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ARC ProjectTitle: "Integrating experimental and theoretical approaches to decipher the molecular networks of nitrogen utilisation in yeast"Partner: Funding: Communauté Française de Belgique Project number: 04-09/307 Duration: 2004-2009 Project overview: The yeast Saccharomyces cerevisiae is the model living organism that has been by far the most extensively used to develop the novel experimental methods of genomics and proteomics. Multiple facets of the metabolism of yeast cells have been explored using these approaches. In this project, we plan for the first time to monitor at whole-genome scale the response of yeast cells to supply conditions for a key nutrient of all cellular systems: nitrogen. Yeast cells will be grown under as wide a range of nitrogen supply conditions as possible (yeast can use up to thirty different compounds as sole nitrogen source) and the state of their transcriptome will be monitored using the DNA microarray method. In parallel, the concentration of nitrogen-containing metabolites in the cell will be measured. The specific binding of key transcriptional regulators to their multiple gene targets will also be monitored under various nitrogen supply conditions. The numerical data thus generated will be interpreted by combining statistical (clustering, supervised classification, time series prediction), static (graph theory), and dynamic modelling methods. Novel hypotheses resulting from these in numero analyses will then be subjected to validation tests using classical methods of molecular genetics. Thanks to this permanent cross-feeding between experimental and theoretical analyses, the project aims to progressively decipher the complete molecular network of nitrogen metabolism in yeast, of its regulation, and of anticipated overlaps between this network and other domains of cell activity. The suspected dominant role played by membrane nutrient transport and sensing systems in the orchestration of this network will also be investigated. The project will be conducted by four research teams (as shown below), including biologists with expertise in genomics applied to yeast (B. André), computer scientists (G. Bontempi), bioinformaticians (J. van Helden) and biomathematicians (M. Kaufman). Beyond its scientific objectives, this project offers the exceptional opportunity to gather around a specific biological question the different competences which today appear absolutely essential to exploiting optimally the huge flows of biological data issued from the growing number of investigations based on genomics and proteomics. Research teams:
Kevin Kontos |
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