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New Centre of Excellence – inflammation research:

When the body’s line of defence becomes the enemy

What happens when the human immune system – the body’s own defence mechanism – is transformed into the enemy? This is the puzzle researchers worldwide are currently working to solve. A new Centre of Excellence in Trondheim has taken on the task of providing some of the essential pieces.

Cancer, obesity, type 2 diabetes, Alzheimer’s disease, arteriosclerosis, inflammatory bowel disease and allergies. More and more people in the West are becoming affected by these disorders.

While these afflictions differ widely, they also have certain characteristics in common. A condition known as chronic inflammation may be a factor behind them all. The current search for common characteristics is a topic of major interest to the researchers around the world.

“If we find what they have in common we will also have the key to developing treatments of great significance for these disorders,” states Dr Terje Espevik, director of the new SFF Centre of Molecular Inflammation Research (CEMIR) at the Norwegian University of Science and Technology (NTNU) in Trondheim.

Photo: Geir Mogen/NTNU Our strength lies in working across traditional boundaries, says Dr Terje Espevik (Photo: Geir Mogen/NTNU) From good to bad

Normally, inflammation is beneficial to the body. It is a vital process in fighting and healing infections. But what happens when inflammation fails to heal and leads to a chronic disorder instead?

One of the reasons why many researchers are interested in the topic is that obesity has become such a major problem in many parts of the world. A recent discovery has shown that fat tissue can set off inflammation which, in turn, is associated with the development of type 2 diabetes.

Macrophages – the body’s rubbish collectors

Early in the 1980s, Jon Lamvik, a professor at NTNU, began studying macrophages. These are the “rubbish collectors” of the body, devouring foreign cells such as bacteria.

For example, a splinter containing bacteria pierces the skin of an individual’s finger. The tissue becomes red, warm and sensitive, indicating that the area surrounding the splinter has become infected. At this point, the macrophages – a type of cell involved in innate immune responses in humans – discover what is going on. Upon detection of the infecting bacterium, the macrophages send distress signals (cytokines) to alert and attract more immune cells to help to clear the infection. This also triggers the repair processes that help to heal the sore. Sometimes, however, these macrophages are unable to repair the damage. This may occur when the macrophages do not remove all of the distress signals and the repair activity evolves into a chronic condition. This is what happens in cases of arteriosclerosis, type 2 diabetes, allergies and autoimmune disorders such as arthritis.

In the mid 80’s Terje Espevik and colleague Anders Waage discovered that the signalling molecules can have a deadly toxic effect on the body when they amass in excess. In those cases, it is not the bacteria that pose a threat, but the defensive response of body’s own immune system.

This discovery, along with the characterisation of a signalling molecule called tumor necrosis factor (TNF), has contributed to a whole new understanding of inflammation and blood poisoning. These efforts have made Dr Espevik one of Norway’s most cited researchers.

Wanting to help patients

Although the activities being carried out at the current SFF centre primarily consist of basic research, Dr Espevik and co-director Trude Helen Flo make it clear that the centre’s primary objective is to lay the foundation for developing potential therapeutic and diagnostic tools, and thus for helping patients. Understanding inflammatory responses is important for health, including global health, and greater insight into how inflammatory processes are initiated and regulated will contribute to the development of new drugs and vaccines.

Thirty years ago, Dr Espevik put a lot of effort into finding industrial partners who could help to develop medication to counter the damaging effects of TNF. Unfortunately, he lost out at the finish line. Today, there is a treatment for arthritis on the market that eliminates TNF and reduces the inflammation it induces. However, there is still much about these processes scientists do not yet understand.

Photo: Geir Mogen/NTNU THE BODY’S OWN RUBBISH COLLECTORS: Marie Hjelmseth Aune and Harald Husebye, postdoctoral fellow and researcher, respectively, at work at CEMIR. The image on the screen shows a cell (the nucleus in blue) from the immune system, a macrophage, specialising in attacking infection. (Photo: Geir Mogen/NTNU)

Inspired by NTNU colleagues

Money is important, but the ability to carry out comprehensive research for many years to come is even more critical, as is status as a Centre of Excellence.

“At present we are hiring exciting new staff for postdoctoral positions and fellowships. And we have the luxury of picking and choosing the best from among highly qualified candidates, both Norwegians and researchers from other countries.

The CEMIR centre and the Centre for Neural Computation (CNC – also an SFF) are close neighbours in Trondheim. The people at the CEMIR centre are clearly inspired by the work of CNC’s husband-and-wife team May-Britt and Edvard Moser.

“Their work has resulted in a great number of findings that may prove useful to us. For example, we have copied their interdisciplinary model by hiring six top-notch international researchers from different subject fields, each in a 20 per cent position, and letting them enter into binding collaboration among themselves. Three of them are from the US, one from Germany and two from Oslo. They will also be in charge of three doctoral-level courses that the centre will be providing.”

Norwegian David vs. international Goliaths

In this field of research, it is important to establish your own niche, preferably an area not already subsumed under the activities of the international giants, Dr Espevik explains.

“Our strength lies in working across traditional boundaries. For example, we have been unique in adopting imaging techniques typical to cell biology research and introducing these into the world of immunology. We were among the first in the world to do this. The major research groups in this field have been using mice as animal models, which is much more expensive. This is something we were unable to take part in before, but now our collaboration with researchers abroad has made these models available to the centre.

Technology from the field of cell biology has already helped the centre’s researchers to understand more about the immune system. Building on its status as an SFF, and starting with close to 100 employees located together in Trondheim this fall, the prospects of unlocking even more parts of the mystery are good indeed.

Centre for Molecular Inflammation Research (CEMIR)
  • Objective: To gain a greater understanding of the mechanisms triggering inflammatory responses in the human body in order to develop diagnostic methods and treatments for illnesses where inflammation plays a key role. 
  • Centre director: Terje Espevik. Co-director: Trude Helen Flo
  • Annual allocation from the Research Council of Norway: NOK 16.5 million 
  • Total person-years: 30
  • Number of doctoral degrees planned: At least 30 postdoctorates.

www.ntnu.no/cemir

 

Written by:
Siw Ellen Jakobsen/Else Lie. Translation: Glenn Wells/Carol B. Eckmann
Published:
12.09.2013
Last updated:
19.09.2013