Ultrastructure

The ULTR group was built around Lode Wyns and Serge Muyldermans who started investigating biomolecular structures in the 80's. The initial focus was a biochemical and biophysical analysis of chromatin assembly and structure, necessitating major efforts in the acquisition of the appropriate technological tools, including protein & nucleic acid chemistry, genetic engineering, analytical centrifugation and spectroscopy. In 1989, the long fostered idea to start a true X-ray crystallography unit was turned into reality. Since then, the group has been growing steadily and presently comprises about 40 collaborators covering a broad range of scientific and technological expertise to study the general theme of Structure-Function analysis of Proteins. As is characteristic for so many protein crystallography groups, a number of protein systems are under study. On the one hand, they present strictly structural challenges, on the other hand they present associated functional and/or applied aspects. Protein carbohydrate recognition as demonstrated by lectins is one important theme. It documents the subtle interplay between a few dedicated protein loops leading to succinct specificities in otherwise very related proteins. Metal binding proteins are studied in the context of metal detoxification, TIM-barrels in the context of protein stability, and the CcdA/CcdB plasmid addiction system documents the very first protein structure blocking topoisomerase, a target for antibiotics. The Protein Engineering and Enzymology programme combines enzymology, spectroscopies, site directed mutagenesis and X-ray crystallography to study the principles of binding and catalysis, a research programme that was mainly developed by and through Jan Steyaert. The initial finding by Raymond Hamers of the existence of naturally occurring, functional heavy chain antibodies in camelids paved the way for a steadily growing group studying fundamental and applied aspects of Camelid Antibodies. Molecular biology, protein engineering and structural biology are being combined to investigate multiple aspects of these extraordinary antibodies. For the more applied part, various possibilities are being explored, including their use as enzyme inhibitors (industrial and pharmaceutical), diagnostics, (immune) receptor inhibition and anti-idiotype cancer therapy. More recently, protein stability and thermodynamics studies as well as NMR work are being included in several of the ongoing projects.