During his PhD studies, Rune Kidmose investigated how a particular part of the innate immune system in humans – the complement system – is activated when pathogenic microorganisms enter the body.

When this takes place, the microorganism is detected by the immune system, and a protein called C4 is cleaved into two parts by the enzyme MASP-2, which is also a protein. When C4 is cleaved into two parts, a long chain reaction involving many other proteins is initiated, and this ultimately results in activation of the immune system.

Rune Kidmose succeeded in capturing and trapping the C4 and MASP-2 proteins together in a crystal while the MASP-2 was actually about to cleave C4 into two parts. By exposing the crystal to intense X-ray radiation, Rune Kidmose was able to construct a three-dimensional model of what was inside the crystal. This 3D model was able to reveal right down to the atomic level exactly how MASP-2 binds to and cleaves the much larger C4 protein, and thereby how the immune system is activated. This make the subsequent development of inhibitors easier for this part of the immune system, which is desirable in certain acute and chronic disease conditions such as diabetes and arthritis, where unwanted inflammatory reactions play an important role.

The PhD degree was completed at the Department of Molecular Biology and Genetics, Science and Technology, Aarhus University.

Time: Thursday 21 February 2013 at 14.15
Place: Lecture Theatre D2, Department of Mathematics
Title of dissertation: Structural basis for the activation of human complement component C4
Members of the assessment committee:
Professor Christine Gaboriaud, Jean-Pierre Ebel Institute of Structural Biology, Grenoble, France
Associate Professor Søren Hansen, Department of Cancer and Inflammation Research, University of Southern Denmark
Associate Professor Ditlev Egeskov Brodersen (chair), Department of Molecular Biology and Genetics, Aarhus University
Main supervisor:
Professor Gregers Rom Andersen, Department of Molecular Biology and Genetics, Aarhus University
Co-supervisor:
Senior Associate Professor Lars Sottrup-Jensen, Department of Molecular Biology and Genetics, Aarhus University
Language: The dissertation will be defended in English

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1521, room 112, 8000 Aarhus C.