GRANT. Professor Gunnar C. Hansson, world leading scientist in the field of mucus and mucins, has received the prestigious ERC Advanced Grant from the European Research Council. His research group at the University of Gothenburg is behind a number of revolutionary discoveries on the protective mucus layer in the intestines and airways. Goals are set on new ways of treating a number of diseases, such as cystic fibrosis and ulcerative colitis.
The grant from ERC provides the research group with a total of EUR 2.5 million over five years, just over SEK 23 million.
Ten years ago, researchers believed that the bacteria in the intestine were in direct contact with human tissue and that the immune system was able to differentiate between the normal bacteria and disease causing ones s. Gunnar C. Hansson and his research group revolutionized the picture completely by showing that there is a protective bacteria-free mucus layer separating the bacteria and the intestinal wall made up of proteins called mucins.
A whole new way of thinking
“Normal mucus is not visible as it mainly consists of water. Our discovery changed all international research and now, the protective mucus layer that we discovered is always included in illustrations that describe how the intestine works,” says Gunnar, who heads a large research group in the Department of Medical Biochemistry and Cell Biology at the University of Gothenburg.
On the table in his office lies a pile of plastic models of parts of mucins that play different roles in ensuring that the mucus layer functions correctly. The 3D printer that is used to create the models is close by.
“A 3D printer was probably the best investment I made last year. It has helped us understand a lot of functions of the molecules and how they connect to one another,” says Gunnar, and picks up two of the plastic models to show what he means,
“When we have the molecules in our hand, it is not difficult to realize that there is only one natural way for them to fit together, namely, like this. Later studies showed this to be correct.
The research group has been able to describe how the protective mucus layer is regenerated and maintained. The mucins are made by a special cell type that also stores these long proteins in a very well-packed way until they need to be secreted, something that explains how mucins can expand 1,000-times and cover large areas. Recently, the group was able to show that a particular enzyme is needed for the mucins to be able to be released from these cells. At the same time, they also proved that ulcerative colitis, an inflammatory disease of the intestinal mucus, is related to the inner mucus layer not functioning properly.
In the past few years, the group’s research area has come to include also the airways including diseases such as chronic obstructive lung disease (COPD) and cystic fibrosis. Cystic fibrosis is an uncommon disease, where the mucus is thicker and stickier than normal. In healthy persons, the mucus and mucins slowly move upwards in the trachea by the help of cilia, but in cystic fibrosis they do not.
“Because the mucus sits still, bacteria cannot be ´transported away and the patients continuously suffer from chronic lung infections. We have shown that the lack of bicarbonate in connection with the release of the mucins is an important defect. The mucins do not unfold correctly. Knowing this should make it possible to affect and normalize the mucus that is made,” says Gunnar, who at this point in time does not have a ready answer on how this information can be turned into a new treatments.
“In the laboratory, we can do trials that show that bicarbonate can normalize the release of mucins, but how that can be practically handled in the clinic, is another question. Moreover, we need to better understand the significance of calcium ions and how the mucin function is disrupted. These are a few of all of the research questions we are continuing to work on.”