Objective Cellular protection against oxidative damage is relevant to ageing and numerous complex diseases. We plan to use fission yeast as a model organism to gain a systems-level understanding of the oxidative stress response and obtain insights into the interplay of variable genotype, phenotype, and environment. To this end, the four participants will pursue a range of multi-disciplinary and complementing approaches that will be integrated with innovative computational methods for a unified view of a complete regulatory system. We will create a genetically and phenotypically diverse library of yeast strains from crosses of three independent parental strains with distinct stress sensitivities. The parental and segregant strains will be genotyped and phenotyped (in stressed and unstressed cells) using state-of-the-art sequencing, tiling array, and proteomics approaches, thus providing a rich basis for genome-wide association studies and computational modelling. Genetic, functional genomic, and proteomic approaches, along with computational methods, will be applied in parallel to develop protein and gene interaction networks that will further support the modelling efforts. Predictions based on the modelling will be validated with targeted wet-lab experiments to test and refine the mathematical models. Intimate inter-dependency between experimental and bioinformatic approaches based on close collaboration among participants with different expertise will be vital to develop successful models predicting the regulatory response to oxidative stress. The relative simplicity of yeast cells, which can be grown under tightly controlled conditions and with defined genetic and environmental perturbations, promises a thorough and deep understanding of the oxidative stress response system. Concepts developed in the proposed study will provide a valuable framework for research into more complex systems such as response networks and association studies in human cells. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencescomputer and information sciencescomputational sciencenatural sciencesmathematicsapplied mathematicsmathematical model Keywords oxidative stress pathway modelling posttranscriptional regulation quantitative trait loci Programme(s) FP7-HEALTH - Specific Programme "Cooperation": Health Topic(s) HEALTH-2007-2.1.2-5 - Multidisciplinary fundamental genomics and molecular biology approaches to study basic biological processes relevant to health and diseases HEALTH-2007-3.1-4 - Improving clinical decision making Call for proposal FP7-HEALTH-2007-B See other projects for this call Funding Scheme CP-FP - Small or medium-scale focused research project Coordinator TECHNISCHE UNIVERSITAET DRESDEN EU contribution € 640 100,00 Address Helmholtzstrasse 10 01069 Dresden Germany See on map Region Sachsen Dresden Dresden, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Sven Kreigenfeld (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all DANMARKS TEKNISKE UNIVERSITET Denmark EU contribution € 544 960,00 Address Anker engelunds vej 101 2800 Kongens lyngby See on map Region Danmark Hovedstaden Københavns omegn Activity type Higher or Secondary Education Establishments Administrative Contact Ernst Løwe Lindberg (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Switzerland EU contribution € 339 800,00 Address Raemistrasse 101 8092 Zuerich See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Administrative Contact Rudolf Aebersold (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSITY COLLEGE LONDON EU contribution € 950 600,00 Address Gower street WC1E 6BT London See on map Activity type Higher or Secondary Education Establishments Administrative Contact Kent Lee (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data