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Biotechnology Centre, Technische Universität Dresden (TUD)
Role in the project: The main tasks of this participant will be to manage and coordinate the project, and to conduct most parts of the computational analysis. The Beyer group will devise computational methods for the low- and high-level analysis of QTL data; it will create interaction networks for S. pombe and use those networks for integrating the QTL data and finally predict regulatory pathways relevant for understanding transcriptional and posttranscriptional stress response in fission yeast.
Groupleader: Andreas Beyer is heading the research group Systems Biology – Cellular Networks at the BIOTEC. He envisioned the PhenOxiGEn project and he will be the main scientific coordinator. Dr. Beyer is a member of the CRTD and co-organizer of the German Conference on Bioinformatics in 2008 (www.gcb2008.de). During his career Dr. Beyer coordinated six research projects involving research groups in five different countries. He is currently coordinating several other national and international projects. Andreas Beyer is a pioneer for the computational analysis of posttranscriptional regulation in yeast and he developed innovative methods for the integration of data in order to predict transcriptional regulatory networks. In collaboration with Trey Ideker (UC San Diego, U.S.A.) he developed approaches for the integrated analysis of genetic and physical interaction data. Currently, Dr. Beyer is working with Gerd Kempermann (CRTD) and with Andrew Su (GNF, La Jolla, U.S.A.) on novel methods for mapping mammalian QTL data onto protein interaction networks. Further, Dr. Beyer developed the eQED algorithm, which allows for a comprehensive analysis of transcriptional regulatory processes using eQTL data. All of these lines of research feed into the PhenOxiGEn project and they form a unique methodological basis for the innovations envisioned in this project.
University College London (UCL)
Role in the project: This participant will create the fission yeast strains for the QTL library and for all interaction experiments. Participant 5 will also lead the phenotyping of fission yeast strains and will be heavily involved in all microarray applications (expression arrays and ChIP-Chip). In close communication with Participant 1, this participant will also perform most wet-lab experiments to provide a variety of interaction data supporting the modelling efforts, and in turn will then perform a range of experiments to test and refine the modelling.
Participating scientists: Jürg Bähler has used fission yeast as a model eukaryote throughout his career. He has established a productive research programme and is leading genomic research in the fission yeast community. Bähler has recently been appointed as Chair in Cellular Systems Biology at UCL. The group uses genetic and genome-wide approaches to study gene regulation during cell proliferation and differentiation, and in response to unfavourable environmental conditions. This research has been published and highly cited in leading journals, resulting in more than 60 publications in the last 6 years. Bähler has invested considerable effort in making the microarray technology available to the wider community through several complementary joint projects. He has been collaborating with some 50 groups from 16 countries. The large-scale data sets on global gene expression control also provide a valuable resource and basis for future discoveries. These data are available from and are widely used by colleagues as a basis for follow-up studies. The substantial expertise in fission yeast biology and global approaches provided by the Bähler laboratory will help to effectively pursue the proposed research.
Center for Biological Sequence Analysis (CBS),
Technical University of Denmark
Role in the project: The main tasks of this participant will be to perform half of the genotyping and gene expression microarray analysis in conjunction with Partner 2. In addition, the Workman group will establish a pipeline to perform the primary microarray normalization and analysis. In addition, this participant will integrate data from the various analyses and perform the preliminary association studies between QTLs and differentially expressed genes (mRNA or proteins).
Groupleader: Christopher Workman is associate professor at the CBS Regulatory Genomics group. Dr. Workman has nine years of combined biotech industry and post-graduate experience. This includes three years of postdoctoral training in a leading Systems Biology lab at the University of California, San Diego headed by Dr. Trey Ideker. During this period he led a project that resulted in a map of transcriptional regulatory pathways that control the DNA damage response in yeast and a first author publication in Science. Dr. Workman has developed a number of bioinformatic tools and analysis methods that support research in transcriptional regulation. He has extensive experience analyzing gene expression microarray data from almost all technology platforms. In particular, he has pioneered improved methods of Affymetrix probe-level data analysis and has contributed to the widely used Bioconductor project. He has also contributed as a developer for the Cytoscape open source project.
Eidgenössische Technische Hochschule Zürich (ETH-Z)
Role in the project: The main tasks of this participant will be to conduct proteomics analyses. The Aebersold group will first apply a suite of state-of-the-art peptide and protein fractionation techniques and mass spectrometry methods to generate a library of measurable peptides in S. Pombe (PeptideAtlas); second, the collected information and expertise will be used to design and validate a set MRM assays for a list of stress-responsive proteins; third, all target proteins will be quantitatively screened by scheduled MRM across all QTL strains and under normal and stress conditions.
Groupleader: Rudolf Aebersold is heading the Institute of Molecular Systems Biology. His group has truly pioneered the field of proteomics and a number of approaches developed in the group are now broadly used as standards in proteomics. Among them, the implementation of alternative proteomics strategies to gel-based techniques; the use of Isotope-Coded Affinity Tags (ICAT) to differentially quantify changes in protein expression; the approaches for selective enrichment of subsets of peptides from a complex mixture; the development and benchmarking of techniques for phosphopeptide isolation and quantitative mapping; the development of quantitative approaches to analyze protein-protein interactions; a wide variety of proteomics data mining tools, including a complete pipeline for data analysis and statistical validation of proteomics result, as well as tools and procedures for data standardization and sharing at community level.
Recently, the Aebersold group pioneered the proposal that a fundamentally new approach to proteomics is required, especially if repeat analyses of differently perturbed proteomes are necessary, such as in systems biology research. The group proposed and started to implement a new approach, which will be developed and extensively applied in the proposed project.