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Bzhreport2010web.Pdf 2008–2010 REPORT REPORT RESEARCH AND EDUCATION IN MOLECULAR LIFE SCIENCESRESEARCH AND EDUCATION RESEARCH AND EDUCATION IN MOLECULAR LIFE SCIENCES HEIDELBERG UNIVERSITY BIOCHEMISTRY CENTER REPORT 2008–2010 Biochemie-Zentrum der Universität Heidelberg der Universität Biochemie-Zentrum BZH_Report_U1_RZ.indd 3 01.03.2011 10:26:40 Uhr Biochemie-Zentrum der Universität Heidelberg (BZH) Im Neuenheimer Feld 328 D-69120 Heidelberg Germany Phone: +49 (0)6221 54 4154 Fax: +49 (0)6221 54 5356 www.bzh.uni-heidelberg.de Director: Prof. Dr. Michael Brunner Editors: Prof. Dr. Irmgard Sinning Dipl.-Kfr. Catarina Vill-Härtlein Layout: Dipl.-Kfr. Catarina Vill-Härtlein Cover: Dipl.-Grafik-Designerin Anke Heinzelmann For a copy of this report please contact: Barbara Bohne (BZH-Administration) e-mail: [email protected] Introduction 4 Research Groups Michael Brunner 6 Elisabeth Davioud-Charvet 10 Tamás Fischer 12 Ed Hurt 14 Wilhelm Just 18 Martin Koš 20 Luise Krauth-Siegel 22 Johannes Lechner 24 Dimitris Liakopoulos 26 Walter Nickel 28 Heiner Schirmer 30 Irmgard Sinning 32 Thomas Söllner 36 Frank Weber 38 Felix Wieland / Britta Brügger 40 Teaching at the BZH 44 Facilities 46 Funding 50 Theses 54 Publications 56 Staff 64 Scientific Advisory Board 68 How to get to the BZH 71 Welcome to the BZH! Virtually all cellular functions are maintained by biological machines, which consist of macromolecular proteinaceous assemblies and nucleic acid/protein particles. The biogenesis and structure of such mo- lecular machines, as well as their function, regulation and interaction are in the focus of research at the Heidelberg University Biochemistry Center) (BZH). Biological processes studied at the BZH include the biogenesis of ribosomes, molecular mechanisms of protein translocation into the endoplasmic reticulum and the biogenesis of membrane proteins, the analysis of the machinery for vesicular transport and un- conventional secretion of proteins, as well as the spatial and temporal dynamics of molecular components of the circadian clock, which controls the day-night rhythm of cells. In addition, research groups are con- cerned with the biochemical characterization of plasmodia and trypanosomes. The BZH is a central institution for research and teaching. It was founded 1997 and today accommodates 14 research groups. Amongst these are 4 junior groups and a further junior group is presently being re- cruited. Altogether the BZH hosts about 200 scientific and non-scientific coworkers. More than 70% of the scientists are funded from external sources. Since its establishment the BZH has developed into a leading research establishment in the area of mo- lecular life sciences. A modern department structure with a flat hierarchy and complementary interests of research creates a lively atmosphere. The group leaders at the BZH pursue their individual research interests. These topics are, however, embedded into a general main topic, to develop synergies and to allow for a meaningful use of resources. Such synergies become evident in the research cooperatives that are hosted by the BZH. Felix Wieland is the coordinator of a large collaborative research center (SFB 638) and Thomas Söllner, who has a chair at the BZH since 2005, is the coordinator of an SFB/Transregio (TRR83) with participation of 17 research groups in Bonn, Dresden and Heidelberg. Research in molecular life sciences is subject to rapid technological progress and requires elaborate and usually extremely expensive machinery. The BZH has an excellent infrastructure, offering state of the art equipment in a wide range of leading-edge technologies. The center accommodates under the supervision of Britta Brügger a mass spectrometry facility for the qualitative and quantitative analysis of lipids, and Johannes Lechner leads a mass spectrometry facility for protein analysis. The BZH hosts under the direction of Irmi Sinning an automated facility for protein crystallization, which was supported by the CellNetworks cluster of excellence. Research groups within and outside of the BZH use this unit that is operated by Dr. Jürgen Kopp. Furthermore, facilities at the BZH offer confocal light-microscopy and fluorescence activated cell sorting (FACS). Finally, we are presently establishing a facility for electron microscopy. 4 Introduction The BZH is responsible for teaching Biochemistry in Medicine, Biology and Chemistry, and in particular en- gages in excellent training of the next generation of molecular life scientists with emphasis in Biochemistry. Annually, about 1000 students in the fields mentioned are being trained, and approximately 70 graduate students are working at the BZH on the average. For all graduate students participation is mandatory in an extensive BZH internal graduating program, which is coordinated with HBIGS, an international graduate school supported by the German Excellence Initiative. Within the framework of this program the gradu- ate students have the possibility of learning latest techniques and methods. Starting from 2012, the BZH will host a Bachelor and a consecutive Master program in Biochemistry, which is jointly offered by the Faculties for Chemistry and for Life Sciences. Due to its internal structure and imbedding into the research landscape in Heidelberg, the BZH is well set up to ensure also for the future excellent training of the next generations of scientists and to conduct research at an internationally competitive level. I hope this brochure captures your attention and inspires your view on our activities in research and teaching at the BZH. Prof. Dr. Michael Brunner Director, BZH Heidelberg, 30.01.2011 Introduction 5 1988 Ph.D. - University of Heidelberg, Germany 1989 - 1991 PostDoc - Princeton University and Rockefeller Research Laboratory, New York, USA (Prof. James E. Rothman) 1992 - 1998 Group Leader and habilitation - Ludwig-Maximilians- Universität München, Germany (Prof. Walter Neupert) 1998 - 2000 Professor - Ludwig-Maximilians-Universität München, Germany since 2000 Full Professor - BZH since 2010 Director - BZH Michael Brunner The Molecular Clock of Neurospora crassa Goal of clock-controlled genes (ccgs). Amongst the Circadian clocks are timekeeping devices genes directly controlled by the WCC are the that measure time on a molecular level and clock genes frequency (frq) and vivid (vvd). FRQ coordinate the temporal organization of glob- and VVD are circadian repressors that inhibit al gene expression. The endogenous cell-au- their own synthesis in negative feedback loops tonomous pacemakers are synchronized via by regulating the activity and abundance of the various signal transduction pathways with WCC in a rhythmic fashion. FRQ is in complex the exogenous geophysical 24 h day/night with the RNA helicase FRH and casein kinase 1a cycle. The molecular mechanisms underlying (CK-1a) and it inactivates the WCC by facilitating these phenomena are in the focus of our re- its phosphorylation by CK-1a and CK-2. FRQ search. also support accumulation of high levels of the WCC. FRQ is phosphorylated at more than 100 Background sites, which regulates turnover and function of the Circadian clocks are cell-autonomous oscillatory clock protein in complex manner. Several kinases systems that modulate rhythmic expression of and phosphatases - e.g. CK-1a, CK-2, PP1 and a large number of genes. In eukaryotes these PP4 – have been implicated in the control of its clocks are based on networks of interconnected phosphorylation status. transcriptional, translational and posttranslational feedback loops. Circadian clocks are synchronized The WCC is composed of the subunits WC-1 and with the exogenous day by environmental cues WC-2. WC-1 is a blue-light photoreceptor that such as light and temperature. In the absence of contains a flavin-binding LOV domain. Hence, the entraining cues clock-specific oscillations persist WCC can be activated by light. Light-activation with an intriguingly precise period that creates is required for synchronization of the clock with an endogenous robust self-sustained subjective external light/dark cycles. The activation of light- day-night rhythm of approximately 24 h. induced gene expression is a transient process. After an initial burst of transcription the levels of In the core of the Neurospora clock is the light-induced RNA decrease despite the presence transcription factor White Collar Complex (WCC), of continuous light and reach a steady state after which directly and indirectly activates transcription 1-2 h. The photoadaptation of light-induced gene 6 Michael Brunner expression is facilitated by Vivid (VVD), which hypophosphorylated FRQ rapidly shuttles is also a LOV domain containing blue-light between the cytosol and nuclei and equilibrates photoreceptor. between both compartments. In the course of the day FRQ is progressively hyperphosphorylated, Research Highlights which slows down its import kinetics but does not Circadian abundance and activity of FRQ and affect nuclear export. Accordingly FRQ gradually WCC accumulates in the cytosol and it is subsequently Recent fi ndings of our lab revealed the mechanism degraded in the course of the (subjective) night. underlying the circadian activity rhythm of the The circadian abundance rhythm of FRQ and WCC, which is the basis of timekeeping on a its progressive accumulation in the cytosol molecular level. We found that the subcellular facilitate rhythmic modulation of the localization distribution of FRQ and the WCC is highly and the activity of the WCC. FRAP analysis of dynamic
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