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Image of the Week: Killer T Cells Caught on Camera

22 May, 2015

In this striking video, researchers at the University of Cambridge have captured our body’s ‘serial killers’ – cytoxic T cells which hunt down and destroy tumour cells. Cytoxic T cells are a specialised type of white blood cell whose function is to patrol our bodies and kill cells which are cancerous or infected with viruses.

Shown as orange or green in the video, these specialised cells travel around our body using protrusions to explore the surface of the cells they encounter. If they detect the cell as cancerous or infected (blue), they are able to bind to them and inject poisonous cytotoxin proteins (red) to kill the cell.

To capture these crucial events researchers used high-resolution 3D time-lapse imaging. By taking multiple slices through an object and ‘stitching’ them together they built up a final 3D image of the entire cell.

Wellcome Trust Principal Research Fellow Professor Gillian Griffiths said: “In our bodies, where cells are packed together, it’s essential that the T cell focuses the lethal hit on its target, otherwise it will cause collateral damage to neighbouring, healthy cells. Once the cytotoxins are injected into the cancer cells, its fate is sealed and we can watch as it withers and dies. The T cell then moves on, hungry to find another victim.”

Reference: Ritter, AT et al. Actin depletion initiates events leading to granule secretion at the immunological synapse. Immunity; 19 May 2015

Directors Update: Looking again at Population Health and Clinical Research at the Wellcome Trust

21 May, 2015

Dr Jeremy Farrar, Wellcome TrustIn this post Wellcome Trust Director Jeremy Farrar explains how we are reconsidering our activity in population health and clinical research, and unveils two new senior roles that have been created to reflect this change…

Since joining the Wellcome Trust I have dedicated a lot of my time to listening to our grant holders, understanding the huge range of research that we support, and developing our ‘offer’ beyond funding in terms of our policy, communication and public engagement work.

Two areas that I know are of particular interest to our community, and which we have identified for improvement, are population health and clinical research. Both fields have a long and proud history at the Wellcome Trust – ranging from large longitudinal studies like UK Biobank and ALSPAC, to the very influential National Survey of Sexual Attitudes and Lifestyles (NATSAL), to our longstanding clinical research fellowship schemes.

Today, population health – perhaps because of its success – has become a very broad church of activity. Our portfolio of research includes cohort studies in the UK and overseas, health systems research in Africa and India, surveillance, epidemiology, clinical trials and public health interventions – to name but a few.  At the same time, it’s widely recognised by the medical research community that population health as a field of enquiry is reaching a turning point. Most countries are seeing a changing demographic profile, largely due to an aging population.  Patterns of disease are different, with the huge burden of non-communicable diseases like diabetes spreading to lower and middle income countries at the same time as they confront endemic and emerging infectious diseases and increasing antimicrobial resistance. In turn, these changes have an impact on often fragile health care systems and increase the demands on families and on social care provision.

Adding yet another layer of complexity is the impact of environment on health. It has been obvious for some time that the health of populations and the planet are inextricably linked.  This is an area we started to explore three years ago through our Sustaining Health initiative.

Lastly, it is evident that although public health research is a key part of the puzzle, it alone will not be enough to make a real impact on health. We need to broaden our traditional view of public health to ensure we can address the challenges of the 21st Century and bring a capacity for influencing policy and practice much more to the fore. So, to unite all of this thinking, we are now looking for a Head of Population, Environment and Health who will bring together a new mixed team of research and policy into the Wellcome Trust’s Strategy division to work broadly across the whole organisation.

Clinical research is another crucial part of the Wellcome Trust portfolio.  Alongside the changes outlined to our population, environment and health activity, we are now bringing together clinical research programmes under one team within the Science division, led by a new Head of Clinical Research.

The new role will bring strong leadership to our clinical activity and work closely with medical schools to facilitate cutting-edge research. We are looking for an individual who, similar to my own career, combined clinical medicine and research and will understand the demands of developing a research career alongside medical training, clinical specialisation and a home life.

One of the keys to this will be our new plan for clinical research careers, to be launched later this year, which will significantly increase opportunities for early career clinical researchers aimed to nurture the clinical research leaders of the future.

Our new clinical research lead will also have a huge opportunity to work with others through our large network of collaborators around the world. These include funding partners such as the UK government and funding councils, charities, other global foundations, MSF and other NGOs, and intergovernmental bodies including the World Health Organisation and the World Bank.

What the two new roles have in common is a strong priority to foster collaboration both inside and outside the Trust. Both teams will input their expertise into wider conversations about medical ethics, economics, policy and public engagement. The challenge of funding research that has a dramatic impact on improving human health is that often the most promising solution does not fit easily into one discipline. We envisage that applications for research to both these teams will be strongly interdisciplinary and well suited to our Collaborative Awards.

We welcome inquiries and applications to both the positions outlined here. Visit the Wellcome Trust jobs pages for more information.

Wellcome Trust Research Round-up: 18.05.15

18 May, 2015

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

Two new targets for cancer treatment

B0004178 Illustration of a cell in telophaseTwo studies published in the Journal of Cell Biology have identified potential new targets for the treatment of a wide range of cancers.

The research looks at advancing our understanding of cell division in normal cells, how this goes wrong in cancer, and how this may be targeted in a cancer-specific way.

Wellcome Trust-funded researchers found a role for two enzymes, Nek5 and Nek6, in the regulation of cell division. Nek5 functions to ensure an essential structure of cell division, the ‘scaffold’ upon which genetic material is separated, forms at the correct time. Nek6 is then able to recruit ‘chaperone proteins’ to this scaffold to ensure proteins are folded correctly. These chaperones also help to protect the cells from environmental stresses.

The enzymes are attractive targets for anti-cancer therapies – inhibiting chaperone proteins or preventing the scaffold from assembling correctly will disrupt cell division.

Professor Andrew Fry, from the University of Leicester, said: “Together, these two papers provide exciting new insights on how cells ensure that they faithfully pass on the right amount of genetic material to their offspring when they divide. They also highlight potential new targets for the development of novel cancer treatments.”

You can read the two papers here: (1) (2)

Targeting the root cause of asthma

C0015484 Asthma InhalerA potential new target for asthma therapy has been identified by researchers at the Wellcome Trust Sanger Institute.

A specialised type of immune cell, the innate lymphoid cell 2 (ILC2), is involved in the regeneration of lung tissue following damage caused by diseases such as influenza. However, if your body produces too many of these cells it can cause inflammation and, subsequently, asthma.

Researchers have found that the activity of a gene called BCL11B is required to mature newly-produced ILC2 cells and also regulates the number of these mature cells in your body.

Ensuring the levels of these ICL2 cells are high enough to help prevent influenza infection, but not so high that they can cause asthma is essential. Therefore researchers are hopeful that the manipulation of the activity of this BCL11B gene could offer a potential for target for therapy.

“Before now, asthma treatment has focussed on treating symptoms,” says Professor Gordon Dougan, a senior author and group leader at the Wellcome Trust Sanger Institute. “Now that we have joined the dots between the development of ILC2 cells and the expression of BCL11B, we can begin looking for drug targets that will tackle asthma’s root cause.”

This research is published in the Journal of Experimental Medicine.

Immune response silenced by Hepatitis B virus

B0009950 Hepatitis B virus (HBV) particle, illustrationThe body’s immune cells are left starved of essential nutrients by Hepatitis B infection, leaving them unable to control the disease, a new Wellcome Trust-funded study has found.

Although the adult immune system is usually able to control acute hepatitis B infection within a year, chronic infection lasts throughout life and causes liver damage and cancer. By controlling suppressor cells in the liver the virus can silence immune responses by starving cells of their essential ‘food source’.

Current hepatitis treatments are rarely effective at clearing the disease and although a vaccine does exist, it does not work after infection. Researchers are therefore hoping that by understanding the mechanism by which the virus is able to control the immune system, they may be one step closer to finding a suitable therapy.

Wellcome Trust Senior Investigator Professor Mala Maini said: “If we could boost the immune system and counteract the liver’s suppressive effect, then the infection could potentially be cleared after a large ‘burst’ of immune activity. This might cause short-term damage to the liver, but would prevent the long-term damage from scarring and liver cancers that we see in chronic patients.”

The research, published in Nature Medicine, may also offer an insight into controlling harmful immune responses following organ transplantation.

Spread of drug resistant typhoid

5279772517_d5b81fba0e_zThe global spread of antibiotic resistant typhoid is driven by a single family of typhoid bacteria, according to a new large scale genomics study.

In research led by the Wellcome Trust Sanger Institute, scientists collected data from more than 24 countries to create one of the most comprehensive data sets for a single infectious agent.

This data is an essential step in developing global surveillance of this public health threat. The results showed that this new family of bacteria, H58 Typhi, is displacing other typhoid strains and subsequently completely altering the genetic landscape of the disease.

Resistant to most front line drugs, H58 Typhi is continuing to evolve and acquire mutations as it spreads. These new mutated genes, which give the typhoid bacteria their resistance to new antibiotics, are becoming stable parts of the H58 genome and therefore creating a multi-drug resistant pathogen.

“H58 is an example of an emerging multiple drug resistant pathogen which is rapidly spreading around the world,” says Professor Gordon Dougan, senior author from the Sanger Institute. “In this study we have been able to provide a framework for future surveillance of this bacterium, which will enable us to understand how antimicrobial resistance emerges and spreads intercontinentally, with the aim to facilitate prevention and control of typhoid through the use of effective antimicrobials, introduction of vaccines, and water and sanitation programmes.”

This study is published in Nature Genetics.

Other Wellcome Trust-funded research news

Researchers have identified a crucial pathway involved in the suppression of immune attacks on our own tissues. The study, published in Immunity, highlights the role of regulatory T cells in preventing damage and suggests that this pathway could be targeted to promote suppression of inflammation in human diseases such as inflammatory bowel disease

In other news…

Congratulations to Professor Lalita Ramakrishnan who has been elected to the US National Academy of Science. A Wellcome Trust Principal Research Fellow, Lalita works on the pathogenesis of tuberculosis and identifying potential therapeutic targets.

The Royal Society and the Academy of Medical Sciences have recently elected their newest Fellows and 19 members of the Wellcome Trust community have been honoured.  Those elected work across the breadth of the biomedical sciences and the Fellowships recognise their contribution to society through the advancement of research. You can see the full list of new Fellows on the Royal Society and Academy of Medical Sciences website.

Image credits: (from top to bottom) Illustration of cell in telophase, Benedict Campbell, Wellcome Images; Asthma inhaler, Wellcome Library; Hepatitis B virus particle illustration, Pete Jeffs, Wellcome Images; Typhoid bacteria by Sanofi Pasteur via Flickr, CC-BY-NC-ND

Surgical equipment sent to Patan Hospital, Nepal

15 May, 2015

The surgical euipments doanted by OUCRU-Vietnam

The Wellcome Trust has sent surgical equipment to Patan Hospital in Kathmandu, Nepal to contribute to the on-going response to the earthquakes in the region.

The 450-bed hospital is also the base for the Oxford University Clinical Research Unit (OUCRU-Nepal) and received hundreds of patients in the immediate aftermath of the earthquakes. Many of these patients had severe orthopedic injuries and some were helicoptered in from remote villages.

Setting up Field Hospital OT

Despite the hospital building withstanding the quake well, the doctors and nurses are in vital need of more equipment to be able to continue effectively treating the large number of injured patients. Via the Oxford University Clinical Research Unit in Vietnam, the Wellcome Trust has donated a laparoscopic machine, bronchoscope system and a diagnostic ultrasound system.

The images here have been sent by Dr Guy Thwaites, Director of OUCRU-Vietnam and show the equipment in arriving and in action at the hospital.

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You can read Dr Buddha Basnyat’s personal account of the earthquakes striking Nepal here

Image of the Week: Day 489, Perfect Focus

15 May, 2015

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In recognition of Mental Health Awareness Week (11-17 May) our image of the week is Day 489, Perfect Focus from Bobby Baker’s Diary Drawings: Mental Illness and Me. This is one in a series of more than 700 drawings by the acclaimed artist and performer Bobby Baker that chronicle her journey through mental illness.

“In 1997 I had the first of many ‘breakdowns’ and received a psychiatric diagnosis. Like many people entering the mental health system I collected other diagnoses over the following 11 years. I’ve discovered that it’s rather hard to fit human beings into systems, as we are all unique. I was fortunate that my extensive track record as an artist and the skills I had learnt, proved to be a great asset – a valuable method for self-reflection and an effective and tool for communicating with others.

During those 11 years I kept a weekly diary of drawings. In 2009 we curated a selection of them into an exhibition at the Wellcome Collection, Bobby Baker’s Diary Drawings: Mental Illness And Me 1997-2008. The exhibition generated a remarkable level of public and critical acclaim. The accompanying book of the same name was awarded MIND Book of the Year in 2011. A national and international touring programme of large, small and digital versions of the exhibition is ongoing.

I’m proud to describe myself as an ‘expert by experience’ of the mental health system, and ultimately of my own mental health. I now know what makes my life so richly worth living now. What I finally realised was that it’s not me that is mad – but the world!

Along the way I’ve met the greatest people, who also describe themselves as experts by experience. Mental illness is commonly seen as a deficit and weakness. I want to show otherwise that we have much to contribute and teach, and that society can learn from us.

I’m the Artistic Director of Daily Life Ltd. We’re a small arts and mental health organization based in East London. Our mission is to create powerful art that changes the way people think about mental health.

We believe that art can provoke a ‘way of looking’ rather than just providing material to look at. It is wise to never underestimate the extraordinary capacity we all have through the creative arts for illumination.”

Bobby Baker

Follow Bobby Baker on Twitter or visit Daily Life Ltd’s website for more information. 

Image credit: Day 489, Perfect Focus from Bobby Baker’s Diary Drawings: Mental Illness and Me, 1998 – 2007; Watercolour paper, pencil, watercolour; Drawing © Bobby Baker, Photograph © Andrew Whittuck

Primary priority: how supporting teachers makes science exciting

13 May, 2015

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How old were you when you got interested in science? Wellcome Trust primary science lead, Louise Stubberfield, dreams of a world where children are excited about science and discovery from a young age. She tells us how the Trust is taking action to make that world a reality.

We know that children start to develop perceptions about science toward the end of primary school (Aspires survey from Kings College London). We also know that they carry these perceptions with them throughout their school career, affecting their performance and later interest. So, excellent and engaging primary science teaching is an essential step on the path to a lifelong interest in science, making a difference not only to individual futures, but for all of us through breakthroughs in research or innovation in engineering.

Last year, we launched a report of primary science teaching in the UK – Primary Science: is it missing out? The answer is ‘yes’, for the most part, it is. Many primary teachers lack confidence to teach science well, and primary science leaders often have little experience of science beyond their own GCSE lessons – they manage science in schools rather than leading it. The report made recommendations about ensuring appropriate scientific expertise in schools, and highlighted the importance of a system that values science beyond exams and attainment outcomes.

15276285611_a2c3bd7a3b_kThe good news is that this is a very achievable goal. Working with the National Science Learning Centre, we have developed an intensive programme of continuing professional development (CPD) to give qualified teachers new and improved skills for teaching and leading science in their primary schools. We also commissioned a randomised control trial to evaluate it, with the data showing how pupils’ attitudes and achievement improved when taught by teachers with increased expertise.

“I’m more confident to help colleagues in school, answer their questions, whereas before I wouldn’t have been able to answer their questions, and now I can have a clear grip on what’s going on in school, talk about misconceptions, and as a result our school has moved forwards immensely in science.” (Trial participant)

Conducting a randomised control trial over two years is very hard to do, with so many different factors at play in the various school environments. However, it was clear that just raising the profile of science in a school, by taking part in the trial, might prove to be very beneficial. Similarly, having school leaders that signed up to the commitment and made sure that participating teachers could do what they needed to do to improve their school’s science, made a positive difference too.

FP0000142F02 Child, at secondary school Credit: Fiona Pragoff /. Wellcome Images images@wellcome.ac.uk http://images.wellcome.ac.uk Child, at secondary school looking through a magnifying glass. Photograph Published:  -  Copyrighted work available under Creative Commons by-nc-nd 2.0 UK, see http://images.wellcome.ac.uk/indexplus/page/Prices.html

The trial has also enabled the National Science Learning Centre to evaluate and refine the CPD course, which has now been taken by over 160 teachers. One teacher on the refined course commented that ‘achievement has increased and science has become a focal point of celebration throughout the school. We have been used as a model of good practice for teaching students [student teachers] specialising in science.’ We couldn’t ask for a more promising outcome.

We can continue to make recommendations about improving primary science or, we can make sure it happens. At a workshop we held recently here at the Wellcome Trust, representatives from across the science education sector agreed to do just that, starting with  getting the message out to all education leaders that primary science matters; that aspiring primary science leaders should be able to access the CPD they need, and that it should be a priority. When primary science is valued, children’s perceptions of the subject can be changed, even if they have struggled or thought ‘science is not for me’. No longer something dull or difficult, science becomes exciting, and that is exciting for us!

Primary Science is a key priority for the Wellcome Trust. Find out more about our primary science projects and check out an example of how one primary school is transforming science lessons with a dedicated lab and scientist-in-residence.

Image credits: (from top to bottom) woodleywonderworks via Flickr, CC-BY; Laurie Sullivan via Flickr, CC-BY; Wellcome Images

Researcher Spotlight: Dr Rebeccah Slater

11 May, 2015

RSDr Rebeccah Slater is a Research Career Development Fellow based at the University of Oxford. Her research focuses on understanding infants’ experience of pain using brain-imaging and how we can improve pain management. Here she tells us more about her lifelong interest in child development…

What are you working on?

I’m interested in how the human brain develops during early infancy. I’m developing an understanding of how the immature brain responds when infants are first exposed to tissue injury and begin to experience pain. My research group uses non-invasive brain imaging tools, including EEG and fMRI, to explore the development of the human nervous system. At the moment I am using fMRI to demonstrate that newborn infants have the sensory and emotional capacity to experience pain in a similar way to adults. I am about to use novel brain-imaging methods in a clinical trial to investigate whether morphine analgesia can provide effective pain relief for infants.

What does your average day involve?

I am in a very exciting phase of my career and it is a privilege to be able to exclusively focus on research. I am currently building a new young research team so most of my time is spent guiding

and motivating students, post docs and clinical researchers. On a day-to-day level this involves discussing and interpreting new data, writing manuscripts and grants and coming up with lots of new ideas for the future. In practice, I spend a lot of my time talking to my research team and colleagues about how we would like to shape our research direction.

Why is your work important?

Rebeccah's research team

Rebeccah’s research team

Historically, there has been a predisposition to undertreat pain in babies. In part, this has arisen because it is difficult to measure infant pain. As babies can’t tell us when they are in pain, it can be hard to assess whether pain medication is working. A recent study showed that while babies in intensive care experience an average of 11 painful procedures per day in the first 2 weeks of life, less than 40% received any pain relief. We need better ways to measure infant pain if we want to develop more effective treatments. My colleagues and I have shown that when painful procedures are performed in infants, the nervous system transmits this information to the brain, nevertheless little is known about which parts of the brain are involved in the infant pain experience or how this information is interpreted. This is an area of research in which I am currently involved (Goksan et al., eLife). If we can identify the parts of the brain that are active when infants experience pain, this may help us to infer some understanding about how infants interpret the experience.

 

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

Ultimately I would like to improve the treatment of pain in babies. By developing new ways to measure infant pain, we may be able to provide better treatment. I would hope that this would reduce some of the long-term behavioral and cognitive consequences that are associated with exposure to pain in early life.

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

From a very young age I was interested in how children develop – when I was young I thought I wanted to work in a nursery school and chose to do a GCSE in Child Development. My first degree was in Physics and I quickly became interested in the biophysics of nerve cells. I knew I wanted to do a Neuroscience PhD but I didn’t think I had enough basic grounding, so decided to do a Neuroscience Masters at UCL. At this time I worked at The Institute of Child Health. My physics background and curiosity about child development meant I developed an interest in brain imaging in children. During my PhD I made the first observations that the newborn infant brain was activated following painful procedures, and since then have continued to use brain-imaging techniques to help us improve our understanding of infant pain.

Baby Amy in MRI Scanner

Baby Amy in MRI Scanner

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

The Wellcome Trust Funding has been incredible. It has given me the opportunity to pursue my own research ideas and set up my own research group with a fabulous team of people. It has ensured that my time is protected so that I can fully concentrate on research. The personal interactions with Trust staff have also been extremely rewarding and helped shape the focus of my research. I am privileged to be a Wellcome Trust Fellow. It has opened up many opportunities for me, and directly resulted in Oxford underwriting my Fellowship with a full academic position.

What’s the most frequently asked question about your work?

I am often asked why it is not simply obvious that babies feel pain. People can see that babies cry and grimace when they have painful procedures like vaccinations or blood tests, so they are intrigued about why pain is difficult to measure. The answer to this lies in the fact that behavioral responses are not necessarily well correlated with the experience of pain – especially in the immature developing nervous system.

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

I don’t dread any questions about my work. I love talking to people about what I do. When talking to wider audiences the breadth of questions always surprises me.

Tell us something about you that might surprise us…

My brother and sister are both musicians and I learnt very quickly that I didn’t share their musical talents. However, during my University days I established and managed a small chamber orchestra called the Covent Garden String Consort. This Chamber group still exists and regularly performs classical concerts in the UK and abroad.

What keeps you awake at night?

My son – I optimistically lie in bed hoping that he won’t wake up – this rarely ever happens.

What’s the best piece of advice you’ve been given?

“If you focus on doing high quality science everything else will work out” Irene Tracey

The chain-reaction question, posted by previous spotlightee Professor Lora Heisler is this: What do you predict to be the biggest medical scientific discovery/achievement of the 21st century?

Understanding the workings of the human brain and applying this knowledge to improve our understanding of mental health.

To find out more about Rebeccah Slater and her research you can visit the University of Oxford website.

Image credits: Provided by author

Image of the Week: the world’s largest cyanotype

8 May, 2015

This week’s Image of the Week shows a section of the world’s largest cyanotype, created by artists Melanie King, Constanza Isaza Martinez and Andres Pantoja. It measures 7 x 14 metres and over 20 volunteers helped create the bold blue pattern, setting a new Guinness World Record. The previous world record was set by Melanie King at the Story of Light Festival in Goa, India in January 2015. This one was created on a slighty gloomy afternoon in London as part of a weekend of activity called On Light.

The cyanotype process is a simple method of photographic printing, invented in the 1800s. It uses a photosensitive solution to create a cyan-blue print and was often used by engineers as a cheap and easy way to reproduce diagrams, or ‘blueprints’.

To make a cyanotype a white canvas is coated with a mild photosensitive solution containing ammonium citrate and potassium ferricyanide, turning it pale green. When exposed to UV light from the sun the compounds in the solution react to form an insoluble blue compound, ferric ferrocyanide, also known as Prussian blue, changing the colour of the canvas to blue. If something, or in this case someone, blocks the sunlight from hitting the canvas, the canvas remains the original shade of green. Once the print has developed the unreacted green solution is washed out of the canvas, leaving behind the bright white shapes on a deep blue background that you can see in the image above.

For Saturday’s record attempt Melanie and her team invited members of the public to lie sprawled across the canvas while it developed, each person striking their own distinctive pose (I’m the one on the bottom left!). In the centre of the canvas they placed a selection of circular objects, to make a streak of circles across the centre of the print, like a band of stars. We had to act quickly, as once the canvas was unrolled the solution immediately started to react. Getting everyone on and off the canvas swiftly was essential to creating crisp, clear shapes. So too, was lying still for the 20 minutes it took for the print to develop – with more than 20 people taking part it’s remarkable that we managed it!

Congratulations to Melanie King, Constanza Isaza Martinez and Andres Pantoja on their new record.

On Light was a four day programme of events held by Wellcome Collection in partnership with UCL to mark the International Year of Light and Light based Technologies. For more information about Wellcome Collection events, visit the Wellcome Collection website.

When the earth shook: a view from Patan Hospital in Kathmandu

6 May, 2015

On 25 April 2015 a 7.8 magnitude earthquake shook Nepal. Centered in the village of Barpak in the Gorkha district of the country,  it is the most powerful quake to hit the country since 1934. So far it is estimated that over 7000 people have died, with hundreds of thousands more made homeless. Buddha Basnyat is the Director of the Oxford University Clinical Research Unit in Nepal, which is supported by the Wellcome Trust. Here, he tells us about his experience of the earthquake and the on-going effort to help people affected…

 

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When the first tremor shook Kathmandu at midday, Saturday April 25, I was working at my desk peer reviewing an article about high altitude medicine. I thought this was a mild quake, another one of those earthquakes not uncommon in Kathmandu. It was only when I was going down the stairs (absolutely the wrong thing to do) and swaying like a drunk, I realized this was no ordinary quake (7.8 magnitude) and I could die sandwiched in my own concrete staircase. I flung the house door open and ran to the gate and prayed like a man possessed.

Most of the Nepalis that survived the quake experienced this immediate feeling of desperation. We had aftershocks that day, but when the second strong aftershock (6.8 magnitude) hit the next day, it felt like we were in the relentless grasp of a demon. It was only a few days later when we had our wits (or at least some) about us we realized that in all likelihood we would not have another major quake so soon in the Himalayas. The strength of the aftershocks would keep on decaying and level off.

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At Patan Hospital, where there are 450 beds, and where the Oxford University Clinical Research Unit (OUCRU-Nepal) is based, the many disaster/earthquake drills and the retrofitting of the hospital building that had been patiently carried out by the hospital authorities over time paid rich dividends. In general the hospital building has withstood the quake – unlike many other hospitals in the valley.

In the immediate aftermath of the earthquake hundreds of patients with severe orthopedic injuries including many open fractures flocked to Patan Hospital from all over the country. Many were helicoptered in from remote villages.  Dr Nabees Man Singh Pradhan and his team of orthopedic surgeons started operating on these patients almost non-stop using the many locally available implants, external stabilizers and other forms of orthotics. Clearly these surgical procedures, which were carried out promptly by these Nepali doctors at Patan Hospital, will be one of the most unforgettable things the hospital has done since it opened its door as Shanta Bhawan Hospital in 1956.

Dr Guy Thwaites who is the head of the OUCRU-Vietnam, with whom OUCRU-Nepal has been  closely aligned for about 12 years,  phoned me immediately after the quake to check on the safety of the staff. I was glad to report to him later that our OUCRU staff had escaped unscathed except for severe damage to property for three of us. Dr Jeremy Farrar, who Dr Thwaites replaced, also promptly checked on our safety. In fact post- earthquake Nepal has received a phenomenal amount of goodwill and help.

Immediately after the quake Dr Amit Arjyal and Mr Rajendra from OUCRU-Nepal, together with doctors from Patan Hopsital went to some of the worst hit districts, Sindhupalchok and Nuwakot. There, they distributed  food, tents and medicines with money they had raised. They brought back many images including those of water shortages and children drinking water from a dirty pool.

Our work at the Patan Academy of Health Sciences (PAHS, which governs Patan Hospital) will soon focus on the imminent monsoon season and the subsequent onslaught of infectious diseases, which may possibly be made worse by poor sanitary conditions triggered by the earthquake.

17313902285_262f44b067_zOUCRU-Nepal, working closely with PAHS and OUCRU-Vietnam, are considering setting up targeted, rapid (non-culture based) surveillance for enteric infections in the Patan area and in various settlement camps around the city. This would provide real-time data for clinical management and may also help inform vaccination programme responses against infectious diseases like cholera, typhoid and hepatitis E.

All these programmes would be run in collaboration with the Nepal Health Research Council, the government body responsible for coordinating the healthcare response to the earthquake. We would also work closely with the Nepal Public Health Foundation, including working to help people outside the valley in remote areas of Nepal.

Clearly the unfolding saga of this great earthquake (“maha bhukampa” in Nepali), will have a multitude of surprises for us, perhaps beyond our imagination right now. But at the time of writing this it is heart-warming to see the Nepali people come together  with almost palpable optimism. It is as though from this very tragic event, there will be a re-birth and reinvigoration of the nation which will enable people to deal with this tragedy and move, if I may dare say, confidently ahead.

Buddha Basnyat is the Director of the Oxford University Clinical Research Unit in Nepal and President of the International Society of Mountain Medicine. If you would like to find out more about OUCRU-Nepal, please visit their website

Image credits: (from top to bottom) Nepal Earthquake by Domenico via Flickr, CC-BY-ND; Buddha Basnyat; Search and Rescue teams reach Chautara, Nepal by DFID via Flickr, CC-BY

Wellcome Trust Research Round-up: 04.05.15

4 May, 2015

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

A kick in the teeth for HIV

Scientists have found that the human immune system may be capable of handling high bursts of HIV activity – much more than previously thought. This new Wellcome-funded research, published in Clinical Infectious Diseases, has highlighted the possibility of a ‘kick and kill’ cure for HIV.

The technique would use a vaccine to stimulate the immune system, then a chemical ‘kick’. This kick would be capable of awakening all dormant HIV that hides in a patient’s white blood cells, allowing the heightened immune system to identify and kill the virus.

This discovery came to light in a single patient study of a man who was described as an ‘elite controller.’ This means his immune system can successfully control HIV for extended periods of time. Although cautious about the results from just a single patient, scientists are confident that the demonstration of our immune system’s ability to control HIV will help them to further research a cure.

Wellcome Trust Clinical Fellow Dr Ravi Gupta said: “We’re still a long way from being able to cure HIV patients, as we still need to develop and test effective vaccines, but this study takes us one step closer by showing us what type of immune responses an effective vaccine should induce.”

Getting from A to B

L0034555 A map of the world c. 1600Taking a different route to work may help your brain connect smaller, local maps into one global map to help you to better navigate your environment.

Wellcome Trust-funded scientists have found that grid cells, a specialised type of neuron that allows us to understand our position within a certain space, are capable of forming large scale maps of distinct areas.

Scientists measured the activity of these grid cells in the brains of rats that were moving between two identical compartments connected by a corridor. Initially, the activity pattern showed two identical but separate local maps. Over time these maps became different and merged to create a single global map, showing that the rats had learnt how the compartments were linked and their locations relative to each other.

Sir Henry Dale Fellow Dr Caswell Barry said: “Grid cells tell us how far we’ve walked and in what direction, this information can be used by place cells to populate our mental maps. If the maps remain separate then it is not possible to relate the places they contain. Our results show that as we move between the areas, grid cells link everything up.”

This study was published in Current Biology.

A new path to a treatment?

B0003857 Alzheimers' disease - plaque in the brainTwo key proteins involved in the onset and progression of Alzheimer’s disease have been found to be linked in a pathway that could offer a new therapeutic target.

Scientists have found that the breakdown of a certain protein called amyloid precursor (APP) is able to affect the levels of another protein in the brain, tau. The combination of tau and the toxic products of APP breakdown are known to cause plagues and tangles in the brain which eventually lead to neuron death.

Using human stem cells directed to become neurons with all the characteristics of Alzheimer’s disease, scientists were able to test drugs that could slow the breakdown of APP. The saw that by reducing the breakdown of APP, levels of tau were also reduced.

Not only does this research point to a new possible target for Alzheimer’s treatment, it also highlights the growing importance of human stem cells in medical research: “The question is why hasn’t this pathway been identified, given that Alzheimer’s is so well-studied?” said Dr Rick Livesey of the Wellcome Trust/Cancer Research Gurdon Institute. “The answer is that mice don’t develop Alzheimer’s disease, and they don’t respond to these drugs the way human neurons do. It’s something we can only do by looking at real human neurons.”

This research was published in Cell Reports

Other Wellcome Trust-funded Research News

Research published in Lancet Psychiatry has found that the death rate from alcohol and drug misuse in former prisoners is remarkably high. Of prisoners who died within five years of release, around a third of the male deaths and half of the female deaths could be attributed to alcohol and substance abuse. Carried out in Sweden, the study highlights the possible benefit of preventive programmes in reducing the number of deaths.

A new sequencing technique developed at the Wellcome Trust Sanger Institute will be able to sequence the unique genome of an individual cell as well as the pattern of gene activity within it. This unprecedented level of detail will allow scientists to see exactly when mutational damage and other DNA changes occur. This research, published in Nature Methods, hopes to increase our understanding of normal and disease development.

A new study from the Sanger Institute has found that the public are increasingly more curious about the information that is held by their genes. In a survey of nearly 7000 people, 98% of those asked wanted to be informed if research using their genetic data found indicators of a serious preventable or treatable disease.

In other news…

The Wellcome Trust has recently announced funding for Theraclone Sciences’ I-STAR technology, which is able to rapidly screen antibodies from Ebola survivors for high biological activity. It is hoped that the identification of these could lead to the development of a therapeutic antibody.

Researchers at Imperial College London have announced that they are working to develop drugs that could lessen the damage caused by a heart attack, following the receipt of a Wellcome Trust grant. The Seeding Drug Discovery Initiative will support research to identify a potential drug target in the heart and candidate molecules that could help to prevent the death of heart muscle cells.

Image credits: (from top to bottom) HIV-infected cell by AJC, via Flickr CC-SA; Map of the World, Wellcome Images; Alzheimers’ disease – plaque in the brain, Cardiff University & Wellcome Images

Marion Coutts wins Wellcome Book Prize 2015

30 Apr, 2015

coutts3

Last night in the packed out Wellcome Collection Reading Room, Marion Coutts was revealed as the winner of the 2015 Wellcome Book Prize for her book The Iceberg.

Coutts’ memoir of the 18 months leading up to her partner’s death of a brain tumour was described by Chair of Judges Bill Bryson as “beautifully written, painful to read but very, very beautifully expressed. She recalls things with such vivid detail you feel almost as if you are reliving this experience with her. It’s an incredibly powerful book.”

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Coutts was joined by her fellow shortlisted authors before the big reveal: Henry Marsh for his account of his life as a brain surgeon in Do No Harm, Sarah Moss for Bodies of Light about the first female doctors, Alice Roberts for The Incredible Unlikeliness of Being which chronicles our complex evolution, Scott Stossel for his account of one man’s battle with anxiety in My Age of Anxiety and Miriam Toews for All My Puny Sorrows a story of sisters and suicide.

The crowd cheered as Coutts was announced as the winner, clearly agreeing with the decision of the judging panel.

On taking to the stage to accept her prize from Bill Bryson, Coutts gave a heartfelt speech about the inspiration behind the book and dedicated it to her son Eugene and her husband Tom.

Bryson explained the process behind selecting a winner with his fellow judges: “From an extremely strong shortlist of books that blend exquisite writing with scientific rigour and personal experience, ‘The Iceberg’ stood out. Marion Coutts’ account of living with her husband’s illness and death is wise, moving and beautifully constructed. Reading it, you have the sense of something truly unique being brought into the world – it stays with you a long time after.”

The judging panel was chaired by Bryson who was joined by pioneering autism researcher Professor Uta Frith DBE, bestselling author Mark Haddon, BBC presenter Razia Iqbal and barrister Baroness Helena Kennedy QC.

authors

Marion Coutts is an artist and writer. She wrote the introduction to Tom Lubbock’s memoir Until Further Notice, I Am Alive, published by Granta in 2012. She is a Lecturer in Fine Art at Goldsmiths College and lives in London with her son.

To find out more about the prize you can follow Wellcome Book Prize on Twitter or visit the website.

Researcher Spotlight: Professor Lora Heisler

27 Apr, 2015

Heisler lab picProfessor Lora Heisler is a Wellcome Trust Senior Research Fellow based at the Rowett Institute of Nutrition and Health at the University of Aberdeen. Her research looks at the mechanisms underlying the development of obesity and diabetes in a effort to identify new therapeutic interventions. Here she talks about her desire to reverse the obesity epidemic through understanding the brain and meeting Ronnie Wood at the White House…

What are you working on?

I investigate the brain circuits that regulate appetite, body weight and glucose homeostasis.  One of the fascinating aspects of this work is that the brain is still predominantly unchartered territory.  Like early explorers, neuroanatomists have been mapping the brain, compiling their findings in an atlas, and discovering the function of discrete brain regions and the connectivity between them.  It is thrilling to contribute to this body of work – to be the first to discover a functionally defined brain circuit.

What does your average day involve?

Figure 2 -oxytocin hypothalamic expression

Oxytocin “the love hormone” is expressed in the shape of a heart in the hypothalamus

Research is exciting because every day is different.  Usually I start with a basic outline of what I would like to accomplish in a day, but how the day unfolds is often very different.  I typically have a mixture of academic work, university meetings and meetings with my team to plan projects and discuss new experimental data.  This last part is the most exciting. It’s fascinating to make new discoveries about how the brain works to influence how we behave, what and when we eat, especially if we don’t get the answers we expect. I love the way that research is full of surprises!

Why is your work important?

Obesity is arguably one of THE global health care challenges of the 21st century.  Overweight and obesity are incredibly prevalent, with more than half the nation meeting these criteria.  Unfortunately, just like too little body weight, too much is also detrimental to health.  It is not clear why this is case, but excess adiposity (body fat) in obesity is associated with serious illnesses, such as cancer and heart disease, which reduce lifespan and have a detrimental impact quality of life.

Excess body weight is a result of consuming more calories than the body requires.  This excess energy is stored, primarily as fat.  The brain, receiving signals from the gut and body, is the master coordinator of hunger and fullness.  What we are attempting to discern is how the brain integrates this information and how we can interrogate these circuits to prevent and treat obesity.

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

My overall aspiration is to contribute to human health by identifying a means to reverse the obesity epidemic.

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

Since I was a child, I have been curious about the brain and how it regulates behaviour.  While I was at university, my “after school job” was working as a Mental Health Worker on a locked inpatient psychiatric ward, primarily working with patients suffering from major depression and schizophrenia who were treatment resistant.  This work with patients gave me an enormous drive to understand how our brain chemistry and architecture underpins behaviour.  I was particularly interested in the neurotransmitter serotonin or 5-HT and my PhD research was focused on investigating whether the depression and anxiety medication Prozac could be repurposed for obesity treatment.

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

The Wellcome Trust Senior Fellowship has been crucial to my research and career.  I feel very fortunate to have been funded by the Trust for the past 7 years.  Wellcome have provided me with the means to pursue my passion, to recruit a team of outstanding scientists, to capitalise on the latest technology and to break new ground in obesity and type 2 diabetes research.  With my team of excellent post doctoral fellows, we have begun to decipher the neural underpinnings of 5-HT obesity medications and have identified new players in appetitive and gluco-regulatory circuits.

What’s the most frequently asked question about your work?

Why are so many people obese and why is obesity so resistant to drug treatment?

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

I am very curious about the questions people have. What is the primary riddle in their minds related to my work and/or my field?  This interest holds true for my scientific colleagues and the general public alike.  I find the questions both fascinating and illuminating.

Tell us something about you that might surprise us…

Image courtesy of Ray Krebs on Flickr - CC-NC-ND

Image courtesy of Ray Krebs on Flickr – CC-NC-ND

As an undergraduate, I was selected for a competitive internship in Washington D.C. to learn about the inner workings of the government.  I was there for the inauguration of President Bush and attended both the inauguration ceremony (swearing-in in front of the Capital building) and an inaugural ball.  A highlight for me at the ball was seeing the President in person and rubbing shoulders with politicians, celebrities and musicians, including Ronnie Wood of the Rolling Stones. It was a very exciting day.

What keeps you awake at night?

Occasionally, it is difficult to hit the “pause” button on the brain, and on these occasions, I lay awake puzzling over data, circuitry and new approaches.

What’s the best piece of advice you’ve been given?

My undergraduate supervisor Dr. Michael Lyons told me that we spend so much of our lives working, it is a gift to do what you love.  He advised me to always actively pursue what I am passionate about.

The chain-reaction question, posted by previous spotlightee Dr Thomas Ezard is this: What’s the most important tool for successful interdisciplinary research?

Communication.

To find out more about Lora Heisler and her research you can follow her on Twitter or and visit her profile on the University of Aberdeen website

Image credits: Provided by author; Provided by author; Capital Building image by Ray Krebs on Flickr, CC-NC-ND.

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