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Bijvoet Center 20 Years A quest for structure and function Visions behind the Bijvoet Center years A quest for structure and function Visions behind the Bijvoet Center Bijvoet Center for Biomolecular Research 20 years Welcome by the scientific director Welcome emphasis on structural biology. The initial strengths of from our university, the science faculty, and Dutch funding tools to increase cross-fertilisation between the Bijvoet the Bijvoet Center were in the main its developments in agencies. Most of the plaudits and thanks however, should Center’s embedded groups. Naturally we also ensure that protein NMR, X-ray structure elucidation and carbohydrate go to the young researchers from the Netherlands and our students not only experience the best that locally biochemistry. However, significant extensions and changes abroad, who find the Bijvoet Center a fertile ground for based research has to offer, but provide opportunities for in direction have been part of the Bijvoet Center’s the initial part of their careers either as undergraduate and international exposure. We have expanded our core base development over the years. Small molecule X-ray graduate students or as postdoctoral fellows. of quality-teaching and research by inviting internationally crystallography has evolved, and been extended, to include renowned researchers to Utrecht and we also encourage serious efforts in protein crystallography with now first- In the years ahead we will have to anticipate the ever students to visit international research groups and rate international reputation. Although the stronghold expanding possibilities of new technologies and the new conferences. Utrecht University’s educational structure in carbohydrate chemistry has been reduced in recent opportunities they provide to study the detailed biology is dynamic and the position of institutes such as the years, related efforts in the Medicinal Chemistry group of cells at the molecular level. We will increasingly Bijvoet School is, therefore, often subject to change. The have surfaced to balance this. The Mass spectrometry understand the intricate play of the biomolecules present Bijvoet School has shown a ready ability to adapt to these The Bijvoet Center for Biomolecular Research department has seen a huge expansion in infrastructure in the cell which is required for biological function. This requirements for change by holding to the single premise of (Research Institute and Graduate School) celebrates and expertise and is now a world-leading research group, expansion of our knowledge of protein networks and maintaining excellent standards of research and education its 20th anniversary in 2008. both in proteomics as well as in macromolecular mass protein-small molecule interactions allow for new areas throughout these shifts. This is, I believe, testimony to the fact that, building on the spectrometry. An entirely new research line that has been such as molecular system biology and chemical biology foundations led by the pioneering scientific director Hans incorporated in recent years is that of protein folding, both to come within reach. Unique for the Bijvoet Center, with In this book, published to celebrate our anniversary, you Vliegenthart and the preceding Scientific Director Rob in vivo and in vitro as performed in the Cellular Protein only a few comparable initiatives in Europe, is the powerful will find interviews with some of the current and former Kaptein, we have established an institute of lasting value. Chemistry group. There is strong cross-fertilisation between combination of the structural biology expert facilities Bijvoet Center participants. We hope this will provide As the Bijvoet Center we have been able to preserve quality this group and the structure technology oriented groups in in crystallography, microscopy, mass spectrometry and you with a flavour of our activities and will give you a in the changing scientific climate. The Center is adaptable protein NMR, crystallography and mass spectrometry. The NMR, next to the functional molecular biology expertise snapshot of the Bijvoet Center as experienced by the people to new developments in science and scientific-funding. In Faculty of Science has always had strong representation groups. Holistically, we are optimally geared-up for the responsible for the research and education. Many of the comparison to other scientific institutions, 20 years perhaps in biomembrane related research, both within the Bijvoet comprehensive analysis of cellular biology at the molecular interviewed researchers have addressed questions on seems not that old, but in the current age with ever growing Center and the Center for Lipid and Membrane Enzymology. level starting from molecular structures, via protein- their personal motivation, and their scientific dreams and demands for administrative restructuring of universities, The recent merger of these two institutes has been a networks and protein-protein/protein-DNA and protein/ ambitions. I sincerely hope you enjoy reading it at the time their faculties and departments, and the seemingly constant natural process and has further extended the cross- membrane interactions, through to sub-cellular localisation of our anniversary or in the years ahead, to see how we introduction of new fashionable names, an institute that fertilisation of research in all groups of these two centres. and cellular function. have lived up to our dreams. celebrates its 20th birthday is quite exceptional. With these changes, the Bijvoet Center has now emerged from its teenage years and has matured into an important Concomitantly, we seek to constantly rejuvenate our Sincerely yours, The Bijvoet Center in its first 20 years has established itself centre for molecular structural biology in Europe. Bijvoet School activities in order to further enhance the 2 as a stronghold for biomolecular research with a special All this has only been possible by continuous support education of our talented students and introduce further Albert J. R. Heck | Scientific Director Bijvoet Center 3 Content Interviews with Group Leaders 5 Piet Gros - Crystallography: a big Aha-Erlebnis 6 Marc Baldus - The right mix of techniques 11 Ineke Braakman - Understanding protein folding 15 Gerrit van Meer - The accidental lipid guy 20 Alexandre Bonvin - Solving 3D puzzles 25 Stefan Rüdiger - Unboiling an egg 29 Antoinette Killian and Roland Pieters - Fundamental science for medical applications 34 Rolf Boelens - Magnetised by protein-DNA interactions 39 Joost Holthuis - Synthetic dream 43 Albert Heck - Riding the back of a protein 47 Interviews with Junior Researchers 52 Michael Hadders and Kristina Lorenzen - Being a PhD student at the Bijvoet Center 53 interviews Chris Arnusch and Klaartje Houben - Life as a postdoc at the Bijvoet Center 59 Ewald van den Bremer - The opportunity of a lifetime 66 Group leaders Interviews with Advisors 71 Piet Gros Ad Bax - Sharing the same coffee machine 72 Marc Baldus Emmo Meijer - PhD students and postdocs are the real workforce 77 Ineke Braakman Ivo Ridder - A Center of Excellence ‘avant la lettre’ 81 Gerrit van Meer Bas Leeflang - The burden of paperwork 86 Alexandre Bonvin Hans Vliegenthart - The vision behind a successful institute 90 Stefan Rüdiger Antoinette Killian & Roland Pieters Bijvoet, a name to be proud of! 96 Rolf Boelens Joost Holthuis Illustrations used in this book: Chemistry Research Day 19 April 2007 ‘Imaging and Imagination’ Albert Heck 5 Bijvoet Center for Biomolecular Research 20 years Crystallography: a big Aha-Erlebnis A crystal structure gives us very valuable insights. It gives working together, which evolved long before antibodies. an overall 3D picture of the molecules we are interested Antibodies form an adaptive immune system, whereas in. Essentially, a protein molecule is a very mechanical, the complement system is a primordial, innate immunity architectural thing in most cases. The function of a system that recognises foreign cells. Flies, for example, do protein depends on its shape. Knowing the shape, if not have antibodies, but they have similar proteins to the you will the structure, provides a framework for complement system in order to defend themselves. understanding the protein’s biochemical data. Once you The complement system was discovered in 1902 and are able to see the structure it is often an ‘Aha-Erlebnis’, consists of thirty to forty proteins that are able to one is able to put the biochemical insights together in recognise and kill bacteria. These proteins are generally one big picture and then start to understand how the very large molecules. We want to know how they work molecule works. together to discriminate between foreign cells and our Protein crystallography involves many disciplines. Initially, own cells, and how this system is activated. it requires a lot of molecular biology and biochemistry The process starts with recognition, which is basically the preparation (making proteins and testing their functions) binding of molecules. The next step is called “activation”. and then you arrive at the unusual step: growing a crystal. Understanding the molecular processes of activation is a interviews The next steps are all physics and mathematics. We use particularly structural question. In many cases activation, X-rays to shine on the crystal and collect the diffracted and regulation, means there is a complex formation of Group leaders X-ray beams. From the X-ray diffraction data we can different proteins and these proteins actually change then compute the information back
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