Kapitel 2 Baumeister 1 Einbindung FRISBY Life Sciences in the 21st centuray will become typically multidisciplinary and oriented towards the exploration and exploitation of entire systems. The University of Freiburg and its external partner institutions, including the EUCOR network, are outstandingly positioned for such a development. The Freiburg University has an internationally recognised research tradition in Life Sciences. Research consortia with an interdisciplinary focus have a long and successful tradition in Freiburg. In a recent commitment, ALU decided to found and support LIFENET, a vision for the future of Life Sciences and Biomedicine at the university. Accordingly, the interdisciplinary research focus for the next five years will defined by systems biology for the exploration of complex systems in biology and medicine. LIFENET particularly aims at networking the experimental and theoretical research disciplines at ALU, centered around BCCN (Bernstein Center for Computational Neurosciences) and ZBSA (Freiburg Center for Systems Biology). Cutting edge reseach will help to generate synergies that can lead to the development of new technologies and will further enhance the reputation and attractivity of interdisciplinary life science research. Both are prerequisites for attracting substantial future fundings from both public and private partners. Interactions between the experimental and theoretical groups are at the core of FRISBY. The idea is that, Life Scientists together with Mathematicians define the conceptual framework of a new series of experiments to define, prior to the execution, the hypotheses behind the research, the required inputs and the data standards in which the data can/will be recorded. Typically, this requires very intense interactions to guarantee the best possible data standard. At this point, local expertise from Microsystems Engineering and the Freiburg Fraunhofer Institutes will become very important, if novel technologies are required for data acquisition. Sophisticated high-throughput protein technologies should also be locally avaible through the interaction with SystemsX in Basel and Zurich (see LOI). Based on a first set of experiments, the theoretical scientist will develop a model that will serve as the basis for the definition of a next experimental setup. Reiterative rounds of this process will subsequently improve the quality of both data and experiment. FRISBY aims at developing Freiburg to become the leading center for systems biology in Germany. It is, together with Heidelberg (Bioquant), the center in Germany with an own research building dedicated exclusively to reseach in systems biology. Moreover, all contributing labs that group around ZBSA are within walking distance (less than 20 min by foot). The location of Freiburg at the borders to Switzerland and France, traditionally an infrastructural disadvantage, is advantageous for an international network in systems biology in the center of Europe. SystemsX, the Swiss Initiative on Systems Biology, is less than 40 min away in Basel, as are several of the world-class research centers (FMI, Biozentrum) and corporate research centers (Novartis, Roche) that share common interests with FRISBY. In France, the IGBMC, with which FRISBY currently negotiates both research collaborations, a shared seminar series in the EUCOR context, and multinational teaching of students and postdocs, is also less than one driving hour away from Freiburg. Taken together, FRISBY in Freiburg is strategically well positioned at the heart of European research in systems biology. Embedding systems biology in Freiburg: The University of Freiburg is exceptionally positioned for all three aspects of systems biology research, Life Sciences, Theoretical Sciences including informatics, and Engineering. Kapitel 2 Baumeister 2 High-profile researchers contributing to FRISBY have acquired an international reputation for experimental research areas in the Life Sciences, including plant biotechnology (Arabidopsis, genome of Physcomitrella), animal models for development and disease (C. elegans, Zebrafish), as well as cellular and cell and tissue model to analyze specific aspects of signalling and regulation. Both top-down (starting with a disease state) ad bottom-up (beginning with genes and proteins) approaches are being used in these models. Several of the models can be scaled up to allow large-scale analysis, and are amenable to high-throughput techniques. In its recent proposal to develop a institutional vision for the future of the university (for the national initiative of excellence, track III), ALU has made a remarkable commitment towards developing systems biology into the major focus of future development in the Life Sciences. In its concept LIFENET, the Life Science part of the Freiburg Institute for Advanced Studies, ALU developed a concept to support research in systems biology by dedicating the support money to five junior groups, tenure track, equipped competitively according to Max-Planck standards, to be housed at ZBSA. Microsystems technology is the youngest disciplines at Freiburg University and is involved in several research consortia that contribute to FRISBY. One of the goals of this technical discipline is the generation of nano-scale in vitro and in vivo environments required for certain analyses (e.g. microfluidics), for the development of micro- and nanosensors that allow intracellular measurements or low-volume analyses. One stronghold of the Life Sciences in Freiburg is the exquisite central imaging facility that collaborates with more than xx groups on a local and national level. In collaboration with pattern recognition software specialists at the Informatics department novel optical tools are currently generated to allow 4D analyses of expression patterns and automated phenotyping software (recognizing shape and mobility of an object = organism). Modeling of signaling pathway and statistical analyses (xxx Jens, bitte ausführen) is another level at which Freiburg scientists have excelled in the last years. The theoretical part of the first large-scale systems biology project funded in Germany, HepatoSys, is coordinated through members of FRISBY Freiburg. In addition, equally strong contributions to scientific discovery came from bioinformatic research at the faculties of Biology (Biologie II) and Informatics. The major focus here is on the annotation and interpretation of entire genomes and on developing tools for the prediction of nuclei acid structures and behaviors. Strong interactions exist in coupling experiments with computation and technology. A Research focus (Landesforschungsschwerpunkt) couples groups from Informatics, Medicine, Biology, and Microsystems technology for the exploration of novel bioimaging tools for biomedicine. Several groups involved in the FORSYS proposal are collaborators in this program (Palme, Driever, Baumeister). The framework and conceptual core of FRISBY will be the currently established research center ZBSA that was founded in 2005, together with the Bernstein Center for Computational Neuroscience (BCCN) as the result of two competitions of excellence (BMBF – Federal Ministery for Education and Research and State of Baden-Württemberg). In a major commitment, the University has offered to finance the organisational structure of ZBSA (financial director, secretary, network specialist, maintenance worker). In addition, the positions of the four head researchers of the core facilities are also secured for initially six years. A strong computational infrastructure has already been developed, and consists of several decentralized data acquisition systems, and a centralized database platform for the storage and Kapitel 2 Baumeister 3 retrieval of optical data and information of any kind. A LIMS (laboratory information managements system is currently set up through the help of a DFG WAP program awarded to the Biology Department in 2005. In order to facilitate the exchange and retrieval of experimental data, and as a platform for the use of quantitative data in a theoretical modelling approach, electronic lab notebooks (CONTUR ELN, Sweden) have been set up in individual test labs. FRISBY will bring together several of the ALU’s great strength, its competence in the Life Sciences (plant biotechnology, immunology, developmental biology and biomedicine) in the computational biology, and in technologies. All are prerequisites for the modelling ob dynamic biological systems. The chosen pilot projects all fall into the competence areas of contributing labs and establish a modelling platform for several steps of signal transduction between cells and their consecutive execution of intracellular regulatory pathways. They seamingless intercalate with one another, as may be exemplified here for one project: External information, e.g. in the form of hormones, secreted molecules and transmembrane proteins ZBSA is closely embedded into the tri-national research context of the region Oberrhein. Close relationship was already established with SystemsX, the Swiss Initiative in Systems Biology, and its BSSE – Basel Center for Biosystems Science and Engineering and its founding director, Prof. Henry Baltes. Tight interactions in research and teaching have already been negotiated with the director and the leading scientists of SystemsX, Prof. Renato Paro and Prof. Ruedi Aebersold, ETH Zurich. Additional support comes from the Imperial College, London, that recently was granted its CISBIC proposal (Center for Integrative Systems Biology at Imperial College) and its director, Dr. Young. ZBSA (Freiburg Center for Systems Biology) offers an interdisciplinary research environment hosting both experimental and theroretical scientists to analyse biological systems, their structures, behaviour and communications. Models developed during this process will be used for the prediction of structure-function relationships and for the simulation of experiments, whose execution is not possible, since they use living organisms and are ethically problematic, or turn out to be too cost-consuming. ZBSA is one of the first research centres of its kind in Germany. A new building will be available as of end of 2007 and will provide core facilities including Genomics, Proteomics, Metabolomics, Bioinformatics and a central Imaging facility. It will host a significant number of junior groups and will offer the use of its core facilities with high-throughput capacity for all participating groups. Current recruitments involve the position for head of administration, administrative secretary, network specialist, and the head scientists of the four core facilities. Based on the experiences with the extremely successful trinational study program Biotechnology (Daimler-Chrysler Prize 2003) FRISBY will first develop a multinational PhD program Systems Biology and a Masters Study Program in Systems Biology. FRISBY connects its scientific concepts closely with FDM (Freiburg Zentrum für Datenanalyse und Modellbildung, the xxx hier fehlt noch was. Kapitel 2 Baumeister 4 Research environment: FRISBY aims at developing experimental and theoretical tools for improving our understanding of cellular communications, interactions and regulatory feedback at the supracellular levels. For this ambitious goal, Freiburg is well-positioned, with a large number of contributing laboratories in biology (plant biotechnology, animal models, biomedicine), medicine (molecular medicine), informatics (pattern recognition, systems theory), mathematics and physics (xxx Jens), and Microsystems technology (nanosensors, microfluidics, optical sensors). In addition to the central institute that will incorporate systems biology research at all levels (ZBSA), contributing laboratories and institutes are in close proximity, which greatly facilitates research exchange and data sharing. Moreover, the major contributing research units are already connected by software for datamanagement, including ImageAccess (data and image acquisition, storage and retrieval), Genedata (xxx da weiss ich nichts zu), and xxx