Features

A hydrogel material promises better treatment for cleft palates - a birth defect that affects 1 in 700 babies in the UK.

As today's Daily Mail reports the breakthrough comes from work by researchers at Oxford University, the John Radcliffe Hospital, and the Georgia Institute of Technology using STFC's ISIS neutron source.

The team, including Jinhyun Hannah Lee and Zamri Radzi from Oxford University's Department of Materials, used ISIS to look at the hydrogel polymer's molecular structure in order to see how the material might be used as part of a simplified surgical treatment.

The treatment involves inserting an anisotropic hydrogel material - similar to that used in contact lenses - under the mucosa of the roof of the mouth.

Once inserted, the hydrogel gradually expands as fluid is absorbed, encouraging skin growth over and around the plate. After sufficient skin has been generated to repair the palatal cleft, the plate is removed and the cleft is repaired using this additional tissue.

The success of the preliminary results of self-inflating anisotropic hydrogel tissue expanders means clinical trials are expected to take place early in 2011.

The study is the first to be carried out using the Offspec instrument at the recently opened second target station at ISIS.

Offspec is the world’s most advanced neutron instrument for studying new surface structures and can be used for a number of applications including biological membranes and patterned materials for data storage media.

Read more about the research in this ISIS release

Oxford University's technology transfer company Oxford University Innovation is looking for commercial partners to help develop the technology, for more details, contact Renate Krelle: [email protected]

The reddest part of Jupiter’s Great Red Spot corresponds to a warm core within this otherwise cold storm system.

The discovery comes from new thermal images taken by ground-based telescopes that have enabled scientists to make the first detailed interior weather map of the Solar System’s biggest storm.

The international team, including scientists from Oxford University and NASA JPL, used thermal images from the Very Large Telescope (Chile), Gemini Observatory telescope (Chile) and Japan’s Subaru telescope (Hawaii). They report their findings in the journal Icarus.

‘This is the first time we can say that there’s an intimate link between environmental conditions - temperature, winds, pressure and composition - and the actual colour of the Great Red Spot,’ lead author Leigh Fletcher, from Oxford University’s Department of Physics, told me.

‘Although we can speculate, we still don’t know for sure which chemicals or processes are causing that deep red colour, but we do know now that it is related to changes in the environmental conditions right in the heart of the storm.’

As well as this warm ‘heart’ the images show dark lanes at the edge of the storm where gases are descending into the deeper regions of the planet.

One of the most intriguing findings is that the most intense orange-red central part of the spot is about 3 to 4 Kelvin warmer than the environment around it.

Leigh explains that while this temperature differential might not seem like a lot it is enough to allow the storm circulation, usually counter-clockwise, to shift to a weak clockwise circulation in the very middle of the storm. Not only that, but on other parts of Jupiter the temperature change is enough to alter wind velocities and affect cloud patterns in the belts and zones.

‘This is our first detailed look inside the biggest storm of the solar system,’ said Glenn Orton, a senior research scientist at NASA’s Jet Propulsion Laboratory, one of the authors. ‘We once thought the Great Red Spot was a plain old oval without much structure, but these new results show that it is, in fact, extremely complicated.’

Unlocking the secrets of Jupiter’s giant storm systems will be one of the targets for infrared spacecraft observations from future missions including NASA’s Juno and the NASA/ESA Europa-Jupiter System Mission concept.

Dr Leigh Fletcher is based at Oxford University’s Department of Physics

In the 1970s Oxford University engineer John O’Connor with surgeon John Goodfellow invented the Oxford Knee.

This prosthetic device, which has gone through many incarnations since, is an alternative to complete knee replacement, helping patients recover mobility faster after the operation and giving them an implant that, in over 90 per cent of cases, lasts for over 20 years.

It’s a great example of where an engineering idea results in a successful new medical technology but for every success story are other ideas that aren’t as commercially viable or don’t address a real clinical need.

So how can we ensure that tomorrow’s young engineers invent new technologies that will transform patients’ lives?

Ideas into products
Part of the answer could be found in the new Centre for Doctoral Training [CDT] in Healthcare Innovation which is officially launched today at Oxford University’s Institute of Biomedical Engineering [IBME].

It’s one of 44 new CDTs supported by the Engineering and Physical Sciences Research Council [EPSRC] as a focal point for PhD training in the UK - Oxford now has four such centres.

‘Biomedical engineering is an applied subject that aims to have clinical impact,’ Alison Noble Director of the CDT, tells me, ‘so it’s important to understand  that not all good research ideas make good products, and that listening to customer needs, in our case clinicians, can suggest the best research questions to work on that lead to useful solutions – and profits.’

The new centre aims to equip a new generation of postgraduate researchers not just with traditional academic biomedical engineering skills, but with an appreciation of the clinical environment in which new inventions have to succeed, and the routes to commercialising a new product or service.

So what’s different about training at the CDT?

‘The traditional doctoral training route focuses on research training in one sub-discipline of biomedical engineering. This is an excellent route for students who know exactly which research area they want to work in, but the onus is on the student to fill in their gaps of knowledge and build up an interdisciplinary skills base,’ Alison tells me.

‘By contrast the CDT programme provides a solid grounding of advanced biomedical engineering research skills and an introduction to healthcare technology commercialisation and clinical translation up-front in the first year.’

Understanding these issues from the very start of their doctoral training, before they specialise, is, she believes, very important so that this understanding can inform the development of each student’s research.

As part of the 4 Year DPhil programme at the CDT students cover three key themes; Information Driven Healthcare, Modelling for Personalised Healthcare and Cancer Therapeutics and Delivery.

Software to cancer therapy
Each theme is an area already being investigated at the IBME, so in information-driven healthcare, for instance, Oxford researchers are currently looking how to use intelligent signal processing methods to automate the monitoring of signals from devices in the ITU, and developing software-based clinical decision-support systems for monitoring breast cancer treatment.

Whilst in cancer therapeutics and delivery on-going research includes work on molecular imaging, development of ultrasound-based methods for detecting early response to cancer therapy, monitoring of high-intensity focused ultrasound, and new drug delivery technologies.

But the programme is about more than academic research:

‘We want students to consider careers in industry as well as academia and we offer various activities over the 4-year programme: business and entrepreneurship modules, seminar series, events, and placements or PhDs involving industry partners,’ Alison explains. ‘These aim to expose students to the breadth of the healthcare industry and associated businesses to enable them to make an informed decision about their future careers.’

The goal is for the CDT to form the focal point for postgraduate training at the IBME over the next 8 years, with an estimated 75-100 students passing through the programme, providing an invaluable alternative to traditional doctoral training.

Alison tells me: ‘we want to make the CDT a flagship postgraduate programme in the UK and internationally, and judging by the quality of overseas applications we are receiving, it has strong global appeal. We already have one university-funded overseas scholarship and are looking to raise funds for more.’

‘Our aim is, whether they work in industry or academia, for our graduates to go on to become global leaders in their field.’

Professor Alison Noble is Director of the new CDT and is based at the IBME, part of Oxford's Department of Engineering Science.

Bad news from Kenya: severe flooding has destroyed a major elephant research facility which is home to Oxford University scientists.

Fortunately no one has been reported hurt, but the unexpected flooding of the Ewaso Ng’iro River has completely destroyed the Save the Elephants [STE] research facility and Elephant Watch Safari Camp located in Samburu National Reserve, Kenya.

Vital research data and equipment has been lost and people have had to be evacuated.

Lucy King, an Oxford University DPhil student who works at the facility and has done recent research on beehive fences and elephants and bees, reported that at 5am yesterday 'a wall of water akin to a Tsunami' decimated first the Safari Camp and then, two hours later, the Save the Elephants research facility.

Researchers and staff managed to drive to safety within seconds of the flood waters surging through the facility.

Lucy told me yesterday: 'We are all devastated to have lost our research camp that had only just been renovated. Our staff are still stuck there and sifting through the mud trying to salvage what they can, more rain is coming tonight, it's a real catastrophe.'

Key research data, computers, equipment, kitchen facilities and food, lodging and personal effects have been washed away.

The immediate relief process has already begun, with blankets and water flown in by STE founder Iain Douglas-Hamilton, as well as the assistance of the British Army, which is attempting to airlift people to safety and bring additional supplies.

Although it is too early to assess the cost of the damage Lucy, who is Operations Manager at the facility, says it will cost hundreds of thousands of dollars to rebuild.

Read updates and find out how you can help at the STE website.

Lucy King is a DPhil student at Oxford University's Department of Zoology.

As 2010 is the 10th anniversary of the Human Genome Project [HPG] we'll be running a series of articles to celebrate. In this post we look back at how far genome research has come in the last decade...

‘It’s hard to think back and remember how we worked then. We were scrabbling around in the dark,’ says Professor Mark McCarthy of the Oxford Centre for Diabetes, Endocrinology and Metabolism [OCDEM], recalling how research on the genetic causes of disease had to be carried out before the human genome was sequenced.

The first draft sequence of the human genome was announced at the White House 10 years ago this June by Bill Clinton, with the promise that it would lead to new ways to prevent, diagnose and treat disease.

Mark McCarthy, who is also at the Wellcome Trust Centre for Human Genetics [WTCHG], is the ideal person to explain what has happened since researchers got their hands on the DNA code and where we are now, 10 years on. Mark’s research aims to identify genes involved in diabetes and obesity, and he has been a leader in international collaborations to use the latest genotyping technology to advance our knowledge in this area.

Genetics of diabetes & obesity
One in ten people either has diabetes now or will get it in future, making it a global health challenge now and in the coming decades.

‘Not everyone exposed to our increasingly sedentary lifestyles becomes overweight,’ says Mark, ‘meaning obesity is the result of a combination of nature and nurture, the effects of genes and the environment.'

‘In diabetes we’ve found just short of 40 genes associated with an increased risk of the condition. For obesity, the number’s similar.’

He adds: ‘For diabetes, some of these genes are involved in cell cycle regulation and so may help in maintaining the cells in the pancreas that produce insulin. Perhaps some people are blessed with more or better islet cells in the pancreas.'

‘The evidence from the genes identified for obesity supports the involvement of the part of the brain involved with appetite and the feeling of satiety. It seems that subtle effects in the neural circuitry in the brain that controls what and how much we eat are involved here.’

For Mark, the importance of the human genome is clear: ‘We can trace all this progress back to the sequencing of the human genome. It was an overwhelmingly positive step which has stood the test of time.'

‘Genetics is one of the tools we can use to unlock the mysteries of disease. By identifying the bits of biological machinery involved, we can then use this to treat disease.’

Sequencing the genome
Before the Human Genome Project, researchers wanting to identify genes involved in disease processes would have to rely on laborious or haphazard techniques – ones that didn’t reveal much detail or ones that gave no sense of the bigger picture.

Researchers might select one or two candidates genes that, at best guess, might be involved in disease (‘many were looked at, many turned out not to be involved,’ says Mark). Or scientists could look at broad genetic markers and see how often they occurred in families – perhaps they were linked or often inherited alongside causative genes for disease.

The human genome gave scientists the data they needed to systematically search for, identify, and determine the roles of crucial genes.

‘The first human genome was a hugely influential and transformative step. It gave us a systematic way of looking at genes and heralded an era when genetics became 'big science' like astronomy and physics,’ says Mark.

Once that first human genome had been sequenced, an obvious next step was to understand the genetic origin of variation between people – to find the 1 per cent of the genome that differed between people and where it was located. This could now be attempted in a comprehensive, systematic way across the 3 billion letters in the human DNA code.

Two international collaborative efforts involving many hundreds of scientists, the SNP Consortium and the International HapMap Project, mapped the locations of common single-letter changes in the DNA code of different people.

With that powerful knowledge in hand, it became possible to see if any of these differences in individual genetic makeup could explain people’s predisposition to common diseases like cancer, heart disease and diabetes.

‘These individual differences were the logical place to start looking for differences in people’s DNA that can lead to disease,’ Mark explains.

‘Three things came together at the same time, creating a 'perfect storm',’ he says. ‘The HapMap project told us where common variation was; improvements in the accuracy and cost of genotyping technology meant we could look at hundreds of thousands of locations on the genome; and there was the realisation that a few hundred samples were not enough. We needed larger-scale studies of thousands of people, or to combine multiple studies to give us reliable results.’

Scanning for genes and disease
The result was a new industry of big, international studies that scanned the whole genome of thousands of people using the latest technology. The studies checked the large number of sites where individual differences were now known to occur, to see whether common genetic variations could be associated with a particular disease or condition. And this huge effort has been very successful.

‘Close to 1000 sites of genetic variation have now been associated with common diseases, such as diabetes, heart disease and cancer,’ Mark says. ‘That is way more than we might have expected and it has given us insights into many diseases.'

'At the same time, the results have also been surprising in that the variants we’ve identified don’t explain more than a minority of the genetic basis for disease, and it has proved harder than we imagined to translate the results of these studies rapidly into new biological insights.’

The fact that, after all these studies, most of the genetic basis for common diseases still remains unknown has led to the concept of ‘missing heritability’. For example, despite almost 40 genes having been connected to diabetes and another 40 to obesity, in both cases the identified gene regions account for only around 10 per cent of the known risk that is inherited of developing these conditions.

‘There has been a lot of discussion about the 'missing heritability', comparing it to dark matter in physics – something that we know must be there but haven’t discovered yet,’ says Mark. ‘There are many possibilities for what makes up that missing heritability.’

The most likely, he says, is that less common or rare variants in the DNA code – which would not arise often enough to be picked up in genome-wide screens – have big impacts. Although rare, some of these variants would be connected with a much greater increased risk of disease over those found so far, and help to account for that missing heritability. And the search is now on.

New technology, new studies
Advances in sequencing technology mean it now should be easier to look for these rare sites and test them systematically for association with common diseases - cancer, heart disease, or even schizophrenia, for example.

Rather than scan the genome as before, checking individual locations (albeit many thousands of them), the aim is now to sequence all of the DNA for thousands of people - with and without disease - and find genetic differences linked with various conditions.

The 1000 Genomes Project is already sequencing the genomes of different people to provide a more complete understanding of sequence variation between individuals than we have had so far. It’s sequenced around 300 people so far. But as the technology improves almost month by month, even larger projects become possible.

‘It took 10 years, $3 billion and many scientists around the world to sequence the first human genome,’ Mark explains. ‘Huge technological changes in the capacity to generate data means a handful of people can now generate a genome in a week for maybe $30-40,000. But these figures are almost out of date as soon as you write them down.'

‘New studies that compare whole genome sequences should be able to pick up common and rare variants in a way that has not been possible to date. There is optimism that this will nail the missing heritability. The first efforts to do this on a large scale are now beginning or being planned.’

Mark McCarthy is part of a new transatlantic consortium of researchers that is setting out to sequence the whole genomes of 3000 people: 1500 with diabetes and 1500 without.’

‘This will be a large effort. 3000 people is ten times the size of any dataset currently available,’ he says. ‘We calculate that the project will allow us to detect variants that are present in 1 in 100 people that are associated with diabetes.'

‘Previously, we’ve done very well at detecting variants present at a level of 1 in 10 people, but there will be many more variants present at lower frequencies that that.’ How soon this new knowledge will translate into new genetics-based medicines?'

‘That’s the big open-ended question. It is very easy to talk about possibilities for new treatments and underestimate the time it takes. But we can take hope where rare mutations causing diabetes have been identified – mutations that may be responsible for perhaps 2 per cent of diabetes cases. It has been possible to use that information to come up with new approaches for diagnosis and treatment for these rare types of diabetes.’

‘It is not out of bounds that we could do something similar with the information we obtain in these new sequencing studies,’ says Mark.