Oxford Science Blog

Global efforts to try and treat and eradicate malaria are being hampered by increasing resistance of the disease-causing Plasmodium parasite to anti-malarial drugs.

A new study led by the University of Oxford has identified genetic markers linked to resistance to the anti-malarial drug piperaquine. This new information can be used as a tool to identify areas where resistance is emerging and where current treatment strategies are likely to fail.

The international collaboration, including researchers jointly from the Wellcome Trust Centre of Human Genetics and the Wellcome Trust Sanger Institute, carried out a genome-wide association study on approximately 300 Plasmodium falciparum samples from Cambodia to study the genetic basis behind piperaquine resistance.

Piperaquine is used in combination with another anti-malarial drug, artemisinin, as a recommended frontline malaria treatment in many areas of the world. With parasites becoming increasingly resistant to artemisinin, increasing resistance to piperaquine as well could become a major public health problem.

Dr Roberto Amato, lead author of the study said:  ‘Our findings provide a tool to monitor in a rapid and cost-effective way the spread of resistance, ultimately helping public health officials deploying the most effective therapies.’

By studying the genome of the parasites infecting patients who were not responding to treatment, the scientists identified two markers linked with piperaquine resistance.  One way that anti-malarial drugs can work is by targeting the biological process that allows parasites to digest haemoglobin in the red blood cells; a family of proteins called plasmepsins plays a key role in this process. The scientists found that parasites with extra copies of the genes encoding two specific proteins of the plasmepsin family were more likely to be resistant to piperaquine. A second genetic marker linked with resistance was found to be a mutation on chromosome 13.

Professor Dominic Kwiatkowski, director of the Centre for Genomics and Global Health, and a lead author on the study, said: ‘These findings provide the tools needed to map how far this resistance has spread, looking for these molecular markers in parasites in Cambodia and neighbouring countries. This will allow national malaria control programmes to rapidly recommend alternative therapies where possible and where needed, enhancing treatment for patients, and helping towards the ultimate goal of eliminating malaria.’

The results of the study are published in the journal Lancet Infectious Diseases.

In the latest Oxford Sparks podcast, Oxford statistician Dr Jennifer Rogers explores the numbers behind recent alarming headlines linking processed meat with bowel cancer.

As podcast host Emily Elias notes, it was a bad day for meat eaters when the news broke, with The Sun opting for the headline 'Banger out of order – sausages and bacon top cancer list'.

Dr Rogers, Director of Statistical Consultancy at Oxford and a member of the Department of Statistics, says: 'You wouldn't believe how many maths teachers have said to me that bacon is banned in their house because of this 18% increase in bowel cancer. People just aren’t eating it anymore. I get so many people say to me, "Do I actually have to be worried?"'

The worries stemmed from a report released by the World Health Organization. Last year, bacon made its way on to a list that also includes arsenic, asbestos, alcohol and tobacco because scientists found a 'statistically significant' increased risk of getting bowel cancer.

Dr Rogers says: 'All "statistical significance" does is tell us whether or not something is a risk. It doesn’t really tell us anything about what that risk is – how big it is or how it affects us. There were lots of headlines saying that because bacon is on the same list as smoking that bacon and smoking were now just as risky as each other in causing cancer. And that is not true.'

Mass-produced factory bacon is made by injecting salty water and chemicals, including nitrates, into pork belly before it's cured.

Dr Rogers adds: 'If we look at lung cancer and smoking, for every 400 people we would expect four people to get lung cancer anyway, even without smoking. If you look at people who smoke 25 or more cigarettes every day, that goes up to 96 in every 400 people.

'Now compare that to what we get for bacon. Bowel cancer affects just over 6% of the population. So for every 400 people, you'd expect about 24 people to get bowel cancer anyway. Eating 50g of bacon every day increases this risk by 18%, which means if you were to take 400 people all who ate bacon every day, you would now expect 28 of those to get bowel cancer – an increase of four people in every 400, compared with 92 in 400 for smoking.

'So even though they both may cause cancer, to say they are both as risky as each other is probably pushing it a little too far.'

We should also note, says Dr Rogers, that people who eat lots of processed meat are perhaps less likely to live healthy lifestyles in general, which may contribute to the increased risk of bowel cancer. That's one of the problems with drawing conclusions from observational studies, as opposed to strictly controlled clinical trials, she adds.

While the WHO report did cause bacon sales to suffer a short-term hit, things seem to have recovered since the more measured reality around the initially startling headlines came to light.

Dr Rogers, who has her bacon sandwiches with red sauce, no butter and toasted bread, concludes: 'I think that sometimes numbers and percentages can be hard to get our heads around and it's easier just to say, "I'm not going to eat bacon."

'I was recently asked to comment on something else that had been added to the "gives you cancer" list – drinking really hot drinks. This time round, the newspapers were contacting statisticians before they wrote their headlines and articles because they'd learned a lesson from the bacon story.

'It turned out that you needed to be drinking really extreme temperatures of mate tea in South America – not the temperatures that we have our hot drinks at.

'It would have been really easy for the newspapers to say that drinking hot drinks gives you cancer – and that would have caused an uproar.'

Listen to the full podcast.

A pan-European team of researchers involving the University of Oxford has developed a new technique to provide cellular 'blueprints' that could help scientists interpret the results of X-ray fluorescence (XRF) mapping.

XRF imaging is used for a wide range of elemental analyses and has a number of medicine-based potential applications, including tracking and understanding diseases such as Alzheimer's, and the evaluation of heavy metal poisoning.

One barrier facing this technology has been the lack of cellular blueprints with which to compare the maps arising from XRF imaging. Now, researchers have been able to seal non-biological elements inside carbon nanotubes – tiny tubes 50 thousand times thinner than a human hair – to create 'nanobottles' that can be directed to individual cells to help create these blueprints.

The results of the study are published in the journal Nature Communications.

Dr Chris Serpell, a lecturer in Chemistry at the University of Kent who worked on the project while carrying out a research fellowship in Professor Ben Davis's group at Oxford, said: 'What's amazing about these findings is that the non-biological elements are toxic or gaseous, but they’re securely sealed within the nanobottles by just a single layer of carbon atoms. We're really pleased that this paper can showcase the biological potential of carbon nanotubes.'

Dr Serpell says that by using the contents of these nanobottles – such as barium, lead or gaseous krypton – as 'contrast agents', XRF imaging could become a much more widespread technique, providing insights into behaviours of proteins that use metals, and the role they have in health.

He added: 'Carbon nanotubes were once touted as a panacea to almost every technological problem, but in recent years people have become much more cynical about their utility. These results show that there are unique applications which are only possible using nanotubes – they are now moving towards realistic applications.

'Although it is at a very early stage in the pipeline, this technology can be expected to yield new insights into disease states and the effects of heavy metal poisoning, which can in turn lead to new healthcare technologies. A similar approach could also be used to deliver radioactive elements specifically to tumours for therapy, or to enhance other imaging modes such as MRI.'

Professor Davis, from Oxford's Department of Chemistry, said: 'This work was part of a training network across Europe known as RADDEL that was launched based on an earlier discovery that radioactive iodide could be packed into sealed tubes to be used in living animals.

'This new research has expanded on that finding, creating a spectacular system that encapsulates much more difficult elements and images these in cells using the rarely used technique of XRF. We have been able to use this method to see how the tubes find their way into different compartments in individual cells, controlled largely by how we chemically "decorate" those tubes.

'It's a striking example of something that would be tough to do by any other construct – to take a gas and "bottle" it before steering the bottle to one compartment in a cell so that you can use the gas for imaging.'

The study was a collaboration involving researchers from the universities of Oxford and Kent, Diamond Light Source, and Universitat Autònoma de Barcelona.

Have you ever noticed that liquid stays inside a straw when it’s held horizontally? Or that the same thing doesn't happen when you turn a glass on its side?

A team of researchers including Professor Dirk Aarts from Oxford University's Department of Chemistry has been investigating this phenomenon – one that's 'surprisingly difficult' to explain from a scientific point of view.

Professor Aarts worked with colleagues Carlos Rascón from Universidad Carlos III de Madrid in Spain and Andrew Parry from Imperial College London for the study, which is published in the journal PNAS. Professor Aarts said: 'We considered the following seemingly simple question: why does the liquid spill out when I hold a glass – say, of beer – horizontally, but stays in a straw when I do the same thing?

'This question is actually surprisingly difficult, especially when considering non-circular cross-sections of the capillaries, or tubes.

'For a liquid trapped between two parallel walls, and for a liquid trapped in a circular capillary like a straw, the answer is one that we would intuitively expect: the liquid wants to flow out because of gravity, but is trapped due to the surface tension.'

The 'capillary action' described here is the ability of a liquid to flow in narrow spaces, often in opposition to external forces such as gravity. For example, if you zoom in on the surface of water in a glass, you’ll see that it curves upwards by a couple of millimetres at the wall. This curve is known as the meniscus.

Professor Aarts said: 'The competition between gravity and surface tension leads us to the capillary length, which sets the height to which a meniscus will climb at a wall. Indeed, if the separation between the two walls is less than roughly the capillary length, or if a circular capillary has a diameter less than roughly the capillary length, the liquids will stay put. If not, the liquids will flow out.

'However, if you change the cross-sectional shape of the capillary – for example, making it a triangle – the situation may change completely, and for certain geometries the liquid may spill out at any length scale, well below the capillary length.

'We figured out how to calculate this behaviour for general cross-sectional shapes, although the actual numerical calculations, carried out by Carlos Rascón, took almost seven years to complete. One of the reasons for this was that the spilling out may occur via different pathways, and the crossovers between those pathways were hard to understand.'

The researchers were able to solve the problem by reducing it down to an equivalent two-dimensional problem, which is numerically more accessible. The paper shows how 'emptying diagrams' can be created by calculating the energy of the problem in 2D. As soon as the energy became smaller than zero, no 3D solution for the meniscus exists, and the liquid empties.

Professor Aarts added: 'The surprising result here is that a capillary may empty even at lengths much smaller than the capillary length. This has implications for any technologies where liquids are used or are present on small scales, such as microfluidics, biomedical diagnostics, oil recovery, inkjet printing and so on.'

What does the future hold for computing? Experts at the Networked Quantum Information Technologies Hub (NQIT), based at Oxford University, believe our next great technological leap lies in the development of quantum computing.

Quantum computers could solve problems it takes a conventional computer longer than the lifetime of the universe to solve. This could bring new possibilities, such as advanced drug development, superior military intelligence, greater opportunities for space exploration and enhanced encryption security.

Quantum computers also present real risks, but scientists are already working on new forms of encryption that even a quantum computer couldn't crack. Experience tells us that we should think about the applications and implications of quantum computing long before they become reality as we strive to ensure a safe future in the exciting new age of quantum computing.

A new animation, produced for NQIT by Scriberia, looks at how quantum computing could change our lives.