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Director’s Update: Changes to the Wellcome Trust’s structure and leadership

1 Oct, 2014

Dr Jeremy Farrar, Wellcome TrustSince he joined us this time last year, Jeremy Farrar, Director of the Wellcome Trust, has been listening – to staff, to researchers, to members of the Wellcome community, and more. In this post he explains some changes to our organisational structure and leadership team…

A year ago today, I became Director of the Wellcome Trust. It has been a fantastic twelve months and a wonderful journey, in the course of which I have been listening to people’s views about this great organisation, and learning much about it, from within and from outside. I am very grateful to everyone who has come to talk to me, to share your ideas, your work and your thoughts for the future.

New leadership is always an opportunity to look afresh at an organisation’s direction and structure, and it has been my priority over the past year to think over how best to take forward our vision, together with colleagues from across the Trust and the Board of Governors. In July, I announced an evolution of our funding framework, with a focus on broadening our funding opportunities for younger researchers, for teams, for people with innovative ideas and to give us the space to act more strategically and all with a global perspective. We hope to be able to share further details of this next month.

Today, I am also delighted to announce some changes to the organisational structure and executive leadership of the Trust, which I believe will help us to achieve our goals and deliver our mission.

Following the decision by David Lynn to retire early, for personal reasons, from full-time work and the position of Director of Strategic Planning and Policy, we have created a new division of the Trust, Strategy. It will be tasked with refining and articulating the Trust’s ambitious vision of improving human and animal health, embedding our new strategic funding framework, and helping us to track our progress. It will nurture and develop our external relationships and influence (in the UK and globally), and sit at the heart of the Trust so it can draw on expertise from across the organisation. It will bring together the existing teams of Strategic Planning and Policy, Evaluation, Communications, Education and Grants Management, along with a new “Incubation Unit” for developing new projects. This last unit will include the Sustaining Health initiative led by Ted Bianco.

I am delighted that Clare Matterson has agreed to lead this new Division as Director of Strategy. Over the past decade, Clare has proved herself to be visionary leader as Director of Culture & Society, where she has overseen a significant expansion of the Trust’s investment in humanities, social science, public engagement and education, as well as launching the critically-acclaimed and much-visited Wellcome Collection.

We hope to appoint Clare’s successor as Director of Culture & Society soon, to continue to build on her inspiring work at a time when the resources available for it are increasing. Clare will look after both divisions until this process is complete. We are also beginning the search for a Director of Innovations to succeed Ted Bianco.

We will also be creating a second new division, People & Development. The greatest asset in any organisation is its people, and I want the development, careers, leadership and recruitment of individuals and teams to be central to discussions at the Executive Board. I also think the Trust could do more to support leadership and personal and team development in our wider research community. To that end, we will appoint a Director of People & Development, with a focus on finding and encouraging talent and leadership both internally and externally.

Finally, recruitment is now advanced for a Chief Financial Officer, to lead the Finance & IT division that has a crucial role in providing assurance and guidance on our spending, as well as bringing creative and resilient technological solutions to enable us in our work. The responsibilities previously held so ably by Simon Jeffreys, who stepped down as Chief Operating Officer earlier this year, will be divided between Finance & IT, People & Development, Strategy and Legal.

Wellcome Trust Research Round-up: 29/09/14

29 Sep, 2014

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

Immune system of newborn babies is stronger than previously thought

The immune system of a newborn baby, although very different to an adult’s, may still be able to mount a strong immune defense, according to new findings that go against the received wisdom on this topic.  Baby, newborn Credit:Anthea Sieveking

The study, published in Nature Medicine and funded by the Wellcome Trust, found that the immune T cells of newborn babies may have the ability to trigger an inflammatory response to bacteria. Up to now, it was generally believed that babies have an immature immune system that doesn’t allow this. Although babies need to protect themselves from the harmful pathogens they are exposed to from birth, it was thought that their T cells were suppressed to some extent to prevent inflammatory damage to the developing child.

Now, a team at Kings College London has discovered that whilst T cells in newborn babies are largely different to those in adults, it is not because they are immunosuppressed. Rather, they manufacture a potent anti-bacterial molecule known as IL8 that has not previously been considered to be a major product of T cells, and that activates neutrophils to attack the body’s foreign invaders.

Deena Gibbons, lead author at King’s College London, says: “We found that babies have an in-built anti-bacterial defense mechanism that works differently to adults, but nevertheless may be effective in protecting them. This may also be a mechanism by which the baby protects itself in utero from infections of the mother. The next stage of our work will be to better understand the pathways that result in the immune cells of newborns being so different to those in adults.”


Statins associated with modest increases in weight and diabetes risk

The mechanism by which statins increase the risk of type 2 diabetes has been investigated in a large-scale analysis from an international team led by researchers from UCL and the University of Glasgow, using information from genetic studies and clinical trials.

HMG-CoA reductase Credit:T. Greenhough & A. ShrivePublished in The Lancet, the work received support from a number of funders including the Wellcome Trust, the Medical Research Council, British Heart Foundation, Rosetrees Trust and National Institute for Health Research University College London Hospitals Biomedical Research Centre.

Among nearly 130 000 participants from clinical trials that previously tested the effect of statins on heart disease and stroke, those assigned statins vs. placebo, or higher vs. lower doses of statins, were noted to have a small increase in the risk of developing type 2 diabetes, of about 12% over a four-year period, and also to gain an excess of 240g (around half a pound) in weight.

“Weight gain is a risk factor for diabetes which might help explain the small increased risk of diabetes observed in people taking statins”, explains co-lead author Dr David Preiss of the University of Glasgow Institute of Cardiovascular and Medical Sciences.

Statins work by reducing the efficiency of a liver enzyme involved in cholesterol production, which causes liver cells to trap more low-density lipoprotein (LDL-) cholesterol from the bloodstream, reducing its circulating level. This mechanism is thought to underlie the efficacy of statins in lowering the risk of stroke and heart disease.


HIV-infected individuals receiving therapy are still susceptible to TB disease

People infected with HIV, but who are stable and taking a combination of potent antiretroviral drugs (known as ART), are still more susceptible to developing TB disease than those who are not HIV-infected because of problems with TB-specific immune responses in their lungs, according to a new study.

HIV particles Credit:R. Dourmashkin

TB is an opportunistic infection which commonly infects and kills people who have HIV. A new study, conducted by researchers at the Malawi-Liverpool Wellcome Trust Clinical Research Programme, explains why people taking ART who have undetectable concentration of HIV viruses in their blood and a high T cell count (indicating a good response to ART and a strong immune system) are still susceptible to developing TB disease.

The study, published in the American Journal of Respiratory and Critical Care Medicine, examined blood and lung samples from 35 HIV-uninfected, 25 HIV-infected ART-naïve (those who were not taking ART), and 50 HIV-infected ART-treated adults.

They found that immune cells found in the lungs called ‘alveolar macrophages’ and T cells that respond specifically to the presence of the TB-causing bacteria or its proteins do not work properly in HIV-infected adults who have taken ART for less than four years, partly explaining why they are susceptible to developing TB disease.

Dr Kondwani Jambo, a postdoctoral fellow funded by the Malawi Health Research Capacity Strengthening Initiative (HRCSI), which is part-funded by the Wellcome Trust, and Dr Henry Mwandumba, a Wellcome Trust Intermediate Clinical Fellow, are among the authors of the study. Dr Mwandumba said: “These findings underscore the need for strategies to augment ART to improve lung immune cell function and reduce the incidence of TB. The use of vaccines that promote repopulation of the lungs with TB-specific immune cells and the use of preventive TB treatments, especially during the early years of ART when HIV-infected individuals are most vulnerable, ought to be considered.”


Image credits:
Newborn baby – Anthea Sieveking, Wellcome Images; Model of human enzyme inhibited by statins – T. Greenhough & A. Shrive, Wellcome Images; HIV particles – R. Dourmashkin, Wellcome Images. 

Image of the Week: Artificial Knee Joint

26 Sep, 2014

B0000523 SEM cobalt chrome tibial tray/artificial knee

Perhaps you see vessels or worm-like structures when looking at our image this week. Or perhaps it looks more like synthetic fibres or metal wires. There’s something quite beautiful about it but also something a little bit unsettling.

Is this a photo of something man-made or organic? You could say it is both! It is part of an artificial knee joint, photographed under a Scanning Electron Microscope. This particular part is called a tibial tray, and attaches to the shin bone (tibia) to help keep the joint stable. This type of knee replacement has what’s known as a porous coated design – you can see gaps between the sections of metal, which allows bone to grow into the replacement joint, reducing the chances of the artificial limb being displaced or becoming unstable. It allows the synthetic and the organic to merge together.

The photo was taken after the artificial knee joint was removed from a patient during surgery and replaced with a new one. Surgery would have taken around three hours and is a larger undertaking than the original knee replacement. We can see the structure so clearly because the tissue has been digested, allowing the metal to be visible. However, traces of the tissue can still be seen. They are a reminder that we are seeing something that was once an important component of someone’s body – part man-made, part organic.

Image Credit: EM Unit, UCL Medical School, Royal Free Campus, Wellcome Images

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

Shaping our Sustaining Health initiative

25 Sep, 2014

The city of New York came to a standstill on Sunday as hundreds of thousands of people joined the People’s Climate march. Chants of “Show me what democracy looks like – This is what democracy looks like” echoed around Times Square as people from over 2000 groups and organisations joined thousands more individuals all wanting to get their voice heard on the issue of climate change. The Wellcome Trust’s Sustaining Health team were also in town to hear from a diverse range of experts, to help us shape our Sustaining Health initiative. Kate Arkless Gray gives a taste of the discussions taking place in New York…
photo 4
“Never before has a species thought its way out of a Darwinian selection process” said Ted Bianco, from the Trust’s Sustaining Health team, opening the discussion ‘Sustaining Health: Linking environment, nutrition and health’.

There is a real sense of energy in New York as the world’s leaders convene for the UN Climate Summit. The whole city is alive with people discussing commitments to change, debating what can be done, and forging new collaborations. Ban Ki-Moon proclaimed that leaders are “not here to talk, but to make history”.

For our own part, the Wellcome Trust, together with the International Research Institute for Climate & Society (IRI), Columbia University Mailman School of Public Health and Meteos, hosted an event to bring together a range of global voices to discuss the links between climate and health. These included public health researchers, economists, investors, social entrepreneurs, climate scientists and more.

We began with Professor Kirk Smith, Convening Lead Author of ‘Human Health: Impacts, Adaptation, and Co-benefits’ the IPCC fifth assessment report, giving an overview of the report’s findings in relation to health.

photo 5

With 190 countries signed up to it (and thus having to sign off the report) getting everyone to agree was not straight forward. Smith explained the report’s strength comes from the number of countries involved, but it was a double-edged sword at times, and the need for unilateral agreement affected the content.

Smith summed up the report by splitting the issue into three eras: The present – where it’s very difficult to assign a significant burden of disease to human-caused climate change to date, although local effects are occurring; the future up to 2050 – where growing health impacts can be expected if adaptation measures are not taken, but could be greatly reduced if they were; and the future post 2050 – where there is a risk in the higher emissions scenarios that exceeds conceivable adaptation potentials, thus leading to major impacts on health, particularly among the poor.

With the scene set, the discussion began. Our panel – Steve Davis, President and CEO, PATH, Ricardo Fuentes Nieva, Head of Research for Oxfam GB, Patrick Kinney, Professor of Environmental Health Sciences, Mailman School of Public Health and Madeleine Thomson, Senior Research Scientist at IRI – gave their reflections and opened up the conversation to the room.

Smith’s assertion that climate change is “the most regressive tax in history” chimed with Fuentes Nieva. Introducing a theme that continued throughout the afternoon, he reminded us that while climate change is a global problem, it doesn’t affect everyone equally. The most vulnerable people, the poorest people, the ones less able to adapt to change, will be at the frontline where climate change exacerbates existing problems.

Two trends – the increasing numbers of vulnerable people, together with a growing increase in inequality – mean that without action, we risk leaving people behind.

The discussion around the role of science and technology included the potential benefits of big data, which led to John Krebs voicing the need for linking data sets and connecting the silos. Anne Johnson highlighted the mismatch in the places with available data and those where action is needed.

John Balbus (NIH-NIEH) pointed out that health is late to the climate impact data-modelling game, which could be an avenue worth exploring, while Madeleine Thomson reminded us of the need to consider whether data is collected and shared in a format that meets the need of people on the ground.
It’s not just researchers that need access to accurate, relevant and fit for purpose data. Health ministers also need access to reliable data, in a format that is useful to them.

Climate change is a global problem, but solutions need to be locally appropriate. What works in one place won’t always work elsewhere, and so far the focus has often been on solutions that work for middle-income settings, rather than the most vulnerable.

photo 2

Another exciting concept is that of ‘Healthy Cities’ however Kinney remarked that despite much activity in this area, there has been little in terms of assessing the cost-effectiveness of measures linking obesity, pollution and city development.

Richard Horton reflected on “Countdown to 2015” – a scientific network set up when it became clear that the millennium development goal on child and maternal mortality would be missed. He suggested that perhaps there could be lessons taken from this collaboration, which tracked indi

cators that mattered to the public as well as to governments. Long-term investment in bringing people together is needed.

The question was raised of how to get corporations involved in the debate and taking action. Understanding the financial markets and changes in the way they are working with technology and health could be key to that.

Other areas touched upon during the afternoon included food security – alternative crops and food sources need consideration, population and family planning – a sensitive issue, which would need careful handling, social networks and use of technology to drive behavioural change, and the collection of metrics on exposure.

Finally, Kirk Smith called for artists, philosophers and authors to help start a cultural revolution to help inform and create debate to combat and survive climate change and protect our future.

It was a gracious, honest conversation, with people from different backgrounds bringing their experience and perspectives to the discussion on linking environment, nutrition and health.

It’s given us plenty of food for thought and we will continue to listen to a wide range views from disparate sectors to inform our decisions on how the Wellcome Trust can have an impact on sustaining health.

You can find out more about the Sustaining Health initiative on on the Wellcome Trust website. A record of the live tweets  from the event in New York using the hashtag #SustHealth are available on the @WellcomeLive twitter account.

Image credits: Kate Arkless-Gray

Reality behind research: 21 years of oral history with Wellcome Witness

24 Sep, 2014

Thousands of scientific papers are published every year, reporting on interesting results, but the standard format – introduction, materials and methods, results, conclusions, references – leaves little space for the social context of the work. For over 20 years, the Wellcome Trust has been supporting Wellcome Witness seminars, which bring together key figures in research to discuss the stories behind the discoveries. Professor Tilli Tansey discusses the Witness Seminars, and on the occasion of the publication of the 50th volume in the Wellcome Witnesses to Contemporary Biomedicine series, reflects on some of the highlights and the remarkable people she met along the way…

Dr Tilli Tansey and Sir Chris Booth, at a Witness Seminar

Dr Tilli Tansey and Sir Chris Booth, at Witness Seminar on post-penicillin antibiotics, 1998 © Wellcome Library, London

On 24th September 1993 we did an experiment in the Wellcome Building at 183 Euston Road. ‘We’ were the Wellcome Trust’s History of Twentieth Century Medicine Group (initially me, Sir Christopher Booth – a retired clinician, and Mrs Wendy Kutner – our secretary for two days a week). The group was set up by the Wellcome Trust in 1990 to try to bring together historians, scientists, clinicians and others interested in studying recent medical history. The aforementioned “experiment” was our first ever Witness Seminar, on the topic of monoclonal antibodies.

Monoclonal antibodies were discovered in the 1970s when it was shown that a single clone (i.e. of genetically identical cells) grown in culture, could be treated so as to produce pure, specific antibodies, which opened up exciting new possibilities of precisely targeted forms of medicine. This was an important discovery to explore and we wanted to get behind the rigid structure of the published scientific papers to hear from those who were there at the time. What really happened, and how and why? What were the key experiments that influenced the work? Who were the main players (including those lesser known names)? What went right, and – what one rarely hears about – what went wrong?

As well as being an important medical discovery, here was another reason we wanted to discuss monoclonal antibodies. The techniques had never been patented in the UK, although American scientists seized on the discovery and did get patents. By the late 1980s this had become a ‘scandal’, seen by some as another example, like the ‘loss’ of British penicillin to the USA in the Second World War, of the inability of naive scientists and their institutions to exploit discoveries commercially.That afternoon, 21 years ago, was fascinating – our witnesses included the two principal scientists involved, César Milstein and Georges Köhler who shared the Nobel Prize in 1984; contemporary colleagues and rivals; administrators and journalists. They were all open and frank (although not necessarily in agreement) about the development of vital techniques in the lab, the role of key personnel, and in particular the role of patents and commercialisation in medical research.

The whole meeting was recorded, transcribed with permission from the speakers, and the tapes and transcript were deposited in the archives of the Wellcome Library for the use of future historians.

We realised that this approach provided insights, details and discussions not available elsewhere and planned a few repeat experiments. In 1996 we decided to publish the edited proceedings, and the following year a volume, optimistically labelled as ‘one’, appeared.

With the continued support of the Wellcome Trust, initially in-house, then at UCL and more recently at QMUL, we continued to develop this technique and have published nearly 60 meetings, mostly in the series Wellcome Witnesses to Contemporary Medicine (formerly Wellcome Witnesses to Twentieth Century Medicine).

In line with the open policy of the Wellcome Trust, all of our material is freely available for use by others.

Over the past 20 years, over 1400 people have contributed to our seminars, including several Nobel Laureates, clinicians and scientists of practically every medical specialty, and patients, technicians, nurses, and journalists, amongst others. I am convinced of the power of this technique in allowing many authentic but diverse voices of modern biomedicine to be heard and proud that we have been able to record the voices behind some great discoveries.

Over the years there are some particular favourites, a few of which I’d like to share.

Dr Ethel Bidwell and Dr Charles Rizza at Witness Seminar on haemophilia

Dr Ethel Bidwell and Dr Charles Rizza at Witness Seminar on haemophilia, Feb 1998 © Wellcome Library, London

One of these is from Dr Ethel Bidwell from our meeting on haemophilia. She was extremely reluctant to attend, telling me over the phone when I invited her that she had nothing to contribute. But I knew, from reading the journals of the time and from a casual conversation with a haematologist friend that she was the person who, in the 1950s, had discovered factor VIII, the first reliable treatment for haemophilia, and I wanted to hear her story.

Fortunately I managed to persuade her to come, and when she arrived we persuaded her to talk about her early work. Trained as an enzyme chemist, she joined the MRC Blood Coagulation Lab in Oxford to work on gas gangrene, but finding no-one there interested in her work, she decided to see if she could ‘make something from animal blood’ to treat haemophiliacs.

Ethel described the primitive conditions in which she collected blood from the local abattoir, where the slaughterhouse men always wanted her to have blood from the prize animals that won rosettes. She reckoned that ‘ancient old cows were much better’.

Page on haemophilia in volume 50

Page on haemophilia in volume 50

After pouring the blood into a big glass Winchester bottle she would strap it to the back of her Vespa scooter and gingerly ride back to the lab, constantly worried that she would have an accident and the blood would spill all over the road.Another memorable witness was from the same meeting, Clifford Welch. Himself a mild haemophiliac he described how life ‘severely shook up’ in 1930 when he was five and triplet brothers were born, all of whom had haemophilia. He vividly described the limited availability of treatment, the frequent trips to Barts Hospital in London, as one or other brother, sometimes two or more together, were admitted. He gave a particular mention of the ‘miracle’ of blood transfusions from their mother that saved their lives on numerous occasions.

picture 4 WWDr Usama Abdulla and Mr Thomas Brown at Witness Seminar on obstetric ultrasound

Dr Usama Abdulla and Mr Thomas Brown at Witness Seminar on obstetric ultrasound, March 1998, © Wellcome Library, London

Tom Brown, a star witness at the seminar on Obstetric Ultrasound, recalled his early days as an engineer in the Glasgow shipyards, working on using ultrasound as a non-destructive way to detect flaws in metals being used to build submarines. Hearing that the Professor of Midwifery was trying to find ways of visualizing the foetus in utero, Tom looked him up in the phone book, gave him a call, and their initial conversation led to the collaboration that developed the machines and procedures that are now routine in every ante-natal department.

These are the sort of insights that we aim to capture – the personal tales and memories that have no space in traditional scientific publications, but shed light on the reality of iconic research.It is not only individuals, but sometimes whole groups that are particularly memorable. We have held a number of meetings to examine the history behind large scale survey work, including NATSAL (National Survey of Sexual attitudes and lifestyles); ALSPAC (Avon Longitudinal Study of Parents and Children); and the work of the MRC Epidemiological Research Unit in South Wales. The little-heard voices of the interviewers themselves provided intriguing details.

Wendy Williams described how, before working on NATSAL, potential interviewers had to be ‘desensitised’ by listening to every known term connected with sexual activity so they would never be surprised by anything during an interview. After this two-day barrage, several male interviewers dropped out feeling unable to continue, whilst most of the women remained.

It’s not always easy to track down all the people that we’d like to hear from. Locating the scientists and clinicians who were involved in particular fields is comparatively easy, since even in retirement they can usually be traced through their former institutions or professional organisations. To find the less well-known contributors however we have to be a little more creative, using pension and social clubs, Christmas card lists, friends-of-a-friend-of-a-friend connections, for example.

ALSPAC Witness Seminar at the Wellcome Trust, London

ALSPAC Witness Seminar at the Wellcome Trust, London, 2011 © Wellcome Library, London

Finding one technician can lead to others; one patient may be in touch with fellow sufferers; one fund-raiser can link us with associates; and one retired midwife may keep up a lively correspondence with friends that suddenly gives us access to a wide network.Sometimes, we are simply too late – the key figures, whether well known or not, are no longer with us or no longer able or willing to travel to London to participate. Conversely we have occasionally been too early – in a still active field appropriate contributors may be too busy or impatient to take an afternoon off to consider the historical dimensions of their work.As we celebrate our 21st birthday, we are publishing the 50th volume of Witness Seminars. This anthology of extracts from all our previous meetings is titled ‘Monoclonal Antibodies to Migraine’, reflecting the scope of biomedical subjects we have tackled over the years. These include issues of professionalisation and specialisation within medicine, such as the creation and impact of sports medicine; medical physics; intensive care and clinical pharmacology.

We have heard from eye-witnesses involved in the development and use of new treatments for conditions including haemophilia; leukaemia; cystic fibrosis; and peptic ulceration. The development, problems and potentials of treatments including hip replacement surgery; heart transplants; and renal dialysis have all been debated, as have the impact of technology such as obstetric ultrasound and NMR and MRI.

As the Government Chief Scientific Adviser, and former Director of the Wellcome Trust, Sir Mark Walport says in his foreword, this volume is full of gripping vignettes and stories – we hope you’ll enjoy reading them as much as we have enjoyed collecting them over the years.

Now supported by a Wellcome Trust Strategic Award, the project continues until early 2017, focussing on five main themes: clinical genetics; neurosciences; global and infectious diseases; ethics in medical research and practice; and medical technology. With so many topics to explore, perhaps the 100th volume will be along earlier than expected!

You can find out more about the Wellcome Witness series on the History of Modern Biomedicine Research Group’s website or you can follow them on Twitter or connect via Facebook. The Makers of Modern Biomedicine project is supported by a Wellcome Trust Strategic Award.

Researcher Spotlight: Professor Helen McShane

22 Sep, 2014

DSC_6454Professor Helen McShane is a Professor of Vaccinology and Wellcome Trust Senior Clinical Fellow at Oxford University, where she leads a programme of research to develop a new vaccine for Tuberculosis (TB).  Here she gives an insight into the international nature of TB research and her motivations for starting, and continuing, research in this field.

What are you working on?

Tuberculosis vaccine development and tuberculosis immunology.

What does your average day involve?

There’s no such thing as an average day! And that’s partly why I enjoy it so much.

All my days involve an early start, and often the only time I can get to my email is either first thing in the morning, before my children wake up, or late at night after they’ve gone to bed. Although as they get older the window between them going to bed and me going to bed is shrinking!

I spend a lot of time on the telephone. We are currently conducting clinical trials in South Africa, Senegal and Uganda, and collaborating with two industrial partners on clinical trials in the UK. We have regular teleconferences on each trial to keep in touch and trouble-shoot any issues in real time. I also spend a lot of time interacting with my collaborators and partners in the US including the Gates and Aeras Foundations. Managing the time zones and fitting things around everyone’s schedules can be challenging!

I meet with my PhD students and post-docs to go through their data, and discuss next steps. Once a week I do an HIV clinic, which I love. It keeps my feet on the ground! In an HIV clinic you can see life at its rawest – but it’s also a great example of evidence-based medicine. I’m usually writing at least one grant application at any one time, and two or three manuscripts which someone in my group or a collaborator has written that need reviewing.

At least once a month I’ll travel somewhere – either for an international conference (where I am often asked to speak) or a field visit to one of the African centres. I try to keep the trips short and the travelling to a minimum because of my children, but I love visiting the field sites in Africa. I am fortunate to collaborate with some amazing people, and visiting the sites in Africa, where TB (and HIV/AIDS) is such a problem, reminds you why it is all worthwhile and what it is we are working for.

Why is your work important?

TB remains a very significant cause of disease and death throughout the world – in 2012 there were 8.6 million new cases and 1.3 million deaths. Co-infection with HIV (which makes people more susceptible to TB) and the emergence of drug resistance have made the problem worse. We urgently need better tools with which to control this epidemic and vaccination is the most cost-effective way to control any infectious disease.

In my group in Oxford, we developed the first new TB vaccine to enter into clinical testing, and the first vaccine to enter into efficacy testing. We’re currently testing an aerosol version of the vaccine, to induce immunity in the lungs, which is where TB enters the body.

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

I hope to contribute to the development and licensure of an effective TB vaccine.

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

As a junior doctor I worked in Brighton at the beginning of the AIDS epidemic in this country and I became interested in HIV, and infectious diseases. At that time we had no drugs to treat HIV, and all of my patients were dying. From there I moved to Oxford and then London, to gain more experience in HIV and infectious diseases.

It was in London, when I was learning to do bronchoscopies on patients, that I became interested in TB and decided I wanted to do some basic research in this area. I came to talk to Adrian Hill in Oxford, who at the time was starting a big programme of research in malaria vaccine development, and persuaded him to let me start working on TB vaccine development in parallel.

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

Wellcome funding has been instrumental to my career development. After receiving an MRC Clinical Training Fellowship to fund my PhD, I was lucky enough to secure a Wellcome Clinician Scientist Fellowship. This allowed me to complete my clinical training, continue my research programme, and have a day off a week to look after my two children. I was then awarded a Wellcome Senior Fellowship, which I have since renewed.

In addition to that personal programme support, the Technology Transfer division of Wellcome has also been very supportive, and I have received a Technology Transfer grant and a Strategic Grant from the Trust to fund the overseas vaccine programme in South Africa.

Throughout my now 13 years as a Wellcome fellow, the Trust has been enormously supportive, flexible and approachable. I have felt very lucky to have its support.

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

Why is developing a TB vaccine so difficult?

Which question about your work do you most dread?

Anything to do with badgers!

Tell us something about you that might surprise us…

I love wild swimming, and swimming in the sea, regardless of the temperature!

What keeps you awake at night?

How I can continue to raise funding to keep the wonderful team of post-docs, RAs, clinicians, nurses and project managers I am lucky enough to have working with me in my group.

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

Ironically, it may be the advice of my maths teacher, in a South London comprehensive, who was of the view that I should be a housewife! I was stubborn and contrary enough to use this as the final incentive I needed to work hard and get to Medical School.

The “chain-reaction” question set by our previous spotlit researcher Prof Mike Barrett is this: If you weren’t a scientist, what would you be?

If I weren’t a scientist, I’d be a doctor! But to be able to do both is wonderful.

You can find out more about Professor Helen McShane’s work on her researcher profile. You can also read about Professor McShane’s recent research in the following papers: Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG and Safety and immunogenicity of a candidate tuberculosis vaccine MVA85A delivered by aerosol in BCG-vaccinated healthy adults.

Image of the Week: Ebola vaccine trial

19 Sep, 2014

Ebola vaccine

This week’s image of the week is shows Dr Felicity Hartnell administering the first dose of a trial Ebola vaccine to volunteer Ruth Atkins.

Ms Atkins, who has previously worked as a nurse in the NHS, said: “I volunteered because the situation in West Africa is so tragic and I thought being part of this vaccination process was something small I could do to hopefully make a huge impact”. She first heard the call for volunteers when listening to Professor Adrian Hill, who is leading the research at the University of Oxford, on the radio.

“I did not realise until today how many people behind the scenes have worked extra and unsociable hours to get this to trial so quickly. The team has been so helpful and supportive, coming in for early morning appointments to allow me to take part before I go to work” she said.

The Wellcome Trust co-funded this rapid response vaccine safety trial with the Medical Research Council and Depart for International Development. The candidate Ebola vaccine has been co-developed by the US National Institutes of Health (NIH) and GlaxoSmithKline (GSK) to protect against the Zaire species of Ebola, which is the one circulating in West Africa.

With current WHO figures putting the death toll from the current Ebola outbreak at almost 2500 (as of September 13th) it is vital that action is taken to contain the disease.

Find out more about the Wellcome Trust’s fast-tracked funding for Ebola research on our website.

Image credit: Wellcome Trust

Sustaining Health: Linking environment, nutrition and health

18 Sep, 2014

The Wellcome Trust is increasingly aware of the links between environment, nutrition and health. To help examine the role of science and technology on climate and health, and discuss potential levers for change, the Wellcome Trust is co-hosting an event to coincide with the UN Climate Summit in New York. Saskia Heijnen of the Trust’s Sustaining Health team explains why this is important…

N0024246 Bangladeshi women. Harvesting crops.

Health has not traditionally been the first thing that comes to mind when the topic of climate change is raised, but connections are now being made. For example, the latest IPCC report, which provides a synthesis of the scientific and technical evidence of climate change, now places a greater focus on potential health impacts. This is important because health can be impacted in a variety of ways. Examples include extreme weather events such as heat waves and flooding, the spread of climate-sensitive vector-borne diseases, and of course climatic impact on water supply and agricultural production.

Shifting weather patterns and water scarcity are already an issue in many parts of the world as discussed at World Water Week earlier this month. And research has shown that increased carbon dioxide levels in the atmosphere can decrease the nutritional content of our major food crops. With a growing population in a changing world, we need to investigate ways of addressing these issues if we want to safeguard human health for generations to come.

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The good news is that momentum is building – the first ever WHO Conference on Health and Climate took place at the end of August, and next week there is a UN Climate Summit that coincides with New York Climate Week and has health on its agenda – but there is still more to be done.

The buzzwords in the field are “nexus” – a series of connections, frequently used in the context of relationships between water, energy and food – and “resilience”, adapting to better prepare for the heat, weather extremes, food insecurity and spread of infectious diseases. We, and others, believe that more connections need to be made between sectors and organisations to identify levers for change, and we hope that our Sustaining Health initiative will help in this.

The Wellcome Trust’s Sustaining Health initiative will continue to fund research to develop and promote climate-smart strategies and improve surveillance and control of climate sensitive infectious diseases such as cholera, malaria and dengue. We also want to help to bring disparate disciplines together to discuss potential solutions and look at the issues holistically.

Screen Shot 2014-09-17 at 15.05.18On Monday 22nd September, the first day of New York Climate Week, we are co-hosting an event to coincide with the UN Climate Summit. This interactive expert discussion will explore the issues that link environment, nutrition and health with colleagues at Columbia University Mailman School of Public Health, the International Research Institute for Climate and Society, and the think-tank Meteos. We aim to help drive discussions on the future of climate and health and explore how collaborations can make a real impact.

We will be there to listen and we’ll be using the outcome of the discussion to help shape the Wellcome Trust’s approach to Sustaining Health. It’s an area that can’t be ignored.

The Wellcome Trust’s Sustaining Health: Linking Environment, Nutrition and Health is taking place at 2:30pm-6:00pm in New York (7:30pm-11:00pm BST). We will be live tweeting from the event from the @WellcomeLive account using the hashtag #SustHealth. Please do get involved with the discussion online using the hashtag, or by sharing your thoughts below. You can find out more about our Sustaining Health initiative on our website.

Image credits:  N. Durrell McKenna, Wellcome Images, United Nations Photo CC-BY-NC-ND on Flickr, Climate Week NYC

Pick of the science pics at the London Film Festival 2014

17 Sep, 2014

Audiences with an appetite for films inspired by science will have their thirst well and truly quenched by this year’s BFI London Film Festival which opens on 8th October with the Alan Turing biopic, The Imitation Game. We are delighted that three Wellcome Trust-supported films are part of the festival, which sees thirty films in the programme that explore the wider cultural, social and personal contexts of science. Subjects include autism, transgender bodies, ageing, disability, mental health and more. With so much to choose from, we asked Meroë Candy, Film and Drama Development Manager at the Trust, to give us some recommendations of what to watch out for…

Bjork: Biophilia Live

The culmination of Bjork’s science and art odyssey, Biophilia Live is an indescribable experience. On one level it is a film of her final performance of the Biophilia tour at London’s Alexandra Palace, on another it is a grand, experimental art piece which intertwines found and archive scientific footage with live music to re-connect its audience with our place in the natural world.

In a masterful piece of understatement, co-director, Nick Fenton says “Let’s not get too excited. It is only a concert film with some volcanoes and a few viruses; thunder and lightning; plankton and planets. Not forgetting Björk, the jellyfish, David Attenborough and the beautiful sounds of the choir Nobili.”

Bjork worked with Peter Strickland and Nick Fenton to encapsulate the soul of the Biophilia project on screen who consulted with Dr Adam Rutherford and Wellcome Images in the sourcing of imagery. Peter Strickland has another ‘science-inspired’ film in the festival The Duke of Burgundy about the sexual power dynamic between two lepidopterists.

Biophilia Live is the Sonic Gala premiere film and will screen on October 9th and 10th, 2014.

Electricity

Image credit: Paul Stephenson

Image credit: Paul Stephenson

Agyness Deyn plays Lily, a young woman who experiences regular epileptic seizures, in the film Electricity, written by Joe Fisher and directed by Bryn Higgins.

Lily embarks on a search to find her estranged brother – a journey which pushes her to her limits physically and emotionally. Festival programmer Kate Taylor says “Visualising Lily’s physical experience in ambitiously cinematic ways, Electricity speaks of the experience of living a constantly medicated life, and how far people go to gain or lose control.”

Both lead actor and director worked with Dr Gonzalo Alarcon to ensure the film portrays a unique and authentic experience of living with epilepsy.

Electricity will screen on October 14th and 18th, 2014 and will be released by Soda Pictures on 5th December.

Abandoned Goods

Abandoned goods 'a camping hospital', AaH, p40

Short essay film Abandoned Goods, directed by Pia Borg and Edward Lawrenson and produced by Fly Film, documents the artworks created by people detained in Netherne psychiatric hospital between 1946 and 1981. Today around 5,500 pieces survive, assembled together as the Adamson Collection, one of the major bodies of British ‘asylum art’ – examples of which are held in the Wellcome Library. The film has already been awarded the Golden Pardino for the Best International Short Film at Locarno Film Festival.

Abandoned Goods will be screened on October 13th. 

Other films to look out for at the festival include The Falling, which is inspired by historical accounts of collective hysteria; The Tribe, a Ukrainian film about a boarding school for deaf young people which contains no spoken language, only sign language; X + Y, the story of a maths genius with autism; and The Possibilities are Endless, about pop star Edwyn Collins’s recovery from stroke.

Tickets for these films, and other London Film Festival screenings, go on sale to the public on the 18th September. You can find out more about the Wellcome Trust’s work to support film and drama here.

Wellcome Trust Research Round-up: 15/09/14

15 Sep, 2014

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

Risk of Ebola emergence mapped

A new map identifies areas where animals are likely to be infected with the Ebola virus. The map is a first step towards understanding where future outbreaks of the disease may occur.

The map, based on a model created by Oxford University scientists, predicts that in animal populations, the Ebola virus is likely to be circulating across a vast swathe of forested Central and West Africa. This area covers seven countries which have already reported Ebola transmission from animals to humans, as well as 15 more countries which are likely to be at risk.

A report of the research, which was funded by the Bill & Melinda Gates Foundation and the Wellcome Trust, is published in the open access journal eLife.

Screen Shot 2014-09-15 at 13.58.12

So far there have been only 30 confirmed cases of Ebola transmission from animals to humans – the virus is difficult to catch from animals and most instances of transmission are thought to arise from close contact through hunting or butchering infected animals. However, current international efforts to control outbreaks of Ebola in humans in West Africa, and reports of a separate outbreak in the Democratic Republic of Congo, highlight the importance of being prepared for future outbreaks of the disease so that they can be stopped early.

Whilst rare as a human disease, Ebola virus is thought to be present in many animal populations, especially bats, which can carry the virus without it being lethal to them.

The team generated the model by bringing together available data on where human and animal infections have occurred from 1976 to the present and looking for similarities in environmental factors such as vegetation, elevation, temperature, and estimated distribution of bat populations. The researchers were then able to create a map identifying similar areas where the virus is likely to be carried by animals and there is a risk of transmission to humans triggering future outbreaks.

Binge drinking in pregnancy may affect children’s mental health and school results

Binge drinking during pregnancy may increase the risk of mental health problems in 11 year old children and can have a negative effect on their school examination results, according to research published in the journal European Child & Adolescent Psychiatry.

Increased risk of mental illness, particularly hyperactivity and inattention, was found by researchers even after a number of other lifestyle and social factors were taken into account. The findings build on earlier research on the same children that found a link between mothers binge drinking during pregnancy and the child’s mental health when aged four and seven, suggesting that problems can persist as a child gets older. Other effects, such as on academic performance, may only become apparent later in a child’s life.

C0014971 Glass of beerBinge drinking was defined as drinking four or more units of alcohol in a day on at least one occasion during the pregnancy. The women were asked about their drinking pattern at both 18 and 32 weeks of pregnancy and again when their child was aged five.

At age 11, parents and teachers completed questionnaires about the children’s mental health. Information about academic performance was based on the results of the Key Stage 2 examinations taken in the final year at primary school.

Speaking about the findings, the report’s main author, Professor Kapil Sayal from the University of Nottingham, said: “Women who are pregnant or who are planning to become pregnant should be aware of the possible risks associated with episodes of heavier drinking during pregnancy, even if this only occurs on an occasional basis.

“The consumption of four or more drinks in a day may increase the risk for hyperactivity and inattention problems and lower academic attainment even if daily average levels of alcohol consumption during pregnancy are low.”

The research was conducted using data from more than 4,000 participants in the Avon Longitudinal Study of Parents at Children (ALSPAC), which is funded by the Wellcome Trust and the MRC.

Scientists reset human stem cells to earliest developmental state 

Scientists have successfully ‘reset’ human pluripotent stem cells to the earliest developmental state – equivalent to cells found in an embryo before it implants in the womb (7-9 days old). These ‘pristine’ stem cells may mark the true starting point for human development, but have until now been impossible to replicate in the lab.

B0006251 Human embryonic stem cellsThe discovery, published in Cell, will lead to a better understanding of human development and could in future allow the production of safe and more reproducible starting materials for a wide range of applications including cell therapies.

Human pluripotent stem cells, which have the potential to become any of the cells and tissues in the body, can be made in the lab either from cells extracted from a very early stage embryo or from adult cells that have been induced into a pluripotent state.

However, scientists have struggled to generate human pluripotent stem cells that are truly pristine (or naïve). Instead, researchers have only been able to derive cells which have advanced slightly further down the developmental pathway. These bear some of the early hallmarks of differentiation into distinct cell types – they’re not a truly ‘blank slate’. This may explain why existing human pluripotent stem cell lines often exhibit a bias towards producing certain tissue types in the laboratory.

Now researchers led by the Wellcome Trust-Medical Research Council (MRC) Cambridge Stem Cell Institute at the University of Cambridge, have managed to induce a ground state by rewiring the genetic circuitry in human embryonic and induced pluripotent stem cells. Their ‘reset cells’ share many of the characteristics of authentic naïve embryonic stem cells isolated from mice, suggesting that they represent the earliest stage of development.

“Capturing embryonic stem cells is like stopping the developmental clock at the precise moment before they begin to turn into distinct cells and tissues,” explains MRC Professor Austin Smith, co-author of the paper. “Scientists have perfected a reliable way of doing this with mouse cells, but human cells have proved more difficult to arrest and show subtle differences between the individual cells. It’s as if the developmental clock has not stopped at the same time and some cells are a few minutes ahead of others.”

In other news…

Dr Dan O’Connor, Head of Medical Humanities at the Wellcome Trust, is speaking at the WHO in Geneva on Thursday this week on the topic of ‘Social Media and Research: Opportunities and Ethical Challenges’. The event is being broadcast over the internet via a webinar.

Congratulations to Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome Trust-MRC Institute of Metabolic Science and Director of the MRC Metabolic Diseases Unit, University of Cambridge, who was awarded the Zulch prize last week.

Image credits: Ebola map – Oxford University, Glass of beer – Wellcome Library, London, Stem cells – Annie Cavanagh, Wellcome Images

Image of the Week: DNA Fingerprinting

12 Sep, 2014

B0005956 The first DNA fingerprint

This week’s image of the week is one for all the detectives out there. It’s an image of the first ever DNA fingerprint, produced almost exactly 30 years ago, by Professor Sir Alex Jeffreys at the University of Leicester.

“My life changed on Monday morning at 9.05am, 10th September 1984. What emerged was the world’s first genetic fingerprint,” he says.

The image was processed in the university’s darkroom – “I took one look, thought ‘what a complicated mess’, then suddenly realised we had patterns,” says Jeffreys. “There was a level of individual specificity that was light years beyond anything that had been seen before”.

‘Eureka’ moments are few and far between in science (despite what Hollywood might have you believe), but this really was the beginning of a whole new field of science. “We could immediately see the potential for forensic investigations and paternity,” says Jeffreys, “my wife pointed out that very evening that it could be used to resolve immigration disputes by clarifying family relationships”.

During the following year, the first immigration case and the first paternity case had been solved using DNA fingerprinting, and the first identification of identical twins using the technique had also taken place. The first criminal investigation to include DNA fingerprinting evidence took place in 1986.

The techniques used for DNA profiling have been updated and optimised since this first image was developed in the darkroom 30 years ago. From helping solve crimes; determining people’s innocence and proving family relationships, DNA fingerprinting is now firmly a part of the forensics tool-kit.

Image Credit: Alec Jeffreys, Wellcome Images

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

 

Unknown unknowns: Is there a selection bias against null results?

11 Sep, 2014

neg image

As a large funder of biomedical research, the Wellcome Trust is keen to ensure that the findings of that research are widely and openly shared. There is a body of evidence that indicates a bias against writing up and publishing certain types of result. Jonathon Kram and Adam Dinsmore, from the Wellcome Trust evaluation team, discuss why this could create a barrier to scientific progress…

There is a lot of pressure on academic researchers. Rightly or wrongly, it is widely held that researchers must publish prodigiously and secure funding consistently to advance their careers and that their research outputs must achieve high ‘impact’ to be of value.

An unintended consequence of this ‘impact culture’ may be a publication bias against research findings whose implications are not immediately obvious, or which may be deemed less novel, interesting, or eye-catching. Some research suggests that this bias may extend to research that yields negative and/or null findings.

There are a few definitions of ‘negative finding’ currently in use, but the idea of significance is central to the concept. A negative result fails to reject the null hypothesis –the proposition that no significant effect is present – within the bounds of an experiment and to a level of statistical rigour. This can occur when a treatment is found to have no greater efficacy than placebo, or when no difference is found between two distinct groups of people (e.g. conservatives and liberals) on some variable of interest.

That said, the term is also used to refer to findings of slightly different but related kinds, including:

  • No correlation found

    No correlation found

    Incremental improvements: Minor refinements to previously reported hypotheses (e.g. where a previous result can only be replicated in certain conditions).

  • Refutations: Results that defy expectation, whether that’s the previous scientific consensus or a researcher’s original intent.

A bias against sharing statistically insignificant results (alongside incremental refinements and refutations) could have detrimental effects to the progression of science and our knowledge. Researchers could waste time pursuing hypotheses which have already been disconfirmed. Clinicians could make treatment decisions based on incomplete evidence. The time and energy of human participants could be wasted in research studies which were never subsequently reported.

Worryingly, there is some evidence that this is already happening.

Hopewell et al (2007) found that research papers which reported statistically significant results were approximately four times as likely to be published as their negative counterparts. The work of Daniele Fanelli (2012) suggests that the proportion of papers publishing negative findings may be decreasing over time; in 2007 just 14% of papers indexed by ISI which declared to have tested a hypothesis reported a negative finding, down from 30% in 1990. Recently Franco et al (2014) found that negative findings are less likely to be written up for publication than more positive results.

Several attempts have been made to encourage the publication of negative findings. BioMed Central’s Journal for Negative Results in BioMedicine has published articles which either report negative findings or discuss their place in science since 2002, while Open Access publishers PLOS One and PeerJ encourage the submission of any scientific results including negative findings.

Away from conventional publication the online datahub FigShare actively encourages the upload of datasets containing null and negative findings, without requiring that the researchers responsible for them prepare a full manuscript for submission.

Credit: Wellcome Library

Credit: Wellcome Library

As a research funder, we are keen that all research findings be accessible and presented to the world; including those that describe a breakthrough, disprove a theory or demonstrate a null result. Everyone in research has an opinion of what makes “good science”, from the researchers through to the readers of a paper. Researchers, journal editors and peer-reviewers all make value judgments about what’s worth telling the rest of the world about. However, if there are processes in play that inadvertently (or advertently) discriminate against the availability of a certain type of result and its data, we risk needless repetition of research and, potentially worse, proliferation of apparent knowledge that may be wrong.

Through the open access movement and the potential of digital technologies, we have the opportunity to enable accessibility to all the findings of research and reduce research waste. If the studies cited above accurately reflect a bias against negative findings in the biomedical literature, then it is the duty of all stakeholders in the delivery of science and knowledge to engage with the issue and explore ways of correcting it.

There is no benchmark to measure the progress of science against but there are hints that there may be a lot of wasted effort caused by our attitude towards negative findings and their unloved siblings. It is only by building a stronger evidence base around negative findings, and exploring the factors that influence publication bias, that we can explore the severity of the problem and make steps towards improving the health of science.

The Wellcome Trust policy position on research involving human participants states that negative results and full disclosure are expected. We are committed to maximising the availability of and value of research data.

How to return to a research career after a break from the lab

10 Sep, 2014

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The Wellcome Trust Research Career Re-Entry Fellowships (RCREF) support people who want to return to science following a substantial break (2 years or more). Getting back to a career in research is not just a matter of funding, and it may be hard to know where to start. With this in mind, the Trust has created a guide for people thinking of taking a break from research, or planning to return to a research career in biomedical/public health. Shewly Choudhury, from our Science Division helped put the guide together with a group of the current and former RCRE Fellows, and speaks to two members of the this group who contributed their experiences to this high-level guide…

“I took a 10-year break from research for family reasons, during which time I combined childcare with science-writing work” explains Jessica Buxton, a former RCRE Fellow now at UCL. She returned to full-time research in 2009, but not without some trepidation.

Christiaan van OoijFor Christiaan van Ooij, leaving bench science behind originally felt like a permanent step. “As time went by, I missed it more and more” he says, “but thought that I was not eligible (or hopelessly uncompetitive without an active research programme) for any Fellowship that would support a continuation in science”. Christiaan returned to full-time research in 2011.

These are common concerns, but taking a career break needn’t be the end of your research career. There are a number of funding schemes out there, including the Wellcome Trust Research Career Re-entry Fellowship, which can support a return to science and we hope that our new guide will be help to answer some of the questions you might have. The guide also describes some of the different Fellowships that support a return to research after a break of several years as well tips that may help you to produce a more competitive proposal.

Here are some of Christiaan and Jessica’s tips for getting back into scientific research:

Be prepared

“It’s hard work, but if you were passionate about science before your break, then the chances are that the effort required to get back into a career you love will be well worth the effort” says Jessica. There is a lot of competition for Fellowships, so ensure that you thoroughly prepare for your application and interview.

Get up to date

Find out what’s happening in your field and what’s changed since you left the lab. There is a wealth of resources online, including open access articles, podcasts, and science news services. “Contacting former colleagues or following scientists on Twitter is another good way to hear about important new advances in your field” says Jessica. For Christiaan his non-lab work also helped him keep up his connections: “I was working as an editor at a microbiology, which allowed me to stay on top of the developments in my field and maintain contacts with former colleagues”. “This made it a lot easier to incorporate the latest technologies in my research plan and update it with the latest findings” he says.

Be realistic

Returning to a career in research will take time and energy. “If possible, try and time your return to fit around your other commitments and the support available” advises Jessica. “In my case, returning to full-time research coincided with my husband launching his own business and working from home, so he was able to take over the ‘parent-taxi’ duties”.

Find a good mentor

Having someone to support you and help you navigate your return to research science can be a real help. They can help you plan the steps on your journey and introduce you to people and inspire you to try new things.

Ask for help

It is inevitable that things will have changed in the time that you’ve been away. When you return to the lab, don’t be afraid to ask how a new technique works, or for advice on the best way to tackle your research question. “Most people are very happy to share their expertise” says Jessica.

Plan for the future

Jessica BuxtonOnce you’ve returned to research, the challenge is to stay – for that you’ll need publications, ideas, funding and supportive collaborators. Early on in your post-break career, you should try to identify your long-term research goals, and stay focused on what you need to do to achieve them. Have open conversations about paper authorship at the start of projects.

So was the hardwork worth it? “Once I had overcome the initial terror of donning a lab coat and picking up a pipette for the first time in a decade, the experience of working with enthusiastic students at the start of their careers made me realise how much I missed being a researcher” says Jessica.

“Returning to science has been a wonderful experience” says Christiaan, “Being back in the lab on a daily basis has been a wonderful experience; the time away from it has certainly allowed me to see what a great job it is”.

You can access the “Returners’ guide to research: Getting back into research after a career break” and find out more about the Wellcome Trust Research Career Re-entry Fellowship scheme on the Wellcome Trust website.

 

Researcher Spotlight: Professor Mike Barrett

8 Sep, 2014

Professor Michael BarrettMike Barrett is Professor of Biochemical Parasitology and Director of Glasgow Polyomics and a member of the Wellcome Trust Centre for Molecular Parasitology at the University of Glasgow. His work involves interpretation of enormous datasets, with a core focus on drug action and resistance in protozoa. We asked Michael to explain his work and share some of the highlights of his career…

What are you working on?

My core research revolves around identifying how protozoa become resistant to drugs and how drugs work.

This work lead to me founding “Glasgow Polyomics”, where we use state of the art technology to collect data on genomes, proteomes and metabolomes. We do this in an informatics-rich environment, enabling us to optimise interpretation of these huge datasets.

Genomics is the best known of these technologies – most people are familiar with the fact we can now systematically generate sequence information on whole genomes relatively easily. Proteomics looks at all of the proteins in a given system and metabolomics quantifies the small chemical building blocks from which everything is built. We really can dissect life down to its constituent pieces. The great strides in reductionist biology are more or less complete.

The challenge, however, has been to understand how these component pieces fit together to create “life”, which is very much more than the interaction of numerous inanimate chemicals. We now apply polyomics at every level of biological research. I am fortunate in having two fantastic teams in parasitology and in polyomics, teams of people with absolute dedication and amazing skills sets.

What does your average day involve?

As I’m split across two campuses, one where my parasitolgy research team works, the other where Glasgow Polyomics resides, I carry my time between sites. Mornings are usually spent strategically planning research at either site, talking to team members about experiments and prioritising timetables. Afternoons then give me the opportunity to write papers, grant proposals or deal with the myriad of queries stemming from our research.

Why is your work important?

Learning how drugs work against protozoa and how parasites become resistant to drugs is necessary given the importance of drugs in our efforts to control the devastating diseases caused by parasitic protozoa.

Trypanosomes in blood

Scanning electron micrograph of trypanosomes in blood, courtesy of Dr Laurence Tetley

Human African trypanosomiasis, sleeping sickness, reached staggering levels by the end of the 20th Century, an with estimated 300,000 people infected.

I was privileged to be involved in bringing a new compound forward through the early part of the 21st Century, and was amazed to see that the implementation of serious clinical trials alone was enough to have a major impact on the disease.

Since then other new compounds have come forward, money has been raised, and a concerted international effort has bought reported cases of sleeping sickness down to fewer than a total of 7,000 reported cases.

As part of our efforts to understand how drugs worked we introduced the new technology of metabolomics to trypanosome research about ten years ago, and have steadily introduced ever more sophisticated techniques to gain information on the inner workings of parasites.

The technology, though, is generic and we quickly began to use metabolimics to look at biological changes associated with drug action in a multitude of systems, as well as to see how biochemistry is perturbed in different disease states. Since genes and proteins are also part of the information cascade that leads to these changes in biochemistry we also incorporated genomics, proteomics and metabolomics into a single site, called “Glasgow Polyomics”.

Michael Barrett with metabolomics data emerging on an Orbitrap Q-Exactive

Over the last three years we have carried out several hundred projects ranging from the discovery of new biomarkers for stroke, and how drugs act in a multitude of diseases (including rheumatoid arthritis, malaria and bacterial sepsis) to investigating the fluctuating state of health of wildebeest by analysis of metabolites found in their tail hairs.

The metabolomics team are using mass spectrometry to study the authenticity of Burns’s poetry and have even been asked to study Martian rocks for isotopes that might indicate life on Mars!

As a Scottish-based facility, showing the public how whisky can be described in terms of its chemical composition – determined using the same machinery we use to look at the chemical composition of people’s body fluids – has been fun too.

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

My immediate hope is that our work on sleeping sickness will make a positive contribution to the international effort underway with a hope of eliminating that disease by 2030. Longer term I hope that in having set up Glasgow Polyomics we can contribute to the amelioration of numerous other diseases.

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

As an undergraduate in Zoology at UCL I went on an expedition to the Usumbara mountains in Tanzania in 1985. The inequalities in health I witnessed there were eye-opening. This was at the beginning of the molecular revolution, and it seemed we should be readily able to understand the causes of disease and also to defeat them. I decided then to carry out a PhD in Parasitology and have continued in this area until now.

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

Wellcome Trust funding has been critical throughout my career. From my first post-doc, my first project grant as an independent investigator, through to today the Trust has been a key funder in my research.

Of course this goes back to Sir Henry Wellcome’s own interest in tropical diseases which has meant the Trust continued to back research in this area even when it had become unfashionable elsewhere. Today, the funding the Trust provides through its Institutional Strategic Support Fund (ISSF) award is the cornerstone of our developments at Glasgow Polyomics. The core funding of the Wellcome Trust Centre for Molecular Parasitology has also been vital on enabling us to apply new technologies such as those in Polyomics to diseases associated with the world’s poorest people.

Whats the most frequently asked question about your work?

“Can you really do that?”

The mass spectrometry based approach to untargeted metabolomics reveals the relative quantities of hundreds or even thousands of individual metabolites in a given system in just a single experiment.

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

“Is 2030 a realistic target for the elimination of sleeping sickness?”

The gains made against trypanosomiasis have been incredible in the twenty first Century. However, the end games for other infectious diseases, like polio and Guinea worm, show how difficult elimination can be. Yet we are already witnessing funding agencies turning their backs on the disease when confronted with choices on where to put their resource.

Trypanosoma brucei metabolic network present at the trypanocyc database

Trypanosoma brucei metabolic network , present at the trypanocyc database

Tell us something about you that might surprise us…

I climbed Mont Ventoux as the last of a series of high mountains in France by bicycle this summer. (I’ve always loved sport although my contemporary physique offers few clues to this!).

What keeps you awake at night?

Excitement about a new discovery and its meaning can keep me awake with an energised buzz. Worries about deadlines, sustainability targets and the like can keep me awake in a less energised state too.

Whats the best piece of advice youve been given? 

Decide what it is you want to do and pursue that irrespective of what others tell you about its worth.

The chain-reaction question, set by our previous spotlighted researcher Dr Faith Osier, is: What makes you really happy about your work and research?

Finding something new and of obvious impact and then validating the finding. Such discoveries are happening at an accelerated rate in Glasgow Polyomics, and telling our partners that they appear to have a really significant observation in their data is hugely gratifying.

You can find out more about Professor Mike Barrett’s work on his University of Glasgow researcher page and by visiting the Glasgow Polyomics website.

 

Image of the Week: Dissection

5 Sep, 2014

L0057749 Part of a human stomach dissected by Edward Jenner, England,

This week’s image of the week is interesting for a number of reasons. At first glance, it looks like a delicate antique fan that might keep you cool in the heat of summer, but in reality it is something entirely different.

What you’re actually seeing here is a thin section of a human stomach, which has been flattened and injected with wax. This technique was used to show the veins, arteries and delicate membrane of the stomach wall, which wouldn’t be so easily identifiable without wax.

This specimen dates back to between 1790 and 1823, and the other interesting fact is that it was prepared by Edward Jenner, more commonly known for his pioneering work on vaccination.

Thought of by many as ‘the father of immunology’, Jenner’s work helped lead to the eradication of smallpox. He was also known for his delicate dissections, which were an important part of medical education, due to a lack of bodies that could be used to show students the workings of the human body.

The specimen above may have been used as a teaching aid to show the structure of the stomach.

Image credit: Science Museum, London, Wellcome Images

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

Getting passionate about primary science

4 Sep, 2014

One of the key priorities for the Wellcome Trust Education and Learning team is reinvigorating primary school science. We know that early encounters with science and discovery help to shape children’s understanding of the world and develop important skills. A recent Wellcome Trust study showed that some schools were missing out on access to specialist science expertise. Irchester Community Primary School, which was involved in the study, has taken an innovative approach providing a dedicated science space in the school and their very own scientist-in-residence, following the Lab-13 model. Wellcome Trust Primary Science Lead, Louise Stubberfield spoke to staff at Irchester, to find out how about their approach to science…

Scientist in residence

Jennifer Hogan, scientist-in-residence at Irchester Community Primary School

“It is so important that primary science is not a collection of facts to be learned, nor a set of limited predetermined fair-tests that are followed recipe-like to a known result. Real science is not like that!” says Tracy Tyrrell, science lead at Irchester Primary.

“I am passionate about science and it’s my job to make everyone else – the senior leadership team, teachers, children, parents and beyond – as enthused and excited about science as I am.

“Luckily, I have the help of our fabulous scientist-in-residence, Jennifer Hogan, and between us we manage to keep up-to-date with key developments in science and science pedagogy via Association for Science Education events, Twitter, STEMnet, etc. We trawl the internet and continuing professional development (CPD) sessions for innovative and inspiring activities and run staff training, whole-school events, community events and more in order to show everyone that science is remarkable, attention-grabbing, thought-provoking, motivating and fun.”

Primary science one“We are all familiar with little ones asking “Why?”, “What’s that for?” and “What happens if…?” says scientist-in-residence Jennifer Hogan. “Our approach actively encourages and promotes this questioning and innate interest, to drive further investigation and encourage them to think like real scientists.”

“We passionately believe that science is curiosity driven, and children in our lab lead their own learning” she says. Jennifer has been the scientist-in-residence at Irchester for the past three years – after facing her future students on an interview panel.

“One of the unique elements of the Lab_13 model is that it is managed by a committee of eight 9-11 year olds”, she explains. “These children have responsibility for the day-to-day running of the lab and have control over all the decisions associated with that space.

“This allows them to build up their confidence and develop a wide range of skills and one of their first jobs as a committee was writing the job description, and conducting the interviews for the Scientist-in-residence post. Scary!”

The aim is to incorporate as much practical experimentation as possible, allowing the children to really “do” science and use real scientific equipment, giving them ownership of their investigations and allowing them to find out answers to questions for themselves.

Petri girl“Our children lead from what they know and what they want to know, and the science lessons are tailored to their needs, abilities and interests” says Tracy. “They are able ask questions, plan their own investigations and ponder over results – drawing sensible conclusions or raising further questions.

“Spurred on by the success of the lab, curiosity is actively encouraged and celebrated in every class, and children’s questions form the basis of science planning across the school.

“We are not teaching children science, but teaching them how to be scientists” she explains. “It is an approach to learning that questions rather than accepts. It promotes critical and logical thinking with an open mind.

“How else will we create adults capable of furthering our understanding of our world and improving our lives?”

Jennifer says that being a scientist-in-residence is a hugely exciting and rewarding role. “All our investigations begin with a child’s question.

“My role is to guide them towards posing scientific questions and advise on the planning and conducting of investigations in the lab. This leads to wide range of subjects being covered on a day-to-day basis.”

microscope kidBut what do the children make of it? One boy who had been part of the Lab_13 Management Committee sums it up nicely: “The best thing about Lab_13 is now I know that, in science, sometimes “I don’t know” IS the right answer”.

Irchester primary school clearly makes the best use of its science expertise. But since there are few teachers who have specialised science knowledge, not all schools are so lucky.

In a recent Wellcome Trust survey, headteachers told us that the single action that would make a difference is ensuring that teachers can access high quality science CPD, but that action was, sadly, rarely prioritised. It’s vital then that the UK champions primary science as we recommend in our report.

 

You can access the full Wellcome Trust report, The Deployment of Science and Maths Leaders in Primary Schools on our website, where you can also read a summary of our recommendations based upon the findings.

How to Succeed at Open Innovation

3 Sep, 2014

Open innovation

Today we launchShaping the Future of Open Innovation: A practical guide for life sciences organisations”, a new resource created by a collaboration led by the Wellcome Trust, the Centre for the Advancement of Sustainable Medical Innovation (CASMI) and Kinapse. Rosie Pigott from CASMI, a Wellcome Trust seed funded initiative to accelerate the process of medical translation from bench to bedside, shares her top tips on open innovation.

“No single group can solve all the problems in this space. We need to work together in partnership.” Dr Gustavo Stolovitzky, Director, DREAM Project

In this increasingly open, collaborative, problem-solving world, open innovation has rapidly become accepted as standard practice in many areas of life sciences. In creating this report, we explored a selection of open innovation models that have emerged over recent decades and collated the different experiences and lessons-learned from partners, to feed into a practical tool kit that we could share.

Our definition of what ‘open’ means in this context was fairly broad and we examined a wide range of open innovation ‘experiments’ – from academic–industry collaborations to crowdsourcing.

For this project, we defined open innovation as the process of innovating with others for shared risk and reward in order to create new products, processes or ideas that could not otherwise have been achieved alone, or enabling them to be achieved more quickly, cheaply or efficiently.

We interviewed a number of experts from diverse organisations, and it soon became clear that there is no one-size-fits-all model for succeeding at open innovation. Project partners need to be open-minded about one another’s cultures, capabilities and constraints, and must allow sufficient room to tailor a partnership model that takes these factors into account.

A number themes that came out of the discussions and we’ve created a list of the top 15 strategies for establishing a successful open innovation initiative.

Ensure clear definitions
Clearly define the opportunities and potential benefits and risks for partners from the start. It is also important to consider conflicts of interest for each partner. Establish what everyone understands ‘open’ to mean in the context of the project. Partners should ensure that a mutually agreed and clear understanding exists and that this is expressed in writing before proceeding.

Working_Together_Teamwork_Puzzle_ConceptAlign objectives
Ensure that you align all partners’ goals at the outset. Each party must unambiguously agree the objectives of the collaboration in writing, including any specific milestone targets to be achieved during the lifespan of the collaboration and what the ultimate outcomes should be. It may be that the objectives don’t align completely – at this point partners should consider whether a collaboration is really the most appropriate way to achieve their goals.

Be strategic
Don’t be opportunistic about engaging in open innovation. Only commit if it fits with strategic priorities and if the objectives are truly harmonised.

Clearly divide outputs
Think through what the outputs will be and how value will be distributed among partners throughout the project.

Appreciate partner expertise
Make the most of the diversity of experience and expertise within the partnership. Be sure to appreciate areas of knowledge and skill and commit quality resources.

Communicate, communicate, communicate!
Communication is key to maintaining openness and transparency, both internally and externally.

Don’t overlook issues of intellectual property (IP)
Set clear IP ownership policies and strategies establishing who will own any resulting IP rights and agree on what can be made public. Even in the most straightforward model where no IP will be claimed and all results are released to the public domain, the IP policy should be expressly and clearly agreed between the parties at the outset. 

Define commercial benefit
Be clear about what the commercial benefit of the project could be, and how it will be captured and who by.

Create end-of-project guidelines
Be clear about what will happen at the end of the project. How will it wind-down? Who owns what?

Impartial environments
Have a neutral convener if this will facilitate decision-making.

Open minded

Find ‘open’-minded people
Invest in building the right team to manage projects and relationships effectively.

Define responsibilities
Clearly define the roles of each partner and understand that there are expectations for every side to contribute.

Evaluate
A robust review process will help to keep the project on track and define the points where go/no-go decisions need to be made.

Be flexible
Maintain a level of flexibility in budgeting and ways of working and have the ability to evolve.

Work together
Open innovation involves collaboration. Listening to one another and sharing ideas is important. Don’t just try to tell partners what to do!

The boundaries of open innovation are continually progressing. The demand for open access research outputs is also intensifying, and crowdfunding is a growing phenomenon in the life sciences sector. We are moving towards a more open world, which organisations must engage in to survive. As social and economic pressures make the healthcare landscape more demanding for all, open innovation represents a major tool for the creation of a more productive and sustainable ecosystem.

Author Rosie Pigott works at CASMI, you can find out more about their work on their website, and read the full report Shaping the Future of Open Innovation: A practical guide for life sciences organisations.

Image credits: Working together – Lumaxart – CC-BY-SA, Open minded – Thinkpublic on Flickr –  CC-BY-ND

Wellcome Trust Research Round-up: 1/9/14

1 Sep, 2014

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

Genes linked to development of glaucoma

N0022146 Testing for GlaucomaA new study funded by the Wellcome Trust and Fight for Sight has identified four new gene locations associated with glaucoma, an eye condition that can lead to blindness and visual impairment. It is hoped the finding could lead to earlier diagnosis and new therapies for treating the condition.

Glaucoma is the leading cause of irreversible blindness in the world. It is caused by damage to the optic nerve, usually due to the eye pressure inside the eye (intraocular pressure) being too high because eye fluid does not drain properly.

In the study published in Nature Genetics, researchers carried out a meta-analysis of more than 35,000 people from seven countries, including subjects of Asian and European descent, with data drawn from the International Glaucoma Genetics Consortium (IGGC).

A site on the ABO gene, which determines blood group, is one of the locations identified, and higher eye pressure appears to be linked to blood group B.

The study also found that a genetic change in the ABCA1 gene is associated with an increased risk of developing both high inner eye pressure and glaucoma. ABCA1 is a major regulator of cellular cholesterol and lipid levels, although further research is required to understand how this mechanism works in the eye.

Early diagnosis of glaucoma is crucial because if it is treated early enough, damage to vision can be prevented. In future it may be possible to provide intensive screening to those identified as being at higher genetic risk.

Professor Chris Hammond from the Department of Twin Research and Genetic Epidemiology at King’s College London, who directed the study, said: “Although eye drops are already available to treat glaucoma, these are not always effective. These findings help us to understand why some people get glaucoma and explain why the condition tends to run in families.”

Male fruit flies’ chemical demand for monogamy

fly sexA new study in The Journal of Cell Biology provides an insight into how male fruit flies

improve their reproductive success by stopping females from mating with other flies.

In addition to sperm, semen carries products that foster sperm survival, promote egg fertilization, and serve other functions that optimise a male’s chances of passing along his genes.

In male fruit flies’, reproductive accessory glands (thought to be equivalent to the prostate gland in humans) secrete signalling chemicals into the seminal fluid that make the recipient females less inclined to mate again with other flies.

But it’s unclear how some of these signalling chemicals are produced and delivered in order to reprogram a female’s behaviour against her own self-interest. Researchers funded by the Wellcome Trust have identified tiny membrane-bound vesicles called exosomes that are secreted into the seminal fluid by the so-called “secondary cells” of male accessory glands.

The authors showed that, after mating, the exosomes fuse with sperm and interact with cells along the female reproductive tract.

When the researchers reduced the number of exosomes produced by secondary cells, the female flies were more inclined to re-mate. This indicates that the exosomes are responsible for the behavioural changes, by interacting with the targeted female cells to overpower normal signalling pathways.

Puberty in girls influenced by one parent more than the other

AS0000131F03 Teenage girlsThe age at which girls reach sexual maturity is influenced by ‘imprinted’ genes, a small sub-set of genes whose activity differs depending on which parent passes on that gene, according to new research published today in the journal Nature.

The findings come from an international study of more than 180,000 women involving scientists from 166 institutions worldwide. The researchers identified 123 genetic variations that were associated with the timing of when girls experienced their first menstrual cycle, by analysing the DNA of 182,416 women of European descent from 57 studies. Six of these variants were found to be clustered within imprinted regions of the genome.

Lead author Dr John Perry, a Henry Wellcome Postdoctoral Fellow at the University of Cambridge said, “Normally, our inherited physical characteristics reflect a roughly average combination of our parents’ genomes, but imprinted genes place unequal weight on the influence of either the mother’s or the father’s genes. Our findings imply that in a family, one parent may more profoundly affect puberty timing in their daughters than the other parent.”

The activity of imprinted genes differs depending on which parent the gene is inherited from – some genes are only active when inherited from the mother, others are only active when inherited from the father. Both types of imprinted genes were identified as determining puberty timing in girls, indicating a possible biological conflict between the parents over their child’s rate of development.

Further evidence for the parental imbalance in inheritance patterns was obtained by analysing the association between these imprinted genes and timing of puberty in a study of over 35,000 women in Iceland, for whom detailed information on their family trees were available.

In other news…

Congratulations to Professor Rob Klose who has been awarded the Royal Society Francis Crick Lecture for his research into how chromatin-based, and epigenetic processes, contribute to gene regulation. Professor Klose has been supported throughout his career by the Wellcome Trust, beginning with his PhD studentship.

Another Wellcome Trust-funded PhD student, Dr Jenny Bangham, has won the Marc-Auguste Pictet Prize for her dissertation “Blood groups and the rise of human genetics in mid-twentieth century Britain”. The prize is given out every other year by the Société de Physique et d’Histoire Naturelle de Genève on a different theme pertaining to the history of science.

Image credits: Testing for Glaucoma – Libby Welch, Wellcome Images, Drosophila melanogaster mating – ImageEditor on Flickr, CC-BY 2.0, Teenage girls – Anthea Sieveking , Wellcome Images

Image of the week: Ebola

29 Aug, 2014

L0076142 Ebola. Sculpture by Luke Jerram, c. 2004

This week’s image is of a sculpture of the Ebola virus, created by artist Luke Jerram.

It is an unusual, and artistic, take on Ebola. With the virus continuing to spread in West Africa and the responses from the global health community regularly in the news, we’ve found that journalists and health writers have been requesting images of the virus, but they are not easy to come by.

Made entirely of glass, Luke’s sculpture is approximately one million times larger than the virus itself, and is part of a series of similar glass-works called Glass Microbiology.

All the pieces in this series are transparent and colourless, in deliberate contrast to artificially coloured scientific images. Being smaller than the wavelength of light, viruses in fact have no colour. To create the series, Luke worked in consultation with virologists from the University of Bristol, and photographs of his work have been used in medical journals, media stories, and one has even appeared on the front cover of Nature.

Not only is this a precise visual representation of Ebola, its jewel-like finish carries great beauty. This complex tension between the beauty of an object and what it represents lies at the heart of Luke’s sculptures, which have been created as a means of contemplating the global impact of disease.

This particular artwork was commissioned by a museum in Holland last year, but will be on display in the redeveloped Reading Room at Wellcome Collection in 2015.

Image Credit: Luke Jerram

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