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Image of the Week: Structure of the dynactin complex

27 Mar, 2015
Structure of the dynactin complex

Image courtesy of Urnavicus et al, made by Janet Iwasa (University of Utah)

This image shows a model of a tiny protein machine that moves things around within our cells. A new study reveals how the motor called dynein (grey) is attached to its cargo via an adaptor protein (orange). The attachment requires the help of another protein complex called dynactin (multi-coloured).

The dynein/dynactin machine drags its cargo along tracks called microtubules that stretch throughout the cell (a short section of microtubule is shown in green in the bottom left of the image). It takes things from where they are made to where they are needed.

When things go wrong with the dynein machinery it can result in neurodegenerative diseases such as motor neuron diseases, dementias or a form of Parkinson’s disease.  This intracellular transport mechanism can also be commandeered by viruses, such as those that cause herpes, cold sores, chicken pox and shingles.

A Wellcome Trust funded team of researchers, led by Dr Andrew Carter at the MRC Lab of Molecular Biology in Cambridge, have used a state of the art cryo-electron microscope to determine the structure of dynactin and show how it helps dynein bind to the cargo adaptor Bicaudal-D2.  Examples of the high-resolution cryo-electron microscopy maps are shown in the background of the image.

A great mystery in the field of cellular transport is why dynein requires dynactin. Carter and his team have revealed for the first time that they both form an intricate complex with the cargo adaptor sandwiched between them. This suggests dynactin acts as an “on switch” that activates dynein to move for long distances along microtubules.

The team expects that each different cargo, for example mitochondria, mRNAs, toxic aggregated proteins and different small transport vesicles, will have different adaptors. Future work will focus on whether they all bind in the same way as Bicaudal-D2, how dynein defects cause neurodegenerative diseases and whether it is possible to block it from carrying viruses.

The team’s research is the cover story on this week’s Science, and you can read the full paper online. To find out more about Dr Carter’s work, visit his website.

World TB Day: what next for prevention and treatment?

24 Mar, 2015

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TB remains a global problem with 1.5 million deaths and 9 million cases per year. On World TB Day, Wellcome Trust Senior Science Portfolio Developer Marta Tufet looks back at the history of TB prevention and treatment, explains what the Wellcome Trust is doing to support research in this area, and asks what more needs to be done to make an impact on this stubborn disease…

At 13 I moved to France mid-school term and mid-TB vaccination campaign. All the kids were lined up at the school’s gym and one by one a nurse inserted a needle into our forearms – the Tuberculin skin test to see whether we would mount a localised immune response, an indication that there had been exposure to the bacteria. To this day the memory remains vivid – not speaking a word of French at the time, it presented an excellent communication opportunity. I eagerly held out my arm and gestured other kids to do the same and compare who had the biggest reaction. To my surprise, I had nothing to show for it. A few days later, my newfound friends and I – those of us with still no lump on our forearms – were lined up again at the gym, and this time given the Bacille Calmette-Guerin (BCG) Vaccination, developed in the 1920s, with the aim of protecting us against the most serious form of TB.

BCG vaccination was mandatory for school children in France between 1950 and 2007, before a shift to selective vaccination. Similarly, the UK ran a universal immunisation campaign from 1953-2005. Today the WHO recommends that BCG be given to all children born in countries with a high prevalence of TB. But despite these multiple vaccination campaigns TB remains a global problem with 1.5 million deaths and 9 million cases per year.

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Marta (centre, wearing a yellow dress) at school in France where she received her BCG vaccination. 

Unfortunately, it would seem that for the past 90 years we have been relying on a vaccine that is far from perfect. Although BCG can protect against the severe extrapulmonary form of TB in children, it is unreliable in protecting against pulmonary TB, which accounts for the majority of TB cases globally. Moreover, BCG’s efficacy diminishes the closer you live to the equator, where TB is most prevalent. The vaccine is also not safe in infants who are infected with HIV, yet HIV is considered the single most important factor in the increase of TB in many countries, increasing the likelihood of a TB infection turning into active disease.

Because of these problems, we need a new more effective vaccine, which is easier said than done.  The complexities of TB disease, comprising both latent (without symptoms) and active states, the lack of adequate animal models, limited financial resources and poor coordination are just some of the contributing factors for why we are not any closer to a modern TB vaccine now than we were 15 years ago.

Most vaccine efforts have focused on the same model of understanding TB immunology as was used to develop the BCG vaccine. However, even the most promising TB vaccine to date, MVA85A, has failed to demonstrate significant efficacy in clinical trials. Since then, many researchers and funders feel the need to go back to the drawing-board to re-evaluate our understanding of what constitutes an essential and sufficient immune response to TB before pursuing new vaccine efforts.

Prevention aside, TB is in fact treatable with a mixture of antibiotics over a duration of 6-9 months. Regrettably, access to drugs in poorer countries is still an obstacle and detecting TB in the first place is not easy. Furthermore, these drugs are now threatened by the emergence of resistance. We can blame poor adherence to courses of treatment, falsified or poor quality drugs, or even the bacteria’s evolutionary prowess, but the reality remains strikingly worrying: in 2013 alone, 480,000 people developed multi-drug resistant TB, and for these individuals there is unfortunately little hope.

Today on world TB day we are being asked to “gear up to end TB” and at the Trust we are committed to support research towards this aim. Putting an end to TB will require more than our traditional investments in basic research towards vaccine and drug development.

To address this, the Welcome Trust, in partnership with the Medical Research Council (MRC) and the Department For International Development (DFID), have also been supporting a number of global health trials tackling multiple angles: from improved diagnosis, to optimized treatment regimens, to socioeconomic interventions:

  • The STAMP trial led by Stephen Lawn at the London School of Hygiene and Tropical Medicine (LSHTM) aims to improve treatment in patients with HIV and TB by determining whether the addition of a new urine-based test to the standard diagnosis strategy can reduce mortality in Malawi and South Africa.
  • The TRUNCATE-TB trial led by Patrick Phillips at University College London (UCL) aims to determine whether treatment for drug-sensitive TB can be improved whilst at the same time reducing the drive towards new cases of multi-drug resistant TB in multiple Asian countries by optimizing regimens at the individual level.
  • The TB fast-track trial led by Alison Grant at LSHTM aims to see whether you can reduce early mortality by using point-of-care technology to rapidly identify individuals presenting for HIV treatment at high risk of TB and ensuring they start TB treatment.
  • Diana Gibb at the MRC clinical trials unit is investigating whether a shorter treatment for children with milder forms TB is just as effective as the currently recommended treatment, which has been largely based on research conducted only in adults. This would not only be advantageous for the child but also for the over-burdened health systems, reducing the number of clinic visits children would need to make to take their drugs.
  • Carlton Evans at Imperial College is evaluating the impact of socioeconomic interventions for reducing poverty, improving access to TB care and consequently reducing the risk of future TB in Peru.

On top of this research, we also need new strategies to reduce the reservoir of latently infected individuals, from which new cases can arise. Current diagnostic tests cannot predict who will develop active disease, and in any case the current treatment options available are not adequate given the scale of the intervention that would be required – a third of the world’s population is currently predicted to be latently infected with TB.

20 years after my BCG vaccination, I was again tested for TB on moving to Seattle. I waved my arm again in front of my American colleagues and this time it was clear that I had the largest skin reaction from the Tuberculin test, a testimony to my BCG vaccination status (the US has never used mass immunization of BCG, relying instead on the detection and treatment of TB instead). A subsequent test, not affected by vaccination status, also came back positive. As I was not showing any signs of active disease it was concluded that between 1994-2014 I had most likely been exposed to TB. The risk of this progressing to full blown disease is about 5-10%. It would seem I have now joined a third of the world’s population in harbouring latent TB.

More information about World TB Day can be found here

Image credit: NIAID, Mycobacterium tuberculosis Bacteria, the Cause of TB on Flickr

Ebola One Year On: a Wellcome Trust Research Round-Up Special

23 Mar, 2015

B0009931 Ebola virus structure, illustration

A year ago today (23 March 2014), the World Health Organization confirmed what many in the global health community had already feared. An outbreak of a deadly haemorrhagic fever that had emerged a few months earlier in Guinea was caused by the Ebola virus. What followed was an epidemic on a previously unimaginable scale, which to date has claimed at least 10,000 lives.

Over the past year, people across the Wellcome Trust have helped to catalyse an unprecedented global response to the outbreak. In many cases this has involved condensing processes that normally would take years of painstaking work into a matter of months.

Our emergency Ebola funding package has now awarded around £11.6 m to research aimed at identifying clinical and public health interventions that could save lives in this, and future outbreaks of Ebola. In this special edition of Research Round-up, we take a look at progress so far.

Since August 2014, the Trust has been working with scientists, industry, governments and agencies around the globe to fast-track the development of two promising Ebola vaccines: Merck’s rVSV-EBOV and GlaxoSmithKline’s ChAd3 (chimp adenovirus type 3).

Vaccines

Support from the Trust has enabled researchers to rapidly set up human trials of these two promising vaccines, first in healthy volunteers to make sure they were safe followed by large-scale efficacy trials of both vaccines, which are now underway in West Africa.

A ring-vaccination trial of rVSV-EBOV started last month in Guinea, and it’s possible that this will be expanded in the coming weeks to incluEbola vaccinede trials of ChAd3 with a ‘boost’ from a different type of vaccine called MVA (developed by Emergent). Initial results from the trial are expected in the second half of 2015 and there’s still a chance that this work could have an impact on the current epidemic, if one or more of the promising vaccines turns is effective at preventing transmission.

Treatments

Vaccines are the most effective way of protecting individuals and communities against the spread of infectious disease, but there is also an urgent need to develop effective treatments for Ebola.  We set up a £3.2 million treatment platform in September 2014 to help fast-track this process.

The first study set up through this platform, a trial of an antiviral called brincidofovir, unfortunately had to be stopped shortly after it began because of the dramatic decline in new Ebola infections at the study site in Liberia. But Professor Peter Horby and his team at the University of Oxford have now started a second trial of another promising drug called TKM-Ebola. By concentrating their efforts in Sierra Leone, where cases remain high, they will have the best possible chance of finding out whether any of the candidate treatments can stop people dying from Ebola. This approach will also hopefully help to develop protocols to allow clinical trials to be rapidly set-up in similar emergency situations in the future.

Cambridge-based biopharmaceutical company Kymab and Public Health England scientists are also working here in the UK to identify further promising treatment options.

Surveillance and modelling

Understanding how and why infection spreads is a crucial part of any epidemic response. Two projects funded through the Research for Health in Humanitarian Crises (R2HC) programme are working towards this goal. The first, led by the London School of Hygiene & Tropical Medicine, is tracking changes in the spread of the disease in West Africa and evaluating the impact of measures put in place to control the epidemic. As second project at Oxford University is trying to predict the trajectory of the outbreak and produce maps to help the WHO and other agencies in planning their response.

Prevention

It’s likely that many lives have been saved in the present epidemic through basic public-health measures alone. Isolating suspected cases early and encouraging people to seek treatment are key to this process, but this can prove challenging in communities where there is no established system of healthcare. Researchers from Umea University in Sweden have been working on a social marketing strategy with the goal of developing tailored public health messages specific to the cultural and societal context of this epidemic.Ian gf

Another key element of preventing the spread of Ebola in the present outbreak has been the widespread use of personal protective equipment. A team from International Rescue Committee UK is devising strategies to make sure health workers stick to the strict protocols for wearing and removing the equipment that are required for it to be effective.

Diagnostics

One of the challenges facing health workers in the three Ebola-affected countries has been the difficulty in quickly establishing a diagnosis, as symptoms of the early stages of infection are shared with many common diseases. Two diagnostic tests being developed with R2HC funding could revolutionise this process by delivering a rapid point-of-care diagnostic test for Ebola. One is developing a device to test for Ebola virus in saliva, while a second will create a solar-powered mobile suitcase laboratory capable of confirming a diagnosis within 15 minutes.

Societal factors

In the early stages of the epidemic, it is likely that certain cultural practices, such as preparing the bodies of victims for funerals when they are still highly infectious, contributed to the spread of the disease. Changing these practices requires a thorough understanding of the society in which the outbreak is taking place. The London School of Hygiene & Tropical Medicine has set up an anthropology platform to provide clear, practical, real-time advice about how to engage with crucial socio-cultural and political dimensions of the outbreak, and how best to build locally-appropriate interventions.

To find out more about the Wellcome Trust’s Ebola rapid-response research fund visit our Ebola funding page, or view  our previous post on What the Wellcome Trust is doing to tackle Ebola

Ebola: One Year On

20 Mar, 2015

C0105595 Dr Felicity Hartnell. Ebola vaccine trial

A year on from the first confirmed case of Ebola, nearly 25,000 people have been infected with the disease. Although the epidemic appears to be slowing down and trials into potential treatments have begun, there are many lessons still to be learnt about our ability to prepare for and respond to epidemics. Director of the Wellcome Trust, Dr Jeremy Farrar, and Seth Berkley, CEO of Gavi, look back over the events of the past year in this opinion piece that originally appeared in the Wall Street Journal on 18th March 2015.

One year ago Monday, scientists confirmed that the cause of a deadly fever in Guinea, which had already killed 59 people and was continuing to spread, was the Ebola virus. Twelve months later, trials for a second promising vaccine have begun in Guinea, with a first trial already underway in Liberia. But this progress doesn’t mean that the Ebola crisis has been solved or that we’re better prepared for future epidemics yet.

The best news is that the epidemic is coming under control. In the week to March 8, 116 new cases were reported from Sierra Leone and Guinea, compared to a thousand or more per week at the height of the outbreak. Liberia reported no new confirmed cases for the second consecutive week. This reduction is mainly thanks to the implementation of basic hygiene and public-health procedures: the rehydration of patients; the separation of the healthy from the sick, the dying and the dead; the use of diluted bleach for washing; and a better understanding of cultural practices so that families and communities can be protected from the risk of, for example, preparing dead bodies for funerals when they are still highly infectious.

Yet applying higher-tech solutions, such as a vaccine, has been much slower going. Several Ebola vaccines were first conceived more than a decade ago but then shelved. Much more could and should have been done in advance of this outbreak, measures that would have enabled trials to begin as soon as the alarm was raised. Critical safety and dosing studies could have been carried out years ago rather than waiting until an outbreak occurred.

The medical-research, pharmaceutical and global-health communities have hardly dragged their heels as the past year’s epidemic progressed, nor did affected governments, donor governments and private philanthropists. But efforts to develop a vaccine were dogged by a lack of consensus on whether clinical trials were necessary or appropriate in an epidemic context. And when agreement was finally reached, trials took too long to get started. A lack of agreement over trial protocols caused further delays.

As a result, no trial was ready to go until the beginning of 2015, and some still have not started. Procedural hurdles are there for good reasons, primarily safety. But delays in this case have likely cost lives and certainly jeopardized trials, which require large numbers of participants. Ebola cases are thankfully now in decline, but one study—of the drug brincidofovir—has already collapsed as a result.

The problem with diseases like Ebola, which kill ferociously but occur only sporadically, is that there is simply no market for related medical interventions. There are usually only a few hundred cases every few years, and typically in poor African countries. Companies would unlikely see any return on the substantial investment required to get a drug or vaccine through trials. The current trials are happening only because manufacturers, philanthropists and donor governments agreed to share the costs. Who will pay for the administration of each dose, if they are approved, remains unclear.

Until we can develop some way to fund research and development related to likely future epidemics and test new drugs and vaccines swiftly during epidemics, we will remain vulnerable to outbreaks. We need to stop waiting until we see evidence of an infectious disease becoming a global threat before we treat it like one.

The medical and scientific community needs to continue identifying other potential disease threats, and develop the necessary tools to estimate how big a risk they pose. There are probably more than a dozen known diseases, including other haemorrhagic fevers like Marburg and Lassa fever, or henipavirus, for which markets are unlikely to ever exist but which could cause Ebola-style crises in the future. There is already modelling to identify the most significant threats: Risk factors include diseases caused by RNA viruses, and diseases that are endemic in animal populations, especially when these have close contact with humans.

We also need further research into the biology of such diseases. Understanding their genetic sequences, their animal hosts and their mode of transmission—from animals to humans and then from human to human—can make it easier to spot and counter epidemic threats sooner. Areas of focus must include these diseases’ interactions with the immune system, and identifying biological signatures that indicate greater transmissibility or virulence.

Public-health authorities need to consider now how best to test drugs and vaccines safely and quickly once the next outbreak occurs. Not only do delays deprive patients of potentially life-saving treatments, they also deny scientists the chance to observe the efficacy of treatments at the height of an epidemic.

Finally, we need to invest in better surveillance to spot patterns in future outbreaks sooner. This Ebola outbreak has differed from previous occurrences not because the pathogen itself has changed but because of the environment in which it emerged. For the first time, Ebola spread in more populated and urban areas, which enabled it to infect and kill more people faster than ever before. Preventing similar outbreaks in the future means identifying such new factors earlier and reacting more quickly.

One year on, this outbreak may now appear to be subsiding. But there will be other epidemics, including Ebola itself. We can’t afford not to learn the lessons of this one.

Image of the Week: Genetic map of the British Isles

20 Mar, 2015
Image courtesy of Stephen Leslie et al and Nature

Image courtesy of Stephen Leslie et al and Nature

Legend: Map of the UK showing clustering of individuals based on genetics, and its striking relationship with geography. Each of the genetic clusters is represented by a different symbol (combining shape and colour, with legend at the sides). There is one symbol plotted on the map for each of the individuals in the study. The ellipses give a sense of the geographical range of each genetic cluster.

A landmark new study into the genetic makeup of the UK has revealed that there may be scientific evidence underpinning those local ties that so many of us feel. This colourful map of the British Isles shows the genetic clusters that exist across the country, and how in many cases, local populations share a similar genetic makeup.

Researchers from the People of the British Isles project, supported by the Wellcome Trust, used DNA samples from 2,000 people, all of whose grandparents were born within 80km of each other, resulting in a map of the genetic makeup of late 19th century Britain.

Among the findings is the intriguing discovery that sometimes a geographic or political boundary can also correspond to a distinct genetic boundary. In Devon and Cornwall the map shows a clear distinction between the genetic makeups of the two counties, with a separate cluster present either side of the modern county boundary.

Samples taken from Wales show that the Welsh are the most similar to the earliest settlers of the British Isles, but also that the three defined genetic clusters exist in the North and South of the country as well as along the border with England.

Orkney also emerged as the most genetically distinct from the rest of the UK with 25% of DNA from Norse ancestry – perhaps unsurprising given its history of Norwegian rule.

In total 17 distinct clusters were identified across the UK. Along with an understanding of the historical migrations into Britain, the researchers used a further 6,000 samples from modern day Europe to help explain how these genetic clusters may have emerged.

You can find out more about People of the British Isles on the project website and the full study was published this week in Nature.

 

Wellcome Image Awards 2015 Winners

18 Mar, 2015

WI-6070.31 WIA15_holding slide

“Fascinating, sad, macabre… also delicate, detailed and beautiful” – just some of the words used to describe the overall winner in the Wellcome Image Awards 2015. Announced at at ceremony at Wellcome Trust HQ this evening, Michael Frank’s image of a pregnant pony’s uterus took the top prize. Here we share the full collection of winning images…

“As far as standout images go, the image of the horse’s uterus with the fetus still inside was incredible, and just sticks in my mind,” said James Cutmore, Picture Editor of BBC Focus magazine and one of the judges of this year’s awards. “It evokes many different emotions at once.”

Pregnant pony uterus – Michael Frank, Royal Veterinary College

Pregnant pony uterus - Michael Frank, Royal Veterinary College

Pregnant pony uterus – Michael Frank, Royal Veterinary College

The photograph shows the uterus of a pregnant New Forest pony. Approximately five months into the pregnancy, the developing pony is outside the uterus, but remains attached by its membranes and umbilical cord. This is a historical specimen from a culled animal that happened to be pregnant at the time. It is preserved in formalin at the Anatomy Museum of the Royal Veterinary College.

Goat stomach chamber – Michael Frank, Royal Veterinary College

Goat stomach chamber - Michael Frank, Royal Veterinary College

Goat stomach chamber – Michael Frank, Royal Veterinary College

You may be aware that cows have a number of stomach chambers, but did you know the same is true for sheep and goats? This second winning image by Michael Frank shows the second of four stomach chambers (the reticulum) of a goat. The inside of the reticulum forms a honeycomb pattern, which is home to the bacteria that help break down food.

Boll weevil – Daniel Kariko

Boll weevil - Daniel Kariko

Boll weevil – Daniel Kariko

Looking like something you might expect in a Star Wars film, this image shows the head of a boll weevil under a scanning electron microscope. The boll weevil has a long curved snout, but don’t be deceived by the apparent friendly demeanour in this portrait – boll weevils can destroy entire cotton crops, despite only being 6-8 mm long .

Immune cell detects disease – N Dieckmann and N Lawrence, University of Cambridge

Immune cell detects disease - N Dieckmann and N Lawrence, University of Cambridge

Immune cell detects disease – N Dieckmann and N Lawrence, University of Cambridge

This super-resolution micrograph shows a natural killer cell (left) examining a second cell for signs of disease (right). Natural killer cells are part of the immune system and can recognise and destroy infected or cancerous cells by releasing toxic chemicals that cause them to self-destruct.

Cat tongue – David Linstead

Cat tongue - David Linstead

Cat tongue – David Linstead

Have you ever been licked by a cat? Then you’ll be familiar with the rough sandpaper texture of cats’ tongues. This polarised light micrograph shows a cross-section through part of a cat’s tongue – with the round bumps (papillae) that are responsible for that scratchy texture visible. The photographer, a retired scientist, exercises his passion for microscopy by looking at classic Victorian slides (such as this sample) with a new perspective.

Tuatara skeleton – Sophie Regnault

Tuatara skeleton - Sophie Regnault

Tuatara skeleton – Sophie Regnault

This micro-CT scan shows the skull and front legs of a tuatara – a rare species of reptile found only on certain offshore islands of New Zealand. These mid-sized reptiles are all that is left of an ancient group of animals that shared the Earth with the dinosaurs. These creatures get their name from the Maori word meaning ‘spiny back’, reflecting the presence of spines along the animal’s neck, back and tail.

Curvature of the spine – Mark Bartley, Cambridge University Hospitals NHS Foundation Trust

Curvature of the spine - Mark Bartley, Cambridge University Hospitals NHS Foundation Trust

Curvature of the spine – Mark Bartley, Cambridge University Hospitals NHS Foundation Trust

Are you sitting comfortably? How is your posture? This photograph of a 79-year-old woman’s back shows an abnormally curved spine. Known as kyphosis, or ‘dowager’s hump’, the upper back and shoulders are rounded forwards. Although kyphosis can occur at any age, it is most commonly seen in elderly women and may be caused by a range of things including poor posture, injury, osteoporosis, cancer and cancer treatments, infection, a birth defect, and degenerative or endocrine diseases.

Delivering medicine to the lungs – Gregory Szeto, Adelaide Tovar and Jeffrey Wyckoff, Koch Institute, copyright MIT

Delivering medicine to the lungs - Gregory Szeto, Adelaide Tovar and Jeffrey Wyckoff, Koch Institute, copyright MIT

Delivering medicine to the lungs – Gregory Szeto, Adelaide Tovar and Jeffrey Wyckoff, Koch Institute, copyright MIT

This confocal micrograph shows microparticles (pink) on a set of mouse lungs. The microparticles can carry medicines, and are being studied to see whether they can deliver these drugs to the lungs. Current anticancer therapies have many toxic side-effects, so researchers hope that these microparticles could one day deliver anticancer medicine in a much simpler, more targeted way – for example, in an inhaler – with fewer side-effects.

3D-printed lungs in ribcage – Dave Farnham

http://www.wellcomeimageawards.org/2015/delivering-medicine-to-the-lungs

3D-printed lungs in ribcage – Dave Farnham

Photograph of 3D-printed human lungs inside their ribcage. This image shows a 3D-printed copy of the lungs and ribcage belonging to a patient called Caroline, diagnosed with Hodgkin lymphoma. Two-dimensional images from CT scans were converted into a 3D computer model by the artist, who was then able to print a 3D copy.

Mouse brain – Luis de la Torre-Ubieta, Geschwind Laboratory, UCLA

Mouse brain - Luis de la Torre-Ubieta, Geschwind Laboratory, UCLA

Mouse brain – Luis de la Torre-Ubieta, Geschwind Laboratory, UCLA

This micrograph of nerve cells inside a section of adult mouse brain wouldn’t look out of place on the wall of an art gallery. The brain has been sliced into thin sections, with one of the pieces seen here. After being sliced, it was chemically treated to make the tissue transparent so that structures deep inside could be more easily seen. This technique is being used to map the complex wiring of whole brains.

Mapping brain wiring – Dr Flavio Dell’Acqua

Mapping brain wiring - Dr Flavio Dell’Acqua

Mapping brain wiring – Dr Flavio Dell’Acqua

This picture shows bundles of nerve fibres inside a healthy adult living human brain, captured using magnetic resonance imaging (MRI). MRI was used to virtually slice the brain into left and right halves – the front of the head faces the left side of the image. Information on the network of connections was collected by a type of MRI (diffusion imaging) that tracks the movement of water molecules.

Fruit-fly nervous system – Albert Cardona, HHMI Janelia Research Campus

Fruit-fly nervous system - Albert Cardona, HHMI Janelia Research Campus

Fruit-fly nervous system – Albert Cardona, HHMI Janelia Research Campus

An organism’s nervous system controls everything it does, from breathing and moving to thinking and feeling. Reminiscent of a Jackson Pollock painting, this image shows part of the central nervous system of a fruit fly (D. melanogaster). Transmission electron micrographs were used to create a digital colour-coded map of the area.

Delivering medicine to the brain – Khuloud T Al-Jamal, Serene Tay and Michael Cicirko

Delivering medicine to the brain - Khuloud T Al-Jamal, Serene Tay and Michael Cicirko

Delivering medicine to the brain – Khuloud T Al-Jamal, Serene Tay and Michael Cicirko

A single brain cell (coloured green and pink) with a rectangular cut enabling observation of how tiny, nanometre-sized carbon nanotubes (coloured red and brown) interact with its surface. These nano-sized cylinders are made of carbon atoms, and are being researched for their ability to act as carriers to deliver drugs or genes to cells – for example, anticancer medicines to a tumour.

Old anatomy model – Anthony Edwards, St James’s Hospital, Dublin

Old anatomy model - Anthony Edwards, St James’s Hospital, Dublin

Old anatomy model – Anthony Edwards, St James’s Hospital, Dublin

Old anatomical models like these provide a way for people to look under the skin and see what’s below. Often used to educate students or explain medical procedures to patients, they have varying levels of detail – some have removable parts, to show how things fit together. This particular model was about to be thrown away when the photographer rescued it to take one last photograph to honour the service it had provided to medical students at Trinity College Dublin.

Children’s multi-sensory unit – Geraldine Thompson, Central Manchester University Hospitals NHS Foundation Trust

Children’s multi-sensory unit - Geraldine Thompson, Central Manchester University Hospitals NHS Foundation Trust

Children’s multi-sensory unit – Geraldine Thompson, Central Manchester University Hospitals NHS Foundation Trust

Photograph of an interactive multi-sensory unit used to distract and comfort anxious children receiving treatment in hospital. It can provide a relaxing environment while stimulating different senses. For example, patients can watch colours change in the bubble tube while touching the outside to feel it gently vibrate. Multi-sensory stimulation can also help people with learning disabilities, autism and dementia.

Chemical reactions in the kidney – Jefferson R Brown, Robert E Marc, Bryan W Jones, Glen Prusky and Nazia Alam

Chemical reactions in the kidney - Jefferson R Brown, Robert E Marc, Bryan W Jones, Glen Prusky and Nazia Alam

Chemical reactions in the kidney – Jefferson R Brown, Robert E Marc, Bryan W Jones, Glen Prusky and Nazia Alam

Colour-coded map of part of a mouse kidney as it metabolises food. Three small molecules – the amino acids aspartate and glutamine, and the antioxidant glutathione – produced by the metabolic processes are visible (coloured red, blue and green, respectively). The brighter the colour, the more of that molecule there is in the cell. This image was created using a technique called computational molecular phenotyping and shows how metabolism can vary between cells in the same organ at a given point in time.

Newly discovered parasitoid wasp – Andrew Polaszek, Natural History Museum

Newly discovered parasitoid wasp - Andrew Polaszek, Natural History Museum

Newly discovered parasitoid wasp – Andrew Polaszek, Natural History Museum

This image shows a new genus of parasitoid wasp that was recently discovered in the rainforests of Borneo – a single female wasp was found mixed in with thousands of other insects. This tiny parasitic wasp – only 0.75 mm in length – lays its eggs inside other insects, then after hatching, the larvae feed on their host, eating it alive from the inside out.

Pollen grains – Maurizio De Angelis

Illustration of pollen grains being released from a flower in the Asteraceae family – is one of the largest families of flowering plants – commonly known as the aster, daisy, sunflower or composite family. Pollen grains come in all shapes and sizes, but they are usually between 0.01 and 0.1 mm in size.

Greenfly eye – Kevin Mackenzie, University of Aberdeen

Greenfly eye - Kevin Mackenzie, University of Aberdeen

Greenfly eye – Kevin Mackenzie, University of Aberdeen

Not an octopus, but a scanning electron micrograph of a eye of a greenfly. Aphids have a pair of curved compound eyes that bulge out of the head and have a wide angle of view. These are made up of thousands of repeating units known as ‘ommatidia’, each with a tiny lens on the front surface, working together to produce a mosaic image. This allows the fly to see very quick movements, but not fine details or objects that are far away.

Purkinje cell – Professor M Häusser, Sarah Rieubland and Arnd Roth, UCL

Purkinje cell - Professor M Häusser, Sarah Rieubland and Arnd Roth, UCL

Purkinje cell – Professor M Häusser, Sarah Rieubland and Arnd Roth, UCL

This stunning image looks like coral, but is actually an electron micrograph of part of a particular type of nerve cell found in the brain called a Purkinje cell. The finger-like projections in this elaborate network act like tiny sensors, picking up information and passing on messages to help control and coordinate muscle movement. This one is from the cerebellar cortex of a rat brain, and in order to see the dendritic tree, the Purkinje cell was filled with a visual marker before being imaged.

If you want to get up close to these images, you can visit one of the exhibitions of the winners at 11 science centres, museums and galleries, around the country. From the Eden Project in Cornwall to Satrosphere in Aberdeen, and as far afield as the University of Texas Medical Branch in Galveston, USA – read more about this year’s participating venues on the image awards website.

 

Assessing the research potential of access to clinical trial data

17 Mar, 2015

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Access to the data generated by clinical trials is key to realising the full benefits of trials of new health interventions, and a valuable opportunity to generate new insights. There has been much recent discussion of how to maximise the impact of sharing of data from clinical trials, and with our track record of encouraging open access and data sharing, the Wellcome Trust is fully engaged with the issue. To help inform these discussions, we commissioned an independent study to look at research potential of increased access to trial data, and what mechanisms are needed to facilitate it. Will Greenacre, from the Wellcome Trust policy team, discusses the findings…

Clinical trials take place every day all over the world to test the safety and effectiveness of new medicines and other health interventions. Not only are trials central to the development of new treatments, but the data they generate can also be a valuable resource to others – both for testing the existing evidence, and for generating new insights to drive research.

However, while many researchers already share their data informally, there are few established mechanisms to enable data sharing on a larger global scale. Many datasets are not accessible to researchers who might want to analyse them, and in many cases researchers may not even know that data exists. The Wellcome Trust is keen to encourage transparency and data sharing in research. This has to be done in an effective and responsible way that benefits research, while also protecting the safety and privacy of participants.

Aim of the study

To help inform on-going discussions in the international research community around the development of new models for data sharing, the Wellcome Trust commissioned independent consultants Technopolis to carry out a study into the types of novel clinical research that are already being undertaken using data from existing trials, and to develop case studies and examples. We also asked them to look at the existing demand for access to data in the international research community, and what mechanisms are needed to enable more efficient sharing of data.

The project team carried out a survey of researchers, data managers, company representatives and others with an interest in data access, and followed this up with a series of interviews to explore the responses in more detail.

The results

The main findings were that data from existing trials is already helping to inform research in ways that are leading to tangible health benefits. This includes the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), which has used meta-analyses of clinical trial data to generate evidence on the efficacy of tamoxifen treatment for breast cancer, which has been adopted into guidelines for treatment of women with early breast cancer around the world.

They also found that enhanced access to trial data clearly has the potential to drive new clinical research in other directions, and that there is a real demand within the research community for access to data. This includes data from both academic and commercial clinical trials together  (70% of survey respondents cited this as ‘significantly important’ or ‘essential’).

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Key recommendations

There are some barriers to enhanced access, and the report sets out some recommendations for how to address them – with a particular focus on joining up existing data sharing initiatives. The recommendations are:

  • Link current data sharing initiatives and prevent further fragmentation of data landscape – through promoting establishment of larger data repositories and supporting linking of existing repositories and data portals
  • Establish a central information website, or consider adapting current clinical trial registries, with profiles and links to existing repositories and data portals to enhance discoverability
  • Establish a central repository or data portal to facilitate access to individual patient data from clinical trial data
  • Establish a global discussion forum of potential funders of individual patient data sharing initiatives to develop global support and a joined-up approach leading to the implementation of globally “linkable” repositories and data portals

The findings of this report are timely. In January the US Institute of Medicine (IoM) published a report of its study into strategies for the responsible sharing of clinical trial data (the Wellcome Trust was a sponsor of this work).

The Technopolis report ties in well with the IoM report’s conclusions, especially that a global consortium should be established to promote data sharing more broadly, and that we need to address the challenges involved. The study also provides useful data on what researchers think about data sharing, what barriers they would like to see addressed, and some directions for further work to inform new data sharing models.

We will be continuing discussions to take forward the report’s recommendations and to advance the data sharing agenda more broadly so that the full potential of clinical trial data to inform research can be realised.

You can read the Technopolis report in full on our website and find out more about the Trust’s role in taking forward efforts to increase access to clinical trial data.

 

Researcher Spotlight: Dr Julija Krupic

16 Mar, 2015

JK portrait pictureDr Julija Krupic developed a fascination with the way the brain maps the environment during her MRes. Since then she’s not looked back – securing a PhD with Prof John O’Keefe and a Sir Henry Wellcome Fellowship – she works at University College London, trying to discern the function of neurons in the hippocampus, with the hope that this may one day help us find a cure for Alzheimer’s disease. We asked her to tell us about her life in the lab, and what drives her research…

What are you working on?

I am studying the function of neurons in the hippocampal formation, a part of the brain’s limbic system. The hippocampal formation is crucial for spatial navigation, learning and memory. Damage to it results in impairments in spatial memory and various types of neurological and psychiatric disorders (e.g. Alzheimer’s disease, schizophrenia) as well as memory and learning problems associated with ageing.

There are four main classes of spatially tuned cells in the hippocampal formation: place cells – activated when the animal enters a specific area of the environment, grid cells – active in multiple places covering the entire environment and arranged in a symmetrical hexagonal pattern, head direction cells – active whenever the animal is facing a particular direction independent of the animal’s position, and finally, border cells – which fire whenever the animal is close to the borders of the environment.

cover with kandinsky for wellcomeUp till now my main focus has been on grid cells. I am interested in how grid cells acquire their hexagonal symmetry and how this symmetry is influenced by the environment’s geometry. Answering this question would lead us to understand the mechanism by which simple sensory information is converted into the perception of complex space.

What does your average day involve?

I am lucky to live close enough to UCL so that usually I walk to work in the morning. This gives me the opportunity to think about my current experiments, the best way to analyse the results and to generally plan my day.

A large part of my day is spent doing experiments or preparing for them (building various experimental setups and other bits and bobs, I love the tool development part of science – an endless playground!). My training as a physicist enables me to take part in the development of some of the new exciting tools in neuroscience. In addition to electrical recording as a way of studying neural activity we are now using lasers to record optically from hundreds of cells at the same time (as animals navigate in virtual environments.) We can begin to look at the way in which cells talk to each other and how networks of cells generate representations.

When I have collected enough data to answer the important questions I spend quite a bit of time looking at it, thinking about controls, alternative explanations. Occasionally during lunchtime I have interesting and often heated discussions with colleagues on various topics – I like that part of the academic scientific life quite a bit as well.

Why is your work important?

Understanding the brain is one of the most important scientific quests. After all, who we are and the way we think are mostly because of our memories and the interaction of different parts of the brain. I think the hippocampal formation is an especially interesting part of the brain in this respect. We know enough about it to begin to ask really important questions about mechanisms, i.e. how the structure handles all the mathematical operations it performs to form a cognitive representation of space.

Although I’m driven in my day-to-day research by curiosity, I hope that in the longer run our understanding of hippocampal memory mechanisms will provide the basis for attempts to cure diseases such as Alzheimer’s.

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

I am hoping/dreaming that one day I’ll come up with a theory of hippocampal function. Another big goal is to be able to use this knowledge to implant memories in the brain.

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

During my MRes course in Bioimaging science at Imperial College, I went to a general neuroscience lecture where Kit Longden (a post-doc in our lab) was talking about the brain. He said that there are maps of the environment in our brain. I thought that this was the coolest thing I ever heard! So I contacted Prof John O’Keefe at UCL and asked if I could work with him. Luckily he accepted me to do a PhD. It was great to get into grid cell recording at the ground floor at a time when we still know very little about how they function.

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

It is probably the answer you hear the most but I am glad I have an opportunity to spell it out as well: A LOT! I received my Sir Henry Wellcome Fellowship straight after my PhD, which was great since I got the chance to formulate an idea, a project, and work on it with any lab I chose. And I got to work on it in several world-class labs. Wellcome basically told me: we like your project (high risk, high gain!), here are the resources, go and solve the problem.

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

“When are you going to cure Alzheimer’s disease?”

As I said above, I’m primarily a basic researcher interested in blue-sky questions but recently I have taken up the opportunity to get involved in a high-powered consortium effort aimed at understanding and hopefully contribute to a cure for Alzheimer’s disease.

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

“When are you going to cure Alzheimer’s disease?”

Because I cannot answer it! My grandma has Alzheimer’s disease. It is very devastating. I wish we could advance our understanding quicker. Hopefully we will have some success with this new initiative and after some time I will have a new “dread” question.

Tell us something about you that might surprise us…

I have competed in a national Eurovision song contest. We lost, so I decided to pursue science instead.

What keeps you awake at night?

My cat. I usually sleep quite well when I have the chance.

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

‘Do the experiment!’  – John O’Keefe

Meaning: do not be afraid to be wrong both in your assumptions about how things work and sometimes wasting your time on what might at the beginning seem like ‘a very dumb idea’.

The chain reaction question – posed by previous spotlit researcher, Dr Arun Shukla, is this: Do you still work on the bench? If not, how badly do you miss it?

Yes, I am spending quite a bit of time doing experiments or preparing for them. I hope it will never change. I think that’s what being a scientist is largely about (at least if you’re an experimentalist) – making hypotheses and testing them. I think it does not matter how good one is in planning and generating ideas, there are always surprises awaiting you in a lab.

 

Women in Science – Supporting and developing great talent

12 Mar, 2015

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“Be bold”, “be confident” and “be yourself” – just some of the positive advice that came out of the Wellcome Trust’s Women in Science event last week. Co-hosted with Aberdeen Asset Management, the event brought together current and future leaders from science, media, finance and industry to share their experiences, explore existing challenges, and propose novel ideas to improve workplace diversity and retention of talent. Hannah Laurence reports on some of the main themes, messages and initiatives discussed at the event…

At the Wellcome Trust we seek to support our grantholders as best as we can. Results from our career tracker survey have indicated that a lack of mentoring, career support and role models may be factors contributing to the number of women leaving science earlier in their careers than men.

It is widely recognised that women are underrepresented in the top tiers of organisations – not only in scientific research, but across a range of sectors, including the media, finance and the corporate world. As part of our wider aim to attract and retain talented individuals within research, the Women in Science event was designed to bring together professionals, from an array of backgrounds, in surroundings that stimulated open and frank discussions around the topics of diversity, talent management and career progression. As well as listening to experiences from within the research sector, sharing and learning from other areas, such as industry, can contribute towards our wider aim of attracting and retaining talented researchers.

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A “leaky pipe”

The day began with thought-provoking introductory remarks from Governor of the Wellcome Trust, Professor Dame Kay Davies, and Aberdeen Asset Management’s Chief Investment Officer, Anne Richards. They both noted that while career opportunities for women have certainly improved over the years, the pace of change has been slower than anticipated (or hoped for). Stark figures showing the “leaky pipe” of women in science set the scene for subsequent discussions. How do we attract women into STEM careers? – and importantly, what needs to change in order to keep them?

With nods of strong agreement that more needs to be done to even-out the gender balance and increase diversity, it was time to get down to the nitty-gritty, and explore which strategies could actually make a difference. Throughout the event, speakers and audience members tackled tough questions around improving the gender balance (especially in senior roles), and how organisations, institutions and companies can benefit from diversity.

While all of the contributors and participants agreed that the challenges are complex, there was still room for some healthy debate around the way the issues are articulated, and the solutions put forth to help solve them.

Forging paths

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Speakers on the first panel shared their personal tips on confidence building and career progression. Professor Carol Robinson, recommended media training, and also said that assertiveness training can help people be clearer in communication and find their voices. Pfizer’s Dr Ruth McKernan emphasised the need to have the confidence to be yourself at work. She also spoke about the importance of pursuing a career you feel passionate about.

Professor Jane Clarke astutely pointed out “if you have a leaking pipe, you don’t blame the water” – a sentiment echoed later on in the day by Kathryn Koch at Goldman Sachs, who reflected: “we focus a bit too much on ‘fixing’ the women. Stop trying to fix women, and fix management.”

The speakers, despite their varied backgrounds, agreed that being a successful leader is not about changing yourself to match other people’s expectations – nor is it about emulating other successful colleagues. As Baroness Eliza Manningham-Buller, Wellcome Trust Governor (and next Chair otemplate pic2f the Trust), stated: “There is no template”.

The theme of confidence was woven throughout the day, although there was recognition that confidence can only get you so far. In order for bright, talented individuals to succeed, there must be structures and systems in place to ensure that working environments reflect and embrace diversity.

What can funders and shareholders do?

With representatives from the Science Museum Group, Medical Research Council, Wellcome Trust, BBSRC and Aberdeen Asset Management on the panel, the question of what grant-making bodies and shareholders can do to improve the situation was explored.

The panel touched upon recruitment practices and discussed the pros and cons of a range of ideas, including setting quotas; anonymising applications; unconscious bias training for interview panels and linking compensation to diversity matters. They also looked at funding and the issue of retaining talented individuals – regardless of gender. Dr Jim Smith, MRC, talked about the importance of supporting not just women, but families.

The BBSRC’s Jackie Hunter discussed how they are going out to talk to the institutions where there are largest discrepancies in diversity to find out why this is the case. She also reminded us that we should all hold ourselves accountable for our actions when we see behaviour that is not helping diversity.

Professor Dame Kay Davies and the Wellcome Trust’s Ted Smith also touched on the Trust’s flexible support that is available for researchers at all career stages. This includes enhanced maternity and paternity leave provision for researchers, acknowledging the impact of caring responsibilities beyond the period of time formally away from work.

Learning from others

Professor Eleftheria Zeggini from the Wellcome Trust Sanger Institute gave us a whistlestop tour of the “Sex in Science” programme she leads at the Sanger Institute. This initiative is helping to create a more supportive environment for employees and their families, with positive results so far. One of the creative steps they have taken is to create an onsite nursery, which helps to provide extra flexibility for individuals working at the Sanger Institute.

C0111921 'Women in Science' eventThe University of York’s Chemistry department has made great progress since 2004, when they took the step to base their approaches on hard evidence, rather than anecdotes and hearsay. Professor Paul Walton shared his take on the successful initiatives implemented. A key component has been to introduce a policy that allows any researcher to work part-time, with a guarantee that they can return to full-time employment at any point in the future.

Despite initial reservations from the university from a finance perspective, it transpired that instead of increasing costs, it actually saved money in the long term. Both men and women took up the opportunity to be more flexible, with the additional (and unforeseen) effect of helping to de-stigmatise part-time working.

Cultural change cannot happen overnight of course, and Professor Walton explained it has taken the department around ten years to see a discernible and measureable impact. Adding his thoughts on an earlier question about engaging men with the issues, his observation was that when language switched from being focused on women to being about ‘fairness’, men were much more eager to engage with the issues.

Sponsors vs Mentors

“A mentor is someone you can talk to, a sponsor is someone who will talk about you when you’re not in the room” said Kathryn Koch, addressing a question as to the distinction between the terms.

Both roles had been mentioned at various times during discussions, and while there was widespread support for mentors – “a mentor will hold up a mirror to you; it’s tough love but invaluable” said Dr Gill Samuels – the notion of sponsors split the room.

Professor Jane Clarke was adamant that sponsors – people who help to promote you to others – are akin to “the old boys’ network”, which should be broken down rather than encouraged. Others disagreed; taking the view that assigning sponsors in leadership or decision-making roles to individuals earlier on in their careers could be an effective tool for promoting diversity.

Embracing diversity

aone 5We heard the case for having wide diversity in the workplace throughout the day and there is no doubt that those in the room understood the importance and benefits of it. Despite this we also heard that many organisations may still struggle with how to push the topic up the agenda and make changes in sensible and practical ways.

Speakers from both industry and the financial sector set out the clear business case for a diverse workforce, with creativity, innovation and competitive advantages all being noted. Focussing on the business need for diversity has helped them to introduce initiatives to attract and retain talented people.

Diversity within the workplace has many benefits to the overall success of organisations. As Professor Dame Anne Johnson and others pointed out, diversity is not solely a matter of gender- we can all benefit from a mix of ideas, approaches, and experience.

At the end of an energising day, the message was clear – everyone needs to be involved and accountable for what we, and our organisations, can change in order to help talented individuals achieve their full potential – and judging by the atmosphere at the event, there is no shortage of ideas or enthusiasm to make changes for the better.

You can find out more about the way that the Wellcome Trust supports flexible research careers and read about our Career Re-entry Fellowships. If you’d like to see what advice attendees of the Women in Science event offered others in the field, take a look at our blog post celebrating International Women’s Day 2015.

Let’s talk about sex (education): The changing terrain of sex and relationships education

10 Mar, 2015

Let's talk about sex education

Despite a trend towards increased openness to a diversity of lifestyles, sex education remains a topic that attracts diverse, and often polarised, opinions on how when and where young people should be taught about sex. Wellcome Trust Governor Professor Dame Anne Johnson, a sexual health and infectious disease researcher, and Dr Clare Tanton, an epidemiologist at University College London, discuss the latest research findings on how young people learn about sex and how this is associated with their sexual behaviour…

How we best deliver sex education to young people – and what we teach them – often provokes fierce debate amongst health and education specialists, politicians, parents, and community leaders. But we hear much less of the voices of young people. What are their views, needs and reflections?

This week we published new findings from the British National Surveys of Sexual Attitudes and Lifestyles (Natsal), in which we asked a random sample of almost 4000 young people aged 16 to 24 to look back on their experience of sex education and to report in self-administered interviews how they learned about sex, and what they thought about that.

The Natsal surveys are among the largest and most scientific studies of sexual behaviour in the world and are a collaboration between UCL, the London School of Hygiene and Tropical Medicine and NatCen Social Research. The current survey (Natsal-3, carried out 2010-2012) is the third in a series conducted approximately every 10 years, and was funded by the Medical Research Council and the Wellcome Trust, with additional funding from the Economic and Social Research Council and the Department of Health.

AS0000153FC07 Primary school, children in sex education classFor both men and women, school is now the most commonly reported main source of information about sexual matters, increasing from 28% in 1990 to 40% in 2010. School is generally replacing less reliable sources too: fewer men now say friends were their main source and fewer women report their first sexual partner as their main source. In addition, those who reported school as their main source of information had their first experience of sexual intercourse later than those who reported a different main source of information, and generally had fewer poor sexual health outcomes later in life. So the increasing prominence of school is encouraging as it has the potential to reduce inequalities in access to reliable information.

Parents featured much less frequently than school as a source of information, particularly for men, and were the main source for only 7% of men and 14% of women. But around half of young people still reported that they got most of their information from a less ‘authoritative’ source like friends, their first sexual partner, media sources or pornography. And, less positively, most young people still told us that they felt they ought to have known more when they first felt ready for sexual experience.

The things they most commonly wanted to know more about (sexual feelings, emotions and relationships, STIs and contraception) indicate a gap between their needs and what is actually covered by current requirements for sex and relationships education (SRE).

The terrain that young people have to navigate has changed considerably over the past 20 years. With increased availability of the internet comes access to a wealth of high-quality information, but also access to a lot of less-reliable information and sexually explicit content. This is an area where even the most technologically savvy parents would lag behind their children.

The current government guidance on SRE dates from 2000, so cannot encompass these more recent societal changes, and therefore potentially leaves young people unprepared. A broader framing of sex education is required to cover not just the biology of sex, but also healthy relationships, sexual consent, exploitation and abuse, the impact of pornography, and gender issues.

A recent Education Select Committee inquiry into personal, social, health and economic education (PHSE) and SRE recognised the importance of both in equipping young people with the broader education and skills they need, recommending that both become statutory at school.

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The report also stresses the importance of schools and parents working together and our findings echo this – young people want their information needs to be met by school and parents. It was striking that far more men wanted information from their fathers than received it. We know that there is little in the way of formal help for parents to support them in talking to their children about sex and many may find this a difficult subject to broach.

What we heard from young people’s responses to Natsal was also reflected in the Wellcome Trust Sounds of Sexology project, which was linked to Wellcome Collection’s exhibition, The Institute of Sexology. This innovative project saw groups of young people from around the country, collaborating with researchers and songwriters to compose music and lyrics drawing on their own experiences and inspired by sex research.

We had a wonderful night out at the Roundhouse with an incredible array of talented performers moving us to tears of joy and sadness with songs that ranged through themes of sexuality, sexual violence and a history of sexology. In that context, the anthem ‘Hail Marie’ took on a new meaning, celebrating the life of Marie Stopes the early 20th Century pioneer of contraception to whom all women owe a debt of gratitude for access to safe contraception today.

The Wellcome Trust has long been a pioneer funder in this field, supporting both the first and third Natsal surveys. It continues to fund innovative projects, including the current national Sexology Season, which features a series of events in Manchester, Brighton and Glasgow, as well as in London at The Institute of Sexology.

Alongside the Natsal evidence, we hope these types of projects contribute to debate and policy discussions, which will ultimately improve the sexual health and wellbeing of young people in the future.

You can access the full research findings in BMJ Open and the main Natsal findings from 2013 are explored in this playful infographic, Sex by Numbers (a book of the same name is due to be published in April). The Institute of Sexology runs at Wellcome Collection until September 2015, with learning resources available for helping young people toward greater engagement with the content of the exhibition.

Image credits: Let’s talk about sex is a derivative of Profusion of nectar – by  Max Westby on Flickr – CC-BY-NC- SA, by Kate Arkless Gray/Wellcome Trust – CC-BY-NC-SA;  Primary sex education – by Anthea Sieveking , Wellcome Images, Teenage sex education – by Anne-Katrin Purkiss, Wellcome Images.

 

Wellcome Trust Research Round-Up: 09/03/2015

9 Mar, 2015

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

New therapy developed to treat lung cancer

B0006911 Lung cancer cellScientists have developed a new technique that uses gene therapy and stem cell therapy in combination to treat lung cancer. Researchers led by Professor Sam Janes, a Wellcome Trust Senior Research Fellow at UCL/UCLH, will carry out the first UK clinical trial in NHS patients later this year.

The treatment uses stem cells as a delivery vehicle for an anti-cancer gene. This gene induces a self-destruct pathway in cancer, but not healthy cells. Being encased within a cell protects the genetic material from being degraded by the body so that when it reaches the tumour it is able to trigger a process that kills the cancer cells.

A key advantage of the treatment is that the cells do not need to be from a close relative or tissue match. This is because they have relatively few proteins on the surface and do not induce an immune response in the recipient.

Early tests of the experimental treatment on mice have shown it can reduce and in some cases clear tumours. The team will now test the treatment in human volunteers, firstly to check that the treatment is safe, and then in 56 lung cancer patients to see how effective the therapy is compared with standard care.

Principle Investigator Sam Janes, Professor of Respiratory Medicine at UCL and Consultant in Respiratory Medicine at UCLH, said: “Lung cancer is very difficult to treat because the vast majority of patients are not diagnosed until the cancer has spread to other parts of the body. We aim to improve prospects for lung cancer by using a highly targeted therapy using stem cells. Once there, they switch on a ‘kill’ pathway in the cancer cells, leaving healthy surrounding cells untouched.

He added: “If clinical trials are successful, our treatment could be transformative for the treatment of lung cancer, and possibly other types of tumour in future.”

Millions of Asian men living today descended from 11 powerful leaders

Genghis KhanGeneticists from the University of Leicester have discovered that millions of modern Asian men are descended from 11 powerful dynastic leaders – including Mongolian warlord Genghis Khan – who lived up to 4,000 years ago.

The study, which is funded by the Wellcome Trust and published in the journal European Journal of Human Genetics, examined the male-specific Y chromosome, which is passed from father to son, in more than 5,000 Asian men belonging to 127 populations.

Most Y-chromosome types are very rare, but the team discovered 11 types that were relatively common across the sample and studied their distributions and histories.

The project’s leader, Prof Mark Jobling from the University of Leicester’s Department of Genetics, explained further: “The youngest lineages, originating in the last 1700 years… were highly mobile horse-riders and could spread their Y chromosomes far and wide. For these lineages to become so common, their powerful founders needed to have many sons by many women, and to pass their status – as well as their Y chromosomes – on to them. The sons, in turn, could then have many sons, too.”

How young men and women learn about sex and relationships

L0029516 CMAC, What Parents should tell their childreMore young people than ever are getting most of their information about sex from school, but most feel they are not getting all the information they need, according to new research published in BMJ Open.

The findings come from the third Wellcome Trust and MRC-funded National Survey of Sexual Attitudes and Lifestyles, the largest scientific study of sexual health and lifestyles in Britain. Researchers compared data from nearly 4,000 men and women aged between 16 and 24 collected between 2010 and 2012 with that from previous surveys in 1990-91 and 1999-2001.

They found that for both men and women, school is increasingly reported as a main source of information about sexual matters, having risen from 28% in 1990 to 40% in 2012. However, around half of people reported getting most of their information from less authoritative ‘other’ sources such as their first sexual partner, friends, siblings, media sources, and pornography.

Most people in the study (70%) said they felt they ‘ought to have known more’ when they first felt ready for some sexual experience. They specifically said they wanted more information about ‘sexual feelings, emotions and relationships’, as well as STIs, and for women, contraception.

Study author, Wendy Macdowall, Lecturer at the London School of Hygiene and Tropical Medicine, said: “Our results suggest we need a broader framing of sex education in schools that addresses the needs of both young men and women, with a move away from the traditional female-focused ‘periods, pills and pregnancy’ approach….but it’s also important to remember that introducing statutory SRE [Sex and Relationship Education] in schools won’t solve everything. The factors influencing poor sexual health are multiple and complex and so too must be the solutions to them.”

In other news

The Newton Fund is a new initiative intended to strengthen research and innovation partnerships between the UK and emerging knowledge economies. The Wellcome Trust, in collaboration with the MRC, is now accepting applications for Newton Fund research activities that fall in our funding remit in South-east Asia.

aone 10The Wellcome Trust hosted a Women in Science event on Thursday 5th March. We asked attendees to share their thoughts and advice on encouraging women in the field, which are collected here. Look out for a further post summarising the event later this week.

Mosaic, the digital publication from the Wellcome Trust, is celebrating a year of exploring the science of life with long-form science journalism. To coincide with this anniversary they are launching a series of podcasts from the past year’s articles, beginning with three of the most popular stories so far. Further podcasts will then be released weekly, and can be accessed via iTunes and RSS feeds.

Image credits: Lung cancer cell – Anne Weston, LRI, CRUK, Wellcome Images; Genghis Khan by Anonymous court painter – from WikiMedia Commons; What Father’s Should Tell their sons – Wellcome Library, London; Women in Science – Kate Arkless Gray/Wellcome Trust – CC-BY

 

Celebrating International Women’s Day

8 Mar, 2015

The theme of International Women’s Day 2015 is “Make it Happen”, so we asked attendees of the Wellcome Trust’s Women in Science event to share their thoughts and advice on encouraging women in the field. Here is a selection of their responses – what would you add? Share your suggestions in the comments section, or add them on Twitter using the #WomenInScience hashtag.

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Working in conjunction with Aberdeen Asset Management, the Wellcome Trust’s Women in Science event brought leaders from science, academia and business together to share their thoughts on how to reduce gender disparities in science. Look out for our post about the event next week – and check out some of the tweets from the event here.

Image of the Week: In the flesh

6 Mar, 2015
In the Flesh - Courtesy of Gemma Tickle/Mosaic

In the flesh – Courtesy of Gemma Tickle/Mosaic

This week we’re celebrating the 1st birthday of our long-form science journalism publication Mosaic. We’ve had a spectacularly successful 12 months, with over 50 stories published that have reached in excess of eight million readers – on our site, and via other outlets who have taken advantage of our Creative Commons licensing to share stories with their audiences. Peta Bell is the Art Director for Mosaic and we asked her to select a favourite image from the past 12 months and tell us how she goes about illustrating the varied (and often complex) stories that Mosaic publishes…

Coming up with images for Mosaic really is a collaborative process.

The subject matter is always well researched from the writers’ end, so I find the most efficient way to produce imagery is to wait to read the copy before finding the right image-maker and commissioning images.

Images need to cover not only the essence of the piece, but also need to be factual correct and relatable – even if the end result is quite conceptual, like the image above.

This particular piece by Gemma Tickle was commissioned for a story on circumcision and what Gemma pulled out of the text was how clinical the procedure was. She was interested in the idea of infection, disease and cleanliness when it came to circumcision, and whether it was done for a religious or an economic reason.

Gemma decided she wanted to make phallic forms using plasticine, plastic and wood, and play around with reflections to bring the piece together. The image above shows a phallic object made from wood, which not only plays the physical form of a penis, but also the slang for penis. It’s simultaneously silly and clever – and a fun fact about it is that it was made by a man with the surname “Wood”.

The series of images in the article was also produced, made and photographed by women (photographed by the wonderful Kate Jackling), which made for a few awkward conversations on set but I genuinely feel worked out to be the most objective and creative way of dealing with the subject matter.

You can see the full set of images that this image is part of and read the full story “The troubled history of the foreskin” on the Mosaic website. Mosaic publishes a new piece each week on a Tuesday, and you can keep up to date with them on Twitter, Facebook, and Instagram.

Image credit: Gemma Tickle for Mosaic Science

The Reckoning: An Analysis of Wellcome Trust Open Access Spend 2013-14

3 Mar, 2015

Cost of Open Access

To help make the costs around open access more transparent, the Wellcome Trust has published details on how much it spent on article processing charges in the year 2013-14. The data also shows to what extent the services the Trust has paid for – i.e. that the final, publisher-formatted versions of articles are freely available in Europe PubMed Central with a CC-BY licence – have been delivered. Robert Kiley, Head of Digital Services at the Wellcome Library, provides an analysis of what the latest data reveals...

Once a year we ask all those institutions in receipt of an open access (OA) grant from the Trust to provide details on how the grant has been spent. In addition to simply calculating the total spend, and the average article processing charge (APC), we have, for the first time, done an analysis of the licence types that have been applied to these articles. The licence analysis was undertaken to determine to what extent articles had been published under the Creative Commons Attribution licence (CC-BY), in line with our OA policy.

Cost data

In headline terms, some 2556 articles were published under an APC model, and the total spend for the year 2013-14 was just under £4.7 million. The average APC was around £1837, whilst the median cost was £1800. Table one, shows how these figures compare with the previous year (2012-13).
Open access spend Wellcome Trust

The takeaway form this is that more Trust-funded articles are being published via the OA APC route – an increase of 20% – whilst APC fees are relatively static (an increase in the average APC of just 0.8%).

Focusing just on 2013-14 data, Table two provides a breakdown of the type of journal where the articles were published, and the average APC for each type. A fully OA journal is one in which every article is made OA (e.g. PLOS One, Cell Reports etc.), whereas a hybrid journal is one which is still published under a subscription model, but where individual articles can be made OA. The “unknowns” in table two are those that we were unable (programmatically) to determine if the article was published in a fully OA or a hybrid journal.

Open access spend Wellcome Trust

Although Wellcome Trust authors are publishing large numbers of papers in fully OA journals (around 24% of all papers in this cohort), there is still a very strong desire to publish in traditional, subscription-based journals, albeit via the OA, hybrid route (in line with the Wellcome Trust policy).

The second key finding is that the average APC levied by hybrid journals is 64% higher than the average APC charged by a fully OA title. This higher average fee is despite the fact that hybrid journals also enjoy a revenue stream from subscriptions.

Faced with similar data showing the high price of APCs charged by hybrid journals, a number of organisations – including the German Research Foundation, DFG, and the Norwegian Research Council – do not allow OA grants to be used to fund APCs in hybrid journals.

Given the scale of hybrid OA publishing amongst Trust-funded researchers, such an approach would seriously limit the ability of many of our researchers to publish in their journal of choice, and therefore we have (to date) decided not to go down this path.

However, we do feel that the hybrid APC market is not working effectively and we are actively exploring other ways to tackle this marketplace’s current dysfunctions. By way of example, the FWF (Austrian Science Fund) have recently imposed a cap of €1500 for hybrid articles. We will watch with interest whether this cap leads to any change in author behaviour (i.e. authors start to consider price when they are submitting an article for publication), or changes to publishers’ APCs.

Our final table on costs provides an analysis of the top five publishers (by volume of Trust-attributed articles published).

Open access spend Wellcome Trust

What is significant here is the degree to which the two traditional, subscription-based publishers (Elsevier and Wiley) still dominate the field where Trust authors seek to publish. Together, these two publishers represent some 40% of our total APC spend, and are responsible for 35% of all Trust-funded papers published under the APC model.

It is also interesting to note that the average APCs for the fully OA journals published by Elsevier and Wiley are significantly higher than those charged by competitors at PLOS, BMC and OUP.

Compliance data

The other reason for collecting this data is to check whether the publisher has provided the service we demand in return for paying an APC.

When Trust funding is used to cover an APC, the publisher has to provide a number of specific services. These include depositing the final version of the article in PubMed Central (PMC) at the time of publication (this content is then mirrored to Europe PMC) and attaching a CC-BY licence to the article, thus making is clear that anyone can re-use that work for any purpose, subject to the norm of attribution.

To help us check compliance in a more automated way, we commissioned Cottage Labs to develop a “compliance monitoring” tool to programmatically determine whether the paper is in the Europe PMC repository and what licence (if any) is attached.

A summary of the key compliance findings is presented in table four:
Open access spend Wellcome Trust

The headline data is disappointing – particularly in terms of the relatively high numbers of papers which are not in the Europe PMC repository.

To investigate this further, we undertook a manual exercise to determine if these articles were freely available on the publisher site and/or were published “ahead of print”. The latter distinction is important as the PMC repository only accepts the final version of the article, and thus it not possible for a publisher to deposit a paper that is released online “ahead of print”.

The results of this exercise are shown in table five:

Open access spend Wellcome Trust

Table five shows that typically publishers are making APC-funded papers OA on their sites. This suggests therefore that, for some publishers the problem is confined to being able to consistently deposit papers at PMC. By way of example, of the 325 papers that were not in Europe PMC, 110 of these (34%) were published by Wiley.

It is also interesting to note that 23% of the papers are classified as “early view” papers, and that in the fullness of time we can expect most (all) of these papers will be deposited in PMC (and mirrored to Europe PMC). Looking across this cohort of papers we can see a wide range of early view publication dates, with the oldest article (not yet formally published) originally published online in October 2013.

However, even if we assume that all the early view papers will be deposited, this still means that 237 papers, available in final published form, for which APCs totalling over £480,000 have been paid, are not available in Europe PMC.

This is unacceptable.

Licence compliance was always going to be more problematic – authors do not always fully understand the Trust’s requirements, a situation compounded by some publishers who persist in offering a choice of licences to Trust funded authors – but we do now have a baseline compliance rate (61%) to build on.

Action Areas

As a matter of urgency the Wellcome Trust has started to follow up with all the publishers concerned, to better understand the problems they are experiencing, and how they plan to rectify them. It is encouraging how responsive publishers have been so far.

Their responses have also highlighted the number and variety of obstacles facing articles destined for open access; obstacles which publishers, funders and institutions must identify and navigate when tracking compliance. Problems identified include:

  • Content not available in PMC, even though the publisher believes they have successfully deposited it;
  • Institutions reporting an APC payment – but publisher has no record of that article ever being flagged as an OA paper (and no invoice was ever raised);
  • Articles submitted for publication before the CC-BY requirement was introduced (1st April 2013);
  • Ambiguous (or no) licence information in the article;
  • Contradictory licence information (the human readable text says one licence, the licence encoded in the XML cites a different one);
  • Author has selected an alternative to the CC-BY licence (either erroneously, or otherwise), presumably unaware of the sanctions the Trust has defined for non-compliance).

Pinning down which of the above issues relates to which specific articles is a moving target, but the numbers involved indicate clear trends and challenges.

It is clear that early view articles pose another challenge; it is only possible to identify whether the article is early view manually, and if it is, the months which elapse before its final publication (and deposit in PMC/Europe PMC) are still troubling. The Trust is discussing this issue with staff at PMC to see if a policy change can be made, such that publishers can (for papers funded by named funders) deposit an early view paper and follow-up with the final, published version, in due course.

We will also be following up with institutions with regards to our CC-BY requirement and we will make it clear that, going forward, any APC costs associated with papers that are not licenced CC-BY cannot be met from Trust funds.

We will also be ensuring publishers are aware of their obligations to ensure papers associated with our funding are deposited and licensed in line with our requirements where an APC is being charged. We will also make clear our expectation that the licences are encoded in a consistent, machine-readable way.

Moving forward, in cases where particular journals or publishers consistently fail to deliver the services that have been paid for, we will declare them to be non-compliant with our OA policy, and alert researchers and institutions to this, including through the Sherpa FACT service. More generally, we will encourage all researchers and institutions to actively consider whether the APC they are being charged by a particular journal is justified in light of the quality of service they receive.

Conclusion

Last year, when we released our first set of APC data, I published a blog post that concluded by saying that we expect every publisher who levies on open access fee to provide a first class service to our researchers and their institutions.

One year on, there are still significant problems – especially in terms of depositing content in PMC and licensing this in accordance with our requirements – and the first class service called for still seems to be some way off. These problems are particularly prevalent amongst publishers offering a hybrid OA option, which, as discussed above, is also the more expensive way to comply with our OA policy.

The Trust remains committed to its OA policy, but ultimately if we are to be successful and get to the point where all Trust funded research is OA, then the friction in the system – which is all too evident in this analysis – has to be resolved.

You can read the Wellcome Trust’s OA policy on our website and if you’re interested in exploring our 2013-14 APC data set you can find it on Figshare. The underlying code for the Cottage Lab compliance tool we used has been This piece of software has been made available on github under an Apache open source licence, to enable others to take this code and adapt it to suit their specific needs.

Image Credit: Kate Arkless Gray/Wellcome Trust – CC-BY

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