BIENNIAL REPORT 2000-2001 BIOZENTRUM DER UNIVERSITÄT BASEL Biozentrum Basel Klingelbergstr. 50 – 70 CH-4056 Basel Switzerland Tel.: +41 (0)61 267 2111 Fax: +41 (0)61 267 1712 E-mail: [email protected] www.biozentrum.unibas.ch A printed copy of this report can be obtained via the Chairman's secretary at the above address or e-mail. An online copy is available on our homepage. Cover The eyes shown on the cover belong to the people who have worked at the Biozentrum at the end of 2001. The list of people is not restricted to scientists only but also includes the members of the administration as well as the various internal services and craftsmen. This is to qualify the Biozentrum as a “lively house”, which for best function needs the input of all its “inhabitants”. Creation, design and layout by Veit Goder Impressum Design and layout Anka Stark Edited by Debbie Neyer, Anka Stark Portraits and imaging support Vreni Grieder, Annette Roulier, Ingrid Singh Exposure and printing Alban Druck Basel CONTENTS PREFACE 5 TEACHING ACTIVITIES 6 DIPLOMA THESIS 7 DOCTORAL DISSERTATIONS 9 ADVISORY BOARD 12 DIVISION OF CELL BIOLOGY 13 Induction and patterning in Drosophila melanogaster (M. Affolter) 14 Neuronal circuits formation in the developing spinal cord (S. Arber) 16 Master control genes in development and evolution (W.J. Gehring) 18 Processing and editing of eukaryotic messenger RNA precursors and of transfer RNAs (W. Keller) 20 DIVISION OF STRUCTURAL BIOLOGY 24 Structure-based functional analysis of proteins and their supramolecular assemblies (U. Aebi) 25 Membrane protein structure and function (A. Engel) 29 High resolution NMR of biological macromolecules (S. Grzesiek) 33 Protein X-ray crystallography (O. Mayans) 36 Crystallography of membrane proteins (T. Schirmer) 37 Macromolecular interactions in coiled coils, protein ligand complexes and protein de novo design (P. Burkhard) 39 Odds and ends of actin structure and function (C.-A. Schönenberger) 41 DIVISION OF MOLECULAR MICROBIOLOGY 42 DNA restriction and modification (T.A. Bickle) 43 Molecular mechanisms of microbial pathogenesis: the Yersinia paradigm (G. Cornélis) 45 Molecular and cellular basis of bacterial persistance in the infected host (C. Dehio) 48 Differentiation in Streptomyces - multicellular development in a procaryote (C.J. Thompson) 50 Temporal and spatial control during the bacterial cell cycle (U. Jenal) 54 Genomics as information basis for investigation dynamics of growth and nuclear migration in fungi (P. Philippsen) 57 DIVISION OF BIOCHEMISTRY 61 Signal transduction and control of cell growth (M. Hall) 62 Membrane traffic in yeast (H. Riezman) 65 Membrane protein topogenesis and intracellular protein sorting (M. Spiess) 68 Modulators of steroid hormone signaling (A. Kralli) 71 DIVISION OF BIOPHYSICAL CHEMISTRY 73 Extracellular matrix, cell adhesion and oligomerization (J. Engel) 74 The mechanism of protein folding (T. Kiefhaber) 76 Molecular functions and mechanisms of membrane active agents (G. Schwarz) 79 Membrane interactions and in vivo magnetic resonance (J. Seelig) 80 Membrane barriers: passive diffusion and active transport (A. Seelig) 83 BIOZENTRUM BASEL DIVISION OF PHARMACOLOGY/NEUROBIOLOGY 85 Protein traffic in the secretory pathway (H.-P. Hauri) 86 Chair for Applied Pharmacology (K.G. Hofbauer) 88 Neural substrates of emotions (Andreas Lüthi) 90 Subcellular, cellular and network pacemakers in the sleeping and epileptic brain (Anita Lüthi) 92 Molecular mechanisms of diversity in response to drugs and chemicals in man (U.A. Meyer) 94 Synapse formation and neuromuscular diseases (M. Rüegg) 98 Thermodynamics and kinetics of energy conversion (D. Walz) 102 DIVISION OF BIOINFORMATICS/SIB BASEL 103 Meiotic development in yeast (M. Primig) 104 Protein structure bioinformatics (T. Schwede ) 106 THE LIFE SCIENCES TRAINING FACILITY (M. Primig) 108 PROTEIN CHEMISTRY (P. Jenoe) 109 ZMB (CENTER OF MICROSCOPY OF THE UNIVERSITY OF BASEL) Service, teaching, and development of instruments (M. Dürrenberger) 111 MYOCONTRACT PHARMACEUTICAL RESEARCH LTD. Friedreich Ataxia (T. Meier) 114 CORE FACILITIES 116 5 PREFACE PREFACE 30 years Biozentrum! In December 2001 the Biozentrum celebrated its 30th anniversary with an evening for the general public, a 2-days scientific symposium and, last but not least, a party-night for the present and previous members of the Biozentrum. These events attracted a large number of participants, somewhere between 500-800 people each, including many colleagues from other universities and from the industrial neighborhood. 30 years ago, at a time when biology was still considered a “soft” science and chemistry and physics were the leading “hard” sciences it was a courageous and visionary decision to create a new building with some 20 professors and a yearly endowment of about 25 Mio CHF devoted exclusively to biology. A new name was created, the “Biozentrum” and for the next 15 years the “Biozentrum” would remain the first and only such center world-wide. The success of the Biozentrum, gaining high international visibility in only a few years, attests primarily to the scientific quality of its research groups. This was helped, however, by implementing two new concepts. The first was to bring together under one roof apparently unrelated fields such as chemistry, physics, microbiology, cell biology, biochemistry, and pharmacology and to create an amalgam of these sciences with biology. The second was the development of a new curriculum organized around 2 month courses devoted to one topic only. Even though there was no established “market” for such an education and though it was initially unclear where the students would finally end up in their professional life, this curriculum became extremely popular. Some 550 students have by now received their diploma. In addition, more than 600 post docs have been trained. According to our last count more than 300 former students and post docs hold academic positions worldwide. The 30 year anniversary has finally marked a step into the future. During the last 3 years a large part of the original faculty has retired, but 12 new faculty members could also be hired at an average age of 38. New blood is circulating in the arteries of the Biozentrum, fostering scientific research and education at the highest possible level. Joachim Seelig Chairman Biozentrum April 2002 5 BIOZENTRUM BASEL TEACHING TEACHING ACTIVITIES The Biozentrum educates scientists at the diploma, doctoral, and postdoctoral levels. The particular advantage of education at the Biozentrum is its direct integration into research. All lecturers are active, grant-holding scientists. The ratio of lectureres to students is also ideal and ensures an optimal support for every student during their studies. The Diploma in Biology Based on this education scheme, the two separate curricula called Biology I and Biology II taught by the Department of Integrative Biology and the Biozentrum were brought together in Fall 2000, to form the new curriculum in biology. This takes four years to complete and is taught by lecturers from both Departments. During the first two years of basic studies, the students receive the essential grounding in mathematics/ statistics, physics, and chemistry as well as introductory courses in biology. In addition, they are trained in ethics and attend optional courses in biology as well as non-biological subjects. After having completed the basic studies, the students must choose either molecular biology or organismic biology to be the main focus of their further studies, because the content of the third year, which consists of block courses lasting several weeks each, is determined by this choice. The block courses provide theoretical information which the students then turn into practice in the laboratory or in the field. During the fourth and last year of the studies, the student works on his diploma thesis which is roughly equivalent to a Masters thesis in Anglo-Saxon universities. It is actually the student’s real introduction into research. At the Biozentrum, the diploma students can specialize in biochemistry, bioinformatics, biophysics, developmental biology, genetics, immunology, microbiology, structural biology or cell biology. A complete list of the diploma theses completed during the report period can be found on page 7. The interaction between the students and the lecturers is additionally supported by the so called career mentoring: at the beginning of their studies, every student is assigned to a certain lecturer, which implies an early contact between researchers and students. These lecturers, the career tutors, are the students’ contact person and personal advisors during the entire duration of their studies. The PhD program The Biozentrum also offers a doctoral degree studies. Besides the work on his/her dissertation, the student must attend lectures that take place in regular cycles within a time frame of 2 – 3 years. The current cycles cover molecular genetics, membranes, cell biology, biological systems, macromolecules, biotechnology, plant cell biology, molecular biology, virology/molecular medicine, neurosciences, and immunology. The work on a dissertation normally lasts about 3 years. After approval of the dissertation by the Science Faculty of the University of Basel, the studies are terminated with a detailed oral examination. A complete list of the dissertations completed during the report period can be found on page 9. Seminars at the Biozentrum The Biozentrum has a formal seminar series, the “Biozentrumsseminare”,