Georg Kraal Van Loghem Laureate 2011

kraal.pngVan Loghem Laureate Georg Kraal: “I belong to the visual type”

Prof. dr. Georg Kraal of the VU Medical Center in Amsterdam is this year's Van Loghem Laureate. He is committed to his research area of immune regulation. “As a researcher, I have no direct intention to develop medicines or cure diseases. This being said, it is clear that the mucosal immune system is vital to human health and it would be fantastic when our research could contribute to curing for instance Crohn's disease.”

Georg Kraal was born in 1950 in Amsterdam, the city of his alma mater, the VU University. Kraal studied biology. “I belong to the visual type, I have always been fascinated by the shape and structure of things”, he says. “By studying this, we understand the functioning of organisms. Biology gave me the perfect alibi for endless hours of determining the relation between form and function” During his study acquaintance with the electron microscope was a revelation to him. “To be able to see things that used to be invisible to the naked eye, I couldn't get enough of it.” Tissues were his special area of interest and his PhD study was in the field of histology. “I researched the functioning of the immune system in organs, such as the spleen. I isolated cells from tissues to study their interaction.” He then went to Stanford University where he focused on lymphocyte migration using monoclonal antibodies. “I made monoclonal antibodies to study the localisation of lymphocytes: why do different lymphocytes migrate to different places in the body? Why do certain populations migrate to the skin and others to the intestines and what is the molecular basis for these differences?”

Mucosal immune system
Working at Stanford as a post-doc was a privilege, says Kraal. “It's a researcher's paradise. The budgets are considerable and colleagues are extremely driven. I found it inspiring.” When he left for Stanford, he had a job offer at the VU in his pocket, a rare honor back in those days. After a few years in California Kraal decided to accept the offer and to become a teacher and a researcher in immunology and molecular cell biology. Up to this day, that is his playing field. His research group focuses on the complex task of unraveling the mucosal immune system. “On the one hand, it needs to ignore the continuous presence of harmless antigens that enter our body via the airways and the intestines. On the other hand, swift action is needed against pathogens. How is this system regulated?” Tolerance of the mucosal immune system depends on an interplay between local factors present in the mucosal epithelia and draining lymph nodes. These factors instruct the cells of the immune system. Small perturbations in the micro-environment of the mucosa or the lymph nodes can lead to excessive inflammation. “My research group tries to understand the many factors that regulate the immunological tolerance and that maintain the right populations of myeloid and lymphoid cells along the mucosal epithelia. In addition, we focus on their situation in the intestines in order to study the effect of chronic inflammation on the mucosal immune system.”

Fundamental research
The work at a university medical center is translational by its very nature. But, says Kraal: “I am a researcher and I strongly believe in the value of fundamental research. Without a strong basis we get nowhere.” His research is therefore not directly aimed at developing medicines or curing diseases, but Kraal keeps his eyes open for possible applications. “The mucosal immune system is vital to human health. It directly concerns the functioning of the body. And if we could find ways to modulate the immune system and contribute to curing for instance Crohn's disease, that would be fantastic. At this moment chronic inflammatory diseases such as Crohn’s disease and Rheumatoid arthritis cannot be cured. Treatment of patients consists of battling the symptoms of inflammation. In Amsterdam we try to translate our knowledge to human disease, to explain how inflammation is regulated at the cellular and molecular levels. We investigate how we can apply this knowledge to develop vaccination strategies for use in mucosal vaccines.”

Kraal intends to make full use of the possibilities offered by technology. “New technology now enables us to photograph and analyse thousands of cells per minute. With two-photon laser scanning microscopes we can study living tissues, to actually make real-life recordings from cells in tissue. We like to apply this technology to the gut epithelium, consisting of cells that are strongly connected to each other by proteins. In case of inflammation they tend to let each other go. Why do they do that? At what moment and under which circumstances? That is what I would love to see with my own eyes. If we understand the mechanism, we can try to use this in approaches to fight inflammation.”

On another level technology also has an impact. “Over the past thirty years, tool kits have been developed that make it a lot easier for researchers to obtain and standardize results. Craftsmanship has become less crucial to success. Many researchers can do the same. This enhances competition: you have to be the first to come up with an idea, you have to keep on renewing yourself. Sometimes this requires a detour. And although in general it is wise to follow a steady course, I enjoy the beautiful panoramas a detour can bring.”

The problem is to get funding for it. But not only for interesting detours; in general funding has become a problem, Kraal underlines. “It worries me. The cost of research grows because of new technologies and regulatory issues, but funds are scarce. This situation is aggravated by the current economic crisis. This goes at a national level, but also within Europe. Funding can still be found for large studies. But for smaller, specific studies it is much harder. Creativity suffers from this. I hope this problem can be countered.”

Georg Kraal is honored to be this year's Van Loghem Laureate. The author to acclaimed  publications (in e.g. Nature Immunology, the Journal of Experimental Medicine and the Journal of Immunology) takes his hat off to his predecessors. “It's almost a burden to step into the footsteps of revered scientists like Van Loghem and Van Rood. I'll do my best to live up to this!”

interview by Alida Wolthuis

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