clinical PhD Programmes, clinical trainees, funders, medical school deans and others. One of the key outcomes from this process was to make sure that Wellcome is working with other funders, NIHR, the Academy of Medical Sciences to develop a clear, supportive and connected framework for clinical academic research so that together, we can ensure the best career development for this critically important group of researchers.

In July last year we explained that we had updated our thinking on how we could better support clinicians who want to pursue a career in research. In November 2015 we launched the new clinical PhD programme and we are now delighted to launch the Wellcome Clinical Research Career Development Fellowships. This fellowship consolidates two of our existing schemes into a single, flexible award. and complements the changes we have already introduced for our basic science fellowships.

The Clinical Research Career Development Fellowship provides the option of longer-term support and a greater ability to balance research and clinical training responsibilities. The scheme is open to those who are re-entering academia after career breaks or extended periods of clinical training, and will adapt to the evolving clinical training model.

Our primary aim in making these revisions is to provide flexible support for the next generation of clinical academics.

Key features of the new scheme

  • the Clinical Research Career Development fellowship can be held for up to 8 years in total, split into two stages separated by a flexible but competitive “gate”
  • no stage will be longer than 5 years of full time funding and each will be peer reviewed
  • all components can be completed part time or pro rata
  • time to work overseas or in laboratories outside of your home institution can be included
  • at the time of initial application, you will need to estimate when you intend to apply for the gate; this can be adjusted annually, depending on progress through Phase I.
  • neither phase can be held for longer than 5 years (pro rata) and the total length of fellowship support cannot exceed 8 years (pro rata)

As ever, we welcome feedback on this change – please email sciencegrants@wellcome.ac.uk with any comments or questions.

More information about eligibility for the Clinical Research Career Development Fellowship is available on the Wellcome Trust website.

Wellcome Trust Research Round-up: 09.05.2016

9 May, 2016

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

Lardy Labradors

12356609375_914ea8d014_zLabradors may be prone to becoming overweight due to a newly identified gene variant that is associated with obesity and appetite.

The UK’s most popular dog breed has long been associated with obesity, despite their diets being controlled by their owners. Wellcome-funded researchers studied 310 dogs to identify the presence of three possible obesity-related genes. They also questioned the owners about their dogs’ behaviour to assess ‘food motivation.’

The researchers found that one gene variant – called POMC – was very strongly associated with weight, obesity and appetite in these dogs. For each copy of the gene variant the dog carried, they were on average 1.9kg heavier than their counterparts without it.  The gene this variant affects is also known to play an important role in how the brain recognises hunger and feeling full in humans.

The findings go some way to explaining why Labradors make such good working dogs; they are often trained with food as a reward and this gene variant could make them more motivated to work for it.

Professor Stephen O’Rahilly, Co-Director of the Wellcome Trust-Medical Research Council Institute of Metabolic Science explains how the results of this study could also have implications for humans:  “Common genetic variants affecting the POMC gene are associated with human body weight and there are even some rare obese people who lack a very similar part of the POMC gene to the one that is missing in the dogs. So further research in these obese Labradors may not only help the wellbeing of companion animals but also have important lessons for human health.”

This research is published in Cell Metabolism.

Beneficial bacteria

B0006260 SEM of E.coli 0157 Credit: Debbie Marshall. Wellcome Images images@wellcome.ac.uk http://wellcomeimages.org Scanning electron micrograph of Escherichia coli 0157, showing many individuals Scanning electron micrograph Published:  -  Copyrighted work available under Creative Commons by-nc-nd 4.0, see http://wellcomeimages.org/indexplus/page/Prices.html

Scientists at the Wellcome Trust Sanger Institute have grown and catalogued more than 130 bacteria from the human intestines to help us understand how they keep us healthy.

In research published in Nature, scientists have developed a method to culture these bacteria in a laboratory. Until now this had been a difficult process as many of the bacterial species are sensitive to oxygen.

Approximately 2% of a person’s body weight can be attributed to bacteria, and imbalances in this microbiome can lead to syndromes and diseases like Irritable Bowel Syndrome, allergies and obesity. By culturing these essential bacteria in a lab, scientists can sequence their genomes and try  to create tailored treatments using specific bacteria.

Dr Trevor Lawley, group leader at the Sanger Institute said: “Being able to cast light on this microbial ‘Dark matter’ has implications for the whole of biology and how we consider health. We will be able to isolate the microbes from people with a specific disease, such as infection, cancers or autoimmune diseases, and study these microbes in a mouse model to see what happens. Studying our ‘second’ genome, that of the microbiota, will lead to a huge increase in our understanding of basic biology and the relationship between our gut bacteria and health and disease.”

Storing memories

B0007285 Human brain cellsMemories are replayed and stored in a different part of the brain to where they are formed, according to a new Wellcome-funded study in rats.

The team studied ‘place cells’ in the rats’ hippocampus, an area of the brain important for forming memories, and in the ‘grid cells’ of the entorhinal cortex. The Rats’ brain activity was monitored as they ran along a track for 30 minutes, before resting for 90 minutes.

Activity in the place cells showed the rats replaying their movements on the track in their mind at speeds 10-20 times faster than reality. This activity was also seen with only a 10 millisecond delay in grid cells in a different area of the brain, suggesting that memories are transferred quickly from one area to another.

The study, published in Nature Neuroscience, suggests that replaying memories during rest is essential for consolidating memories. It could offer clues to why people with Alzheimer’s can often recall childhood memories, but not recent ones, as the hippocampus and entorhinal cortex areas of the brain are some of the first to be damaged by the disease.

Wellcome Fellow Dr Caswell Barry from the department of Cell & Developmental Biology at UCL said: “This is the first time we’ve seen coordinated replay between two areas of the brain known to be important for memory, suggesting a filing of memories from one area to another. The hippocampus constantly absorbs information but it seems it can’t store everything so replays the important memories for long-term storage and transfers them to the entorhinal cortex, and possibly on to other areas of the brain, for safe-keeping and easy access.”

A new weapon against Zika

Sanofi Pasteur Dengue NCNDCCBYWolbachia, a naturally occurring bacterium, has been found to be a critical weapon in combatting the spread of Zika virus according to new research published in Cell Host and Microbe.

Insects that are infected with Wolbachia are unable to transmit certain viruses as the bacterium prevents the virus particles replicating within the insect. The bacterium is already known to inhibit the transmission of Dengue virus and was therefore predicted to be effective against the closely-related Zika virus.

Wellcome-funded researchers fed wild mosquitos and Wolbachia-infected mosquitos with blood containing two recently-circulating strains of the Zika virus from South America. The mosquitos infected with Wolbachia had a greatly reduced amount of virus in their saliva compared to the field mosquitos. It is the first published report on the use on Wolbachia against Zika and suggests that the bacterium might be able to block Zika transmission in the field.

Lead scientist Professor Scot O’Neill from Monash University said: “The method we’re using is safe for humans and the environment, and has received widespread international support from governments, regulators and community members. With additional studies testing Zika and Wolbachia also underway in Singapore and Colombia, we’re well positioned to be part of global efforts combining traditional and new approaches to stop the spread of Aedes-borne viral diseases.”

Other Wellcome Trust research news

  • Scientists have developed a new technique to allow embryos to survive and develop in vitro (outside the body) past the implantation stage. Research into this crucial stage of human development has been hindered as it has previously been impossible to carry out studies on embryos past the point at which they would normally implant in the womb. Published in Nature, this technique will allow scientists to culture embryos up to day 13 of development, a day under the UK legal limit.
  • Five new genes associated with breast cancer have been identified by researchers at the Wellcome Trust Sanger Institute, in the largest-ever breast cancer sequencing study to date. As well as the five genes, the analysis of 560 breast cancer genomes also found 13 new mutational signatures that can influence tumour development. The results, published in Nature and Nature Communications reveal more about the highly individual nature of breast cancer genomes and suggest a role for more personalised treatment of these tumours.
  • Antibiotic drug-resistant epidemics could be tackled in real time by combining DNA sequencing and laboratory tests with internet-based location tracking and computer analysis. Researchers developed an on-line tool called Microreact and studied the emergence and transmission of the ‘superbugs’ MRSA (methicillin-resistant Staphylococcus aureus) and MSSA (methicillin-susceptible Staphylococcus aureus) across 450 hospitals in Europe. This research is published in mBio.
  • A new class of drug could offer hope to men with aggressive prostate cancer that has stopped responding to conventional treatment. Wellcome-funded researchers studied a type of drug called Hsp90 inhibitors which target the mechanism that prostate cancer cells use to evade normal treatment methods. This research is published in Cancer Research.

Image credits: RobotEwok via Flickr, CC-BY-NC-ND; SEM of E. coli, Debbie Marshall, Wellcome Images; Human brain cells, Spike Walker, Wellcome Images; Aedes aegypti mosquito, Sanofi Pasteur via Flickr, CC-BY-NC-ND

Image of the Week: The Making of Dawn Chorus

6 May, 2016

 

As part of Wellcome Collection’s new exhibition, THIS IS A VOICE, artist Marcus Coates has been participating in Voicings, a programme of performances and demonstrations taking place each day in the gallery.

His installation in the exhibition, Dawn Chorus, shows people mimicking birdsong while going about their morning routines. Visitors who come to the exhibition this weekend can see people doing this live – although hugely slowed down to allow the bird sounds to be replicated by human voices.

This offers participants the chance to enter the realm of a bird’s song from a unique perspective. Once slowed down, the hidden dynamics and rhythms start to appear. The songs become human in scale and within our reach, asking us to examine our relationship to these strange vocals, how they compare to our own, and what this says about the voice as a form of expression across species.

Dawn Chorus was funded by a Wellcome Trust Arts Award back in 2007, so today’s image is a film about how it was made. You can see Dawn Chorus in THIS IS A VOICE at Wellcome Collection until 31 July 2016.

Credit: The making of Dawn Chorus, 2007, Marcus Coates

Gene therapy restores sight in people with inherited blindness

29 Apr, 2016
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Professor Robert MacLaren carrying out gene therapy at the John Radcliffe Hospital

Researchers at the University of Oxford have found gene therapy can return some sight to people with inherited blindness for up to four years after treatment. 

Scientists used gene therapy to treat people with chorideremia – a genetic disease causing progressive loss of vision, and eventually complete blindness. 

They injected a harmless virus directly into the eye to replace the gene missing in people with chorideremia. Four years after treatment, two of the six people on the trial had much better vision, and three had no deterioration in their treated eyes. 

Professor Robert MacLaren, who led the study, said this seemingly permanent effect “is the breakthrough we have all been waiting for”. 

It’s hoped gene therapy could restore sight in people with other types of inherited blindness, including retinitis pigmentosa, and age-related macular degeneration. 

Wellcome funded the study, published this week in the New England Journal of Medicine, through our Health Innovation Challenge Fund in partnership with NIHR. 

A follow on trial of 30 further patients will now take place.

Read more about the trial results in the Oxford University Hospitals NHS Foundation Trust press release

 

 

 

Image of the Week: The experimental diet that mimics a rare genetic mutation

28 Apr, 2016

mosaic food

This is an excerpt and image taken from the article, ‘The experimental diet that mimics a rare genetic mutation’ by Peter Bowes, published by Mosaic.

A group of people in Ecuador have a form of dwarfism that protects them against some diseases and ageing. Peter Bowes discovers the science behind their condition, and asks whether the health benefits of this particular genetic mutation could be replicated by a diet involving fasting.

Zvi Laron, a researcher working with people of stunted growth, first identified the condition in the late 1950s.

Laron found that his patients had the body’s primary growth hormone (GH) in abundance in their bloodstream, an observation that seemed to defy logic, since they had stunted growth. He concluded that their dwarfism was caused by damage to GH receptors in the liver. It results in extremely low levels of another growth hormone, known as insulin-like growth factor-1 (IGF-1).

In the normal sequence of events, GH, secreted by the pituitary gland, locks on to GH receptors, initiating the production of IGF-1 in the liver. But if a mutation has caused the receptors to be faulty, there are two major effects: the body is unable to generate IGF-1 and the individual is more sensitive to the hormone insulin, which helps regulate the amount of sugar in the bloodstream.

Because IGF-1 stimulates cells to grow and divide, lack of it is linked to a lower risk of cancer – uncontrolled cell division. Meanwhile, a greater sensitivity to insulin helps to prevent diabetes.

There are about 350 “Larons”, people living with Laron syndrome, today, about a third of whom live in Loja, a remote, mountainous province of southern Ecuador. They grow to about a metre in height and experience delayed puberty.

Historians think that Ecuador’s Larons descended from conversos, Sephardi Jews who converted to Christianity and fled to South America at the time of the Spanish inquisition in the 16th century. At first there may have been just one person who had no outward symptoms but passed on a recessive gene. It is assumed that, over generations, inbreeding in the small, isolated Ecuadorian community led to children being born with copies of this gene inherited from both parents – which causes Laron syndrome.

It was Jaime Guevara-Aguirre who in 1988 began studying Larons living in Ecuador. He has been caring for about 100 Laron patients for the past three decades.

During this time, Guevara-Aguirre has had only one Laron patient die of cancer and none from diabetes. This is in contrast to their relatives without Laron syndrome, who have a death rate from cancer of 17 per cent and 5 per cent from diabetes. Despite higher body fat, Larons have a lower resistance to insulin and a much lower incidence of diabetes. And they do not need to fast to achieve this. They eat what they like and are often obese. Because the mutation in their GH receptors blocks the production of IGF-1 in their bodies, they can get fat and still not develop diabetes.

“They’re the human version of what the research of many groups has shown in simple organisms,” says Valter Longo, biogerontologist and director of the University of Southern California Longevity Institute. Longo and others have shown that you can significantly extend the life of yeast, nematode worms, flies and rhesus monkeys by introducing mutations that affect growth. Scientists have also found that mice, when genetically modified so that their GH receptors are impaired, enjoy lives 40 per cent longer than normal. What’s more, their longer lives are also free of major diseases.

“It’s a remarkable increase in health span, in addition to longevity,” says Longo. He believes the same could apply to humans. The ageing process appears to be controlled, in distantly related organisms, by similar genes and mechanisms. “The thing about the Laron dwarfs in Ecuador,” David Gems, Professor of Biogerontology at the Institute of Healthy Ageing, University College London says, “is that they provide some tantalising evidence that this control of ageing extends from the animal models up to humans.”

This is an excerpt taken from the article, ‘The experimental diet that mimics a rare genetic mutation’ by Peter Bowes, published by Mosaic: the magazine dedicated to exploring the science of life, at the Wellcome Trust. Read the full article on mosaicscience.com.

Image credit: Michael Driver

World Immunisation Week: Seven vaccine challenges

25 Apr, 2016

C0105595 Dr Felicity Hartnell. Ebola vaccine trial

The focus of WHO’s World Immunisation Week is closing the immunisation gap, which means getting vaccines that already exist to those who need them. But there are many diseases for which we do not have a vaccine, or the vaccine we have is not effective enough. Here Dr Charlie Weller, who leads the Wellcome Trust’s vaccines work, highlights some of these infections, and why developing a safe and effective vaccine is particularly challenging.

Most of us take vaccines for granted. We are used to getting regular injections when we are children and teenagers, and occasionally when we go abroad.

But, we still lack vaccines to many of the most common infectious diseases, not to mention emerging infections and neglected tropical diseases.

Vaccines work by mimicking our body’s natural response to an infection so that the next time we are exposed, our immune system knows how to respond and protect us against disease.

The steps to developing a vaccine are similar across all diseases, but each comes with its own specific challenges. Here are seven infectious diseases for which vaccine development has proved a tough nut to crack.

HIV

B0005764 HIV particles

HIV hides inside the immune system, infecting the very cells that are needed to coordinate a response against the virus. Many years and billions of dollars have been invested in developing an HIV vaccine. Some hope came in 2009, with a vaccine which protected 31% of people. Researchers are trying to understand what parts of the immune response protected those people, so that they can design better vaccines. In a promising development, researchers have recently found antibodies that completely block HIV from infecting cells and are racing to design vaccines that recreate them.

Malaria

B0006286 Plasmodium falciparum

Unlike diseases caused by viruses or bacteria, malaria is caused by a tiny parasite with a complex life cycle. After more than 25 years in development, at a cost of over $800m, the first malaria vaccine was licensed in 2015. However, the RTS,S vaccine was less effective than many hoped – protecting only around a quarter to a half of children. Still, as malaria is responsible for over 500,000 deaths every year, RTS,S is still a huge breakthrough that could save many lives. We now need to figure out how best to use this new vaccine in combination with bed nets, mosquito control and other approaches.

Rotavirus

Multiple_rotavirus_particlesMore than half a million children under five die each year from rotavirus infections. Most of these happen in developing countries, where getting existing vaccines to those who need them is problematic for many reasons including what’s called the ‘cold chain’.  Vaccines are very sensitive to temperature and must be transported from the manufacturer to the patient in a series of fridges or freezers stretching across the world. In rural areas or those prone to power cuts, up to half of vaccine doses are ‘spoilt’ because the cold chain is broken or faulty. Making existing vaccines more tolerant to heat and freezing would reduce waste and increase access to life-saving vaccines. Work by the Wellcome-funded Hilleman labs in India is underway to achieve this for rotavirus.

Tuberculosis

TB.jpgThe BCG vaccine has been used for over 90 years. It protects against more severe forms of TB, but is not effective against pulmonary TB (in the lungs). One third of the world’s population is estimated to be infected with TB, but not everyone who carries the bacterium will get sick. Finding out why is crucial to designing a more effective vaccine. The need has never been more pressing, with resistance to TB drugs on the rise around the world. People with TB must take daily antibiotics for up to nine months, but many stop taking them earlier contributing to the problem of drug resistance. The situation is so bad that there are now people with TB who cannot be cured.

Chagas disease

598_lores.jpgChagas is caused by a parasite Trypanosoma cruzi that infects humans through the bite of a blood-sucking bug. It is found mainly across Latin America in some of the poorest communities. Like malaria, T cruzi parasites have evolved to hide from the human immune system. One approach is a therapeutic vaccine – given to people already infected to ‘boost’ their immune system to eliminate the parasite once and for all. However, vaccine development is expensive, and for this complicated disease which affects mainly those who can’t pay for a vaccine, the field is lagging behind.

Flu

8411599236_9c1814cbf7_z.jpgFlu is a seasonal illness, and each new season brings with it a slightly different form of the virus. This means a new flu jab must be made each year to match the circulating strains that experts have predicted are most likely to become a problem. A big worry is that it can take six months to make the first doses, so if a flu virus changes and suddenly becomes very deadly (pandemic flu), it might take many months before enough vaccine can be made to protect everyone.

Researchers are trying to create a ‘universal’ flu vaccine, which would provide lifelong protection from all strains of the virus. But this is a long way off. In the meantime, the WHO is helping countries to increase their manufacturing capacity so they are ready to produce as much vaccine as possible in the event of a pandemic.

Zika

20541_lores (1).jpgZika has rarely been out of the headlines since the beginning of 2016. This mosquito-transmitted disease is in the same family as dengue, chikungunya and yellow fever. At the start of the current epidemic in South America, no vaccine candidates existed. However, Zika vaccine development is progressing rapidly, including one approach that uses the dengue vaccine as a ‘backbone’. As the dengue vaccine has already been shown to be safe in people, this approach may speed up development.

An added complication of Zika vaccines is that the people most in need of protection are pregnant women or women thinking of becoming pregnant. These women are usually initially excluded from clinical trials, so we must figure out the safest but quickest way to ensure a vaccine gets to them.

Find out more about Zika research we’re funding.

Image credits: (from top to bottom) Wellcome Images; R. Dourmashkin. Wellcome Images ; Spike Walker, Wellcome Images; Jim Surkamp via Flickr, CC-BY-NC; Wellcome Images; CDC/ Dr. A.J. Sulzer; NIAID via Flickr, CC-BY; CDC/ Cynthia Goldsmith

Image of the Week: St George and the Dragon

22 Apr, 2016

B0010648 St George and the dragon - T lymphocyte killing a cancer cell

With St George’s day on the horizon, our image of the week tells the story through cellular processes found in the human body. The part of St George being played by a T-lymphocyte (blue) and that of the slain dragon by a cancer cell (green).

A killer Image

A T-lymphocyte, or T-cell, is a type of white blood cell. This particular T-cell is the cytotoxic kind (toxic to living cells), and is therefore able to identify dangerous cancer cells and destroy them. Here, the red granules are the T cell’s killing weapon; they are cytotoxic granules and are able to permeate the cancer cell membrane, releasing lymphokines which signal an immune response and activate the process of apoptosis (cell death).

The cancer cell here shows the nucleus (black), the endothelial reticulum (the green parallel bars, middle left) and many internal vacuoles in various colours, representing the self-digesting process associated with apoptosis. The power of the T-cell alone, however, is not always enough to succeed in its task, as it is often difficult to achieve accurate identification of a cancer cell.

It is the potential power of these T-cells that have led research scientists to continue to investigate how they might be manipulated further. It is hoped they will help to provide much safer, and more effective, treatments for cancer, which work in conjunction with the bodies own immune response. This has led many to believe these cells could be our ‘knight in shining armour’ against cancer.

A video showing the ‘warrior’ T-Cell at work can be seen here.

The legend

According to the Christian belief, in the story of the heroic St George, patron saint of England, many people died before the monstrous dragon could first be wounded and then publicly killed. On its death the king established a Christian church in St George’s name, and within it a ‘fountain of living water’ which was said to heal the sick.

More of the story and legend of St George can be found here.

The artist

This image is one of a collection acquired by Wellcome Images from London-based scientific artist Odra Noel. Odra trained as a doctor and has a PhD in basic science from the University of London. Her art training includes a BA in aesthetics and music.

From her exposure through the microscope to cell culture, organ dissection, tissue analysis and morphological studies, she has developed an enthusiastic interest in scientific art. The original artworks are painted silks which have been digitised for inclusion in our image library, Wellcome Images.

To find out how you can use Odra’s images get in touch images@wellcome.ac.uk

 

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