First-rate laboratory

These are busy times at the Swedish NMR Centre. Almost all of the magnets are completely booked up for the next few months, and researchers are coming from both the University of Gothenburg and Chalmers University of Technology as well as from other universities in Sweden. “We have one of the best NMR labs in Europe,” says Director Göran Karlsson.

The Swedish NMR Centre is located at the University of Gothenburg, but it is a national centre open to users from Sweden and the rest of the world. NMR stands for nuclear magnetic resonance, and it is used to explore the structure and composition of a molecule, among other things. Researchers come to the Swedish NMR Centre to use NMR spectroscopy to study everything from protein structures to various material properties and biomarkers in blood.

Lars Nordstierna use the NMR facilities frequently.

Lars Nordstierna use the NMR facilities frequently.

Lars Nordstierna is one of the researchers who uses the facilities regularly. He is an associate professor in surface chemistry at Chalmers and does research on soft material — that is, material that permits the movement of liquids or gases within it.

“You might think that this wooden table is a hard material, of course,” Nordstierna says, knocking on the table top in his office. “But if you pour water on it, the water will penetrate the table top. In other words, soft material is porous on a nanoscale, unlike metals, for example, which do not permit penetration.”

Knowledge of various materials’ properties is important for a number of different applications, everything from clothing made of cellulose from wood as a replacement for wool to pharmaceuticals in which the active ingredient to be released in the right place in the body makes up a small portion of the tablet. Nordstierna has had and has doctoral students who have studied the possibilities of making something other than paper out of cellulose from forests. The forest industry is eager to find new fields of application at a time when paper manufacturing is decreasing in Sweden. At the same time, many of today’s materials are produced in a way that is not good for the environment. “One example is cotton cultivation, which requires a lot of water and the use of lots of biocides,” he says.

Instead of using cotton, which also contains cellulose, to produce clothing, you can make clothing out of cellulose from the forest. Viscose is one such example. But in order for it to be used to a greater extent and be developed, we need to find a production process that has less of an impact on nature. This is where Nordstierna’s NMR technology comes in. “By studying cellulose fibres, we can find out more about their properties. And if we can understand the molecular level, we often can also understand the material’s macroscopic properties.”

NMR IS A common analytical technology, but there are a number of different methods that can be used within the field. To study cellulose, Nordstierna makes use of solid-phase NMR, in which the sample consists of a solid material instead of a liquid.

“Many researchers use NMR spectroscopy to investigate molecular structures, such as the structure of proteins. I myself am almost always familiar with the structure. Instead I want to find out how materials associate or aggregate with one another. Simply how cellulose molecules crowd together.”

Göran Karlsson is Director of the Swedish NMR Centre

Göran Karlsson is Director of the Swedish NMR Centre

Often methodology development has occurred within a certain application, but others then can use the same methodology to study something else. At the centre there is a concerted effort to develop methodologies, which takes place in close interaction with the researchers using the instruments.

“It’s important that we try to keep up with developments,” Karlsson says.

NMR TECHNOLOGY is not a clear-cut choice for all chemists to use. But for Nordstierna it is natural, because he has solid knowledge in this area from his time as a doctoral student at the Royal Institute of Technology. “I studied NMR spectroscopy for my doctorate,” he says with a smile.

He thinks the great advantages of NMR are the ability to obtain spectroscopic resolutions for all of the components in the sample. If you have ethanol and water in the sample, you can see all of the atoms in the result. You can see how quickly something moves and how different materials bind with one another.

“It’s easy to produce a result, but it can be difficult to interpret it in the right way since there are so many parameters to keep an eye on. Nor are there any ready-made approaches in many cases, but rather you have to feel your way forward to determine what an optimal measurement consists of.”

SINCE 2016 the Swedish NMR Centre has been part of SciLifeLab, a national institute for molecular biosciences. As far as the NMR Centre is concerned, the focus is on structural biology, chemical biology and metabolomics. The latter is an area of research that has come to the fore in the biosciences in recent years. Metabolomics can be described as a way of studying metabolites — that is, molecules in a biological sample — in a single chemical analysis. Anna Winkvist and Helen Lindqvist are two nutrition researchers at the Sahlgrenska Academy who work closely with the NMR Centre. They make use of metabolomics in nutrition research so they can better determine what people have eaten. With the aid of NMR spectroscopy, they can find various dietary markers in blood or urine.

“It is an extremely exciting technology for being able to objectively determine what people have eaten,” says Winkvist, a professor of nutrition.

OUR EATING HABITS traditionally have been surveyed by answering questions about what we have eaten. But such questioning always produces source errors. People forget what they have eaten, have difficulty estimating what size portions they have eaten and lie about their eating habits. In a method study that has just been carried out, a number of people ate breakfast in a food laboratory. One group was given a more protein-rich, British breakfast with ham, eggs and white beans, while the other group ate a carbohydrate-based Scandinavian breakfast with cereal and sandwiches. Subsequently they provided blood and urine samples, which were analysed at the NMR Centre.

Helen Lindqvist and Anna Winkvist make use of metabolomics in nutrition research.

Helen Lindqvist and Anna Winkvist make use of metabolomics in nutrition research.

Was it possible to distinguish between the different groups? Yes, it was, according to Lindqvist, a bioscience senior lecturer.

“However, we saw the biggest differences between those who chose to drink coffee and those who chose tea, which we had not anticipated initially.”

In this case the study was about diet choices that could be traced the same day in blood and urine, whereas other projects had to do with the effect of different dietary habits over a longer period. In another project, for example, the difference between omnivores, vegetarians and vegans was studied.

Previous methods that were used could only study one biomarker at a time. Analyses have been expensive and time-consuming. NMR spectroscopy has opened new opportunities for the research field. “Foods are complex and contain lots of different materials that can exert an influence in many different directions. The advantage of metabolomics is that we can include a great many materials at once,” Lindqvist says.

But while NMR spectroscopy makes it possible to generate a great deal of information, it also demands a lot of those who are to analyse all the data. Concurrently with the development of NMR technology during the past decade, bioinformatics also has made major strides. Being able to manage great quantities of data is becoming an important part of research. “We have had very good collaboration with the NMR Centre, and the development of our research has gone hand in hand with expansion of the centre,” Winkvist says.

THE NEXT STEP WILL BE using biomarkers to predict how well a certain type of treatment works for an individual patient. In this case it involves monitoring what effect a change in diet could have on an individual, which in turn should be able to increase the person’s motivation to alter dietary habits.

“Changing dietary habits is hard,” says Lindqvist. “It would help motivate us to change our habits if we knew ahead of time that a dietary change is likely to have a major impact.”

 NMR TECHNOLOGY HAS developed a great deal in recent years. Director Karlsson underscores the importance of disseminating information about what can be done with NMR technology, which can be used within a number of new fields. One example is sports science. University of Gothenburg sports researcher Ulrika Andersson Hall studies fat oxidation during exertion and also has used metabolomics to analyse blood. In her case the blood comes from elite athletes involved in endurance sports, and the purpose has been to see how this can foster the burning of fat. “This is the first time NMR has been used for sports research,” she says, “and we have had excellent collaboration and exchanges with one another.”

Ulrika Andersson Hall sees great development potential in science through use of the NMR Centre in the future.

Ulrika Andersson Hall sees great development potential in science through use of the NMR Centre in the future.

THE RESULT, WHICH HAS JUST been published, shows that burning of fat was not as high after fasting as after a previous exercise period, despite the fact that fasting is used by many today as a method of weight reduction. But she emphasizes that the results apply to top athletes engaged in endurance sports who need to develop their fat oxidation to be able to burn fat over long periods, and that is a major difference between them and other people.

“It has been interesting from a public health perspective to see if regular people also can develop fat oxidation — in case of disruptions in metabolism, for example,” says Hall, who sees great development potential in science through use of the NMR Centre in the future.

 Lars Nordstierna IS also somewhat of  an ambassador for NMR spectroscopy and is happy to share information about its different areas of application, both within his own university and as a representative in the steering committee for the Swedish NMR centre. “I feel that when you are skilled with a technique, you have a responsibility to inform other researchers about its potential. By discussing with others, you can also develop yourself and discover new opportunities.”

Swedish NMR Centre

There are seven spectroscopes at the Swedish NMR Centre. All are made up of superconducting magnets cooled using liquid helium and have advanced detectors for a wide range of applications.

The Swedish NMR Centre is to first and foremost support academic research locally, nationally and internationally and support education. As long as time and resources permit, it can support industrial research in Sweden. With funding from the Knut and Alice Wallenberg Foundation, the Swedish Research Council and SciLifeLab, special support is provided in the fields of structural biology, chemical biology and metabolomics.