Objective "Perturbations in cellular redox status are implicated in many human diseases, yet there is an extreme lack of knowledge about the effects of oxidative stress in vivo, mainly due to difficulties in measuring reactive oxygen species (ROS) in vivo and the absence of experimental models. REDOX will use novel transgenic technologies to develop mouse models that report on ROS in vivo, allowing spatio-temporal monitoring of different types of oxidative stress, ultimately simultaneously in a complex reporter line, and clarifying its role in the aetiology of disease and pathways of drug & chemical toxicity. These models will reveal oxidative stress as a primary cause, or a consequence, of the disease process. Reporters will be driven by endogenous genes regulated by different forms of oxidative stress and, uniquely, we will exploit the sophisticated redox sensing systems in bacteria to discern different types of ROS. In a sophisticated system we will express 3 reporters from the same stress regulated promotor, generating a polycistronic mRNA by use of the FMDV 2A sequence, which cleaves the nascent polypeptide to yield the endogenous gene product and individual reporters. LacZ will be used as an in situ reporter, luciferase for imaging, and a secreted protein, eg hCG, as a non-invasive biomarker in blood or urine. The in vivo role of oxidative stress in disease aetiology, and the potential of novel anti-oxidants to prevent such diseases, will be evaluated in these models. A further novel aspect will be to generate ES cells from the reporter lines, and create genetically-driven disease models which reflect inherited human diseases. REDOX combines ambitious experimental systems with sophisticated novel technologies to create models to define the role of oxidative stress in human disease, offering a new approach in defining and testing of disease prevention and therapeutic interventions while reducing the number of animals required." Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2011-ADG_20110310 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution UNIVERSITY OF DUNDEE EU contribution € 2 486 524,00 Address Nethergate DD1 4HN Dundee United Kingdom See on map Region Scotland Eastern Scotland Angus and Dundee City Activity type Higher or Secondary Education Establishments Administrative Contact Kathryn Williamson (Dr.) Principal investigator Charles Roland Wolf (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITY OF DUNDEE United Kingdom EU contribution € 2 486 524,00 Address Nethergate DD1 4HN Dundee See on map Region Scotland Eastern Scotland Angus and Dundee City Activity type Higher or Secondary Education Establishments Administrative Contact Kathryn Williamson (Dr.) Principal investigator Charles Roland Wolf (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
